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Drug-Food Interactions in The Era of Molecular Big Data, Machine Intelligence,

and Personalized Health

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DOI: 10.2174/2212798412666220620104809

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Recent Patents on Food, Nutrition & Agriculture, XXXX, XX, 1-13 1

REVIEW ARTICLE

Drug-food Interactions in the Era of Molecular Big Data, Machine Intelli-

gence, and Personalized Health
Romy Roy1, Shamsudheen Marakkar1, Munawar Peringadi Vayalil1, Alisha Shahanaz1,2, Athira
Panicker Anil1,3, Shameer Kunnathpeedikayil1,4, Ishaan Rawal1, Kavya Shetty1, Zahrah Shameer5,
Saraswathi Sathees1,6, Adarsh Pooradan Prasannakumar1, Oommen Kaleeckal Mathew7, Laksh-
minarayanan Subramanian8, Khader Shameer9,* and Kamlesh K. Yadav10,11,*

re
1
Molecular Robotics, Cochin, Kerala, India; 2Sanaria Inc, Rockville, MD, USA; 3Mar Athanasious College for Ad-

he
vanced Studies, Tiruvalla, India; 4Thiruvalla, Kerala; People Care Health LLP Thrissur, Kerala, India; 5Urbana Mid-
dle School, Urbana, MD 21754, USA; 6University of Washington Seattle, Washington WA, USA; 7Indian Institute of In-

yw
formation Technology (IIIT), Kottayam, Kerala, India; 8Department of Computer Science, Courant Institute of Mathemat-

ly
ical Sciences, New York University, New York, NY, USA; 9Northwell Health, New York, NY, USA and Faculty of Medi-

an
cine, Imperial College London, London, UK; 10School of Engineering Medicine, and 11Department of Translational

on
Medical Sciences, Center for Genomic and Precision Medicine, Texas A&M University, Houston, TX 77030, USA

or
e
Abstract: The drug-food interaction brings forth changes in the clinical effects of drugs. While

us

ne
favourable interactions bring positive clinical outcomes, unfavourable interactions may lead to
toxicity. This article reviews the impact of food intake on drug-food interactions, the clinical ef-

yo
e
fects of drugs, and the effect of drug-food in correlation with diet and precision medicine.
at
A R T I C L E H I S T O R Y Emerging areas in drug-food interactions are the food-genome interface (nutrigenomics) and nu-

an
trigenetics. Understanding the molecular basis of food ingredients, including genomic sequenc-
iv

Received: December 23, 2021 ing and pharmacological implications of food molecules, helps to reduce the impact of drug-food
pr

Revised: March 4, 2022

to
Accepted: March 30, 2022 interactions. Various strategies are being leveraged to alleviate drug-food interactions; measures
including patient engagement, digital health, approaches involving machine intelligence, and big
al

ed

DOI:
10.2174/2212798412666220620104809 data are a few of them. Furthermore, delineating the molecular communications across diet-
on

microbiome-drug-food-drug interactions in a pharmacomicrobiome framework may also play a

ad

vital role in personalized nutrition. Determining nutrient-gene interactions aids in making nutri-
rs

tion deeply personalized and helps mitigate unwanted drug-food interactions, chronic diseases,
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and adverse events from their onset. Translational bioinformatics approaches could play an es-
pe

sential role in the next generation of drug-food interaction research. In this landscape review, we
up

discuss important tools, databases, and approaches along with key challenges and opportunities
in drug-food interaction and its immediate impact on precision medicine.
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Keywords: Drug-food interactions, nutrigenomics, precision medicine, machine intelligence, big data, pharmacomicrobiome.
ed

1. INTRODUCTION ease with which data on drug-drug interactions is readily

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available, information on drug-food interactions is often

Many medicines contain potent substances that interact
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challenging to obtain as humans consume a variety of food

inside our system in various ways. Lifestyle and diets have a
that could interact with drugs. Accurately determining the
significant impact on how medications work. A drug inter-
st

effects of diet and nutrition on a drug is challenging and

action eventuates when a substance alters the properties of a complex. This article is intended to assist professionals in
di

drug, causing the effects to be increased or lessened or pro-

healthcare and patients in acquiring more knowledge about
ducing results that neither of the drugs or food could cause
drug and food interactions. The relationship between food,
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on its own. Common types of interaction involve drug-drug

nutrition, and health is complex and multilayered. Everyone
interactions and drug-food interactions. These can happen
needs food to survive; being healthy is synonymous with
due to unintentional misuse or lack of awareness about the
ot

survival. The food we eat is one of the vital contributing

active components in the substances [1-7]. Contrary to the factors to being healthy (Fig. 1). Consuming too much food
N

or consuming too little food affects our nutritional level and

*Address correspondence to these authors at the Northwell Health, New York,
NY, USA and Faculty of Medicine, Imperial College London, London, UK;
E-mail: skhadar@gmail.com (Khader Shameer); Department of Translational
Medical Sciences, Center for Genomic and Precision Medicine, Texas
A&M University, Houston, TX 77030, USA;
E-mail: kamlesh.k.kadav@gmail.com (Kamlesh K. Yadav)
can result in adverse health consequences; optimal nutrition
can be achieved with the right type of food [8]. Translation-
al bioinformatics could play a critical role in understanding
the molecular players, interactions, and the impact of food
on medicine. FDA categorizes drug interactions into three

2212-7984/XX $65.00+.00 © XXXX Bentham Science Publishers

2 Recent Patents on Food, Nutrition & Agriculture, XXXX, Vol. XX, No. X Roy et al.

broad categories (drug-drug interactions, drug- sors and supporting nutrients to enhance membrane and
food/beverage interactions, and drug-disease interactions). synaptic formation and function in Alzheimer's disease. Da-
The inverse term “food-drug interactions” is also used in the ta from a randomized clinical trial showed improvement in
literature to define the same concept. However, in this re- the function of verbal recall [11].
view, we focus exclusively on drug-food interactions; other
interaction themes are out of scope. 2.3. Diet Food
Any food whose recipes are reformulated/restructured to
reduce fat, carbohydrates, or sugar, making it part of a diet
for a specific function like slimming or bodybuilding, is
called diet food [12].

2.4. Functional Food

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Functional food is natural or processed foods containing
known or unknown biologically active compounds, provid-

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ing a scientifically validated and recorded health benefit for
the prevention, management, or treatment of chronic diseas-

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es in specified, safe, non-toxic quantities [13].

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3. WHAT IS MEDICINE?

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Any synthetic or organic substance that aids in preven-

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tion, diagnosis, treatment, healing, and health promotion is

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medicine. Since ancient times, food has played a vital role

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in preventing and treating diseases. Hippocrates, the father
of modern medicine, once said, "Let food be your best med-

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Fig. (1). Different aspects that encompass optimal health. (A high- icine and your best medicine be your food" [14].
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er resolution / colour version of this figure is available in the elec-

an
tronic copy of the article). 3.1. Food as Medicine
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Since time immemorial, the role of nutritious and

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2. WHAT IS FOOD?
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healthy food in maintaining health has been well acknowl-
Food is any substance when ingested and digested sati- edged. Recent studies show that food can prevent chronic
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ates hunger by providing nutrition without any immediately diseases and metabolic syndromes like obesity, diabetes,
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noticeable harm [9]. The food we consume sustains life by hypertension, and dyslipidemia [14, 15]. Dietary risk factors
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supplying energy via nutrients and prompts the organism's were responsible for 11 million deaths and 255 million disa-
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growth. Plants and animals are two principal sources of bility-adjusted life years in 2017. Systematic evaluation of
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food; while each source has its distinctive merits and demer- dietary consumption patterns provides a comprehensive
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its, it is beneficial to consume food from both sources than picture of the health effects of poor dietary habits. Dietary
relying on a single source. The food can be divided into four risks affect people regardless of age, sex, and other socio-
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groups as defined below: healthy food, medical food, diet demographic characteristics. Improvement of diet could
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food, and functional food. potentially prevent one in every five deaths globally.
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2.1. Healthy Food 3.2. Food and Disease

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Healthy foods are broad classes of food that supply the Food availability and individualized diet play a critical
body with vital nutrition and adequate calories. Although role in defining long-term health outcomes. Here we briefly
rib

healthy foods can be obtained from animal and plant discuss the role of food in the setting of three crucial diseas-
sources, they are predominantly plant-based whole food es.
st

with little to no processing. Eating healthy food comple-

3.2.1. Cardiovascular Diseases
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mented by a healthy lifestyle decreases the risk of many

chronic diseases [10]. Cardiovascular disease is ranked as the number one
be

cause of death worldwide [15]. The high prevalence of car-

2.2. Medical Food diovascular disease in this century can be undeniably linked
to poor food choices and unhealthy lifestyles. Dispropor-
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Medical food comes under distinct categories intended

and formulated for unique disease management, metabolic tionate consumption of nutritionally low but calorically
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deficiencies elicited from scientific principles and medical
assessment. For example, Axona and Souvenaid are two
medical foods for Alzheimer's disease and memory impair-
ment. Axona provides neurons with an alternative source of
energy to glucose, the β-hydroxybutyrate ketone. The ran-
domized phase II clinical trial showed significant improve-
ments in cognitive performance. Souvenaid contains precur-
dense foods results in systemic inflammation, changes in
insulin sensitivity, poor glucose regulation, and metabolic
abnormalities [16]. Consumption of functional food that has
cardioprotective properties, such as reducing homocysteine
levels, lipid-lowering effects, and antioxidant ability inte-
grated with lifestyle changes, can be widely utilized to pre-
vent cardiovascular diseases (Table 1) [17].
Drug-food Interactions in the Era of Molecular Big Data Recent Patents on Food, Nutrition & Agriculture, XXXX, Vol. XX, No. X 3

Table 1. Functional foods and their protective cardiovascular properties.

Functional Food Bioactive Compounds Mode of Action

α-tocopherol inhibits the oxidation of low-density lipoprotein cholesterol. α-tocopherol shows

Nuts Tocopherols anti-inflammatory activity and modulates the expression of proteins involved in the uptake,
transport, and degradation of atherogenic lipids [18].
Soy proteins Genistein and daidzein Reverse stress-induced alteration of protein expression profile in postmenopausal women [19].
Improve anti-oxidant capacity, mitochondrial function, and autophagy while reducing oxidative
Extravirgin olive
Polyphenolics and oleic acid stress, inflammation, and cellular senescence in vascular smooth muscle cells (VSMCs) and
oil
endothelial cells (ECs) [20].
Citrus fruits Ascorbic acid Vitamin C intake is inversely associated with cardiovascular mortality [21].

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Anthocyanins, catechins, cya-
Grapes and red Prevent cardiovascular health problems through bio-efficacy on vascular parameters, myocardi-

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nidings, flavonols,
wines al conditions, and metabolism [22].
myricetin, and quercetin

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Table 2. Functional food’s role in cancer prevention.

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Bioactive Compound Functional Food Medicinal Properties

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Phyto-estrogens Soya foods Anti-tumor [37]

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Flavonoids Plants

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Anti-oxidant [38]

Omega-3 Fish Anti-inflammatory [39]

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Fiber Vegetable and cereals Antitumor [40]
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Isothiocyanates Broccoli, cauliflower, kale Anti-tumor [41]
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Astaxanthin Green algae, salmon Antioxidant [42]

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Fucoxanthin Brown algae, heterokonts Anti-tumor [43]
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Lutein Dark green leafy vegetables Anti-tumor [44]

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3.2.2. Diabetes a chemo-preventive factor. The root stimulus for cancer is

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DNA damage, especially by free radicals. Functional foods

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Diabetes Mellitus type 2 is one of the fast-growing pub-

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have proven to reduce oxidative damage and oxidant stress

lic health problems globally; the relative treatment difficulty cell division, which is directly associated with mutagenesis
makes it expensive to manage. The food we consume plays
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and carcinogenesis (Table 2) [34-44].

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a crucial role in preventing and managing diabetes. Func-

tional foods, especially derived from plants containing fla- 4. BIOAVAILABILITY, BIO-ACCESSIBILITY, AND
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vonoids, polyphenols, sterols, unsaturated fatty acids, alka- BIOACTIVITY

loids, terpenoids, and sterols, can play a vital role in prevent-
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ing and managing type 2 diabetes. Studies have shown an The bioavailability of a nutrient is the percentage of nu-
inverse relationship between plant-based food and the occur- trients absorbed through the diet and used for normal body
rib

rence of type 2 diabetes[23,24]. The phenolics component, a function. The bioavailability of nutrients is associated with
secondary metabolite of plants, has been found to play a role both external and internal factors. The external factors in-
st

in preventing chronic diseases, such as type 2 diabetes. The clude the food composition and the structure of the nutrient.
di

mechanism is thought to be robust, as the phenolic molecule Age, gender, etc., constitute the internal factors [45]. The
present aids in the suppression of oxidative stress and in- essential step in making a nutrient bioavailable is to eman-
be

flammation. The phenolic compounds also activate the cipate the nutrient from its food matrix and transform it into
erythroid 2-related factor (Nrf2) pathway, which increases the the chemical form that can bind. The existence of nutri-
expression of ARE (antioxidant response element), resulting ents/minerals in different chemical structures can influence
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in increased concentrations of free radical scavengers. Poly- their bioavailability. Dietary iron exists in two forms, haem-
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phenols also influence carbohydrate metabolism, insulin sen-
sitivity, and inflammation mediators [25-29].
3.2.3. Cancer
A staggering 30 % of all cancer incidence can be directly
or indirectly linked to nutrition and food [30-33]. Several
naturally occurring compounds in plants or plant extracts
have exhibited anti-cancerous properties and their ability as
iron and non-haem forms of iron. The iron from the haem-
iron form is readily and easily absorbed by our body, contra-
ry to the non-haem form, as the haem acts as a protective
ring around the iron atom once released from the food ma-
trix. The haem iron form is exclusively found from animal
sources, whereas non-haem iron can be obtained from ani-
mal and plant sources [46, 47].
4 Recent Patents on Food, Nutrition & Agriculture, XXXX, Vol. XX, No. X Roy et al.

Bioavailability is interrelated with two other terms, bio-
accessibility and bioactivity (Fig. 2). Bioaccessibility is the
number of nutrients liberated from the food matrix, detecta-
ble in the gut, and passing through the intestinal barrier.
Bioactivity is the effect brought upon by the nutrients that
exert changes in health status. Bioactivity measurement is
rooted in events occurring when a bioactive compound in-
teracts with the biomolecules; these interactions set off a
metabolite /signal or a response that modulates and intensi-
fies until the health benefit is achieved [48]. The bioavaila-
bility of nutrients can be enhanced or inhibited. At the ab-
sorption site, nutrients can either interact with each other or
with other dietary components or biomolecules, resulting in
ly impact the pharmacokinetics process in several ways. The
solutions and compounds of the drug will be affected by
food consumption, and the absorption may be delayed for
several hours [52].
5.1. Drug-food Interactions in a Clinical Setting
Drug-food interactions significantly influence the effica-
cy of drug treatment and the side-effect profiles of drugs.
The clinical care team must be well educated and aware of
the relationships and interactions between foods, their con-
stituent nutrients, and drugs for successful drug treatment.
When drugs enter the human body, they may cause drug-

re
induced conditions; some of the states are fatal and life-
a change of bioavailability. An enhancer increases bioavail-
threatening [53]. They pose severe risks to patients when

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ability, whereas the inhibitor decreases bioavailability. For
administered together with food. When Ciprofloxacin, an
example, adding fat/ oil to the meal improves the bioavaila-
antibiotic commonly prescribed to treat respiratory tract

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bility of carotenoids, as they are fat-soluble. Vitamin C en- infections, is applied concurrently with calcium-fortified
hances the absorption of iron 2-3 times [49]. The medicinal
orange juice, it reduces the bioavailability to 40% over time.

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properties of curcumin, an active compound in turmeric,

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It may harm patients with adverse outcomes, such as the
cannot be effectively utilized because of its extremely low

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development of antibiotic resistance. Additionally, when
bioavailability. Piperine, an alkaloid present in black pepper
ciprofloxacin is taken with dietary molecules contained in

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and long pepper, alters the pharmacokinetics of curcumin.
milk, it lowers the bioavailability and reduces the dissolu-

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The concomitant administration of piperine (20mg) in- tion efficiency compared to the consumption of ciprofloxa-

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ne
creased the bioavailability of curcumin by 2000%. The
cin with drinking water [6].
study revealed piperine enhanced serum concentration, ab-

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sorption, and bioavailability [50].
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5.2. Drug-food Interaction Types
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The scaling of drug-food interaction studies in its nas-
iv

cent stage is limited to ascertaining whether a meal would

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interfere with the bioavailability of a drug. Recent research

to
studies affirmed that drug-nutrient interactions could alter
the pharmacokinetics and pharmacodynamics of drugs (Fig.
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3) [54, 55]. Pharmacokinetics is the quantitative elucidation

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of drug dispositions that consists of absorption, metabolism,

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distribution, and excretion. In contrast, pharmacodynamics

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refers to the clinical effects, which can be either a decrease

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in bioavailability or an increase in bioavailability, both of

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which can result in toxicities [54, 55]. There are mainly four
types of drug-nutrient interaction: Type I, Type II, Type III
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and Type IV.

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5.2.1. Type I
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Type I interactions happen even before the entry of

drugs and nutrients inside the body. It mainly occurs during
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the preparation formulation or administration process where

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Fig. (2). Interrelation between bioavailability, bioaccessibility, and the interacting elements directly contact each other. Patients
bioactivity. (A higher resolution / colour version of this figure is receiving parenteral or enteral nutrition are at greater risk of
st

available in the electronic copy of the article). type I interaction. Type I interaction is visible when you mix
drugs with food types. The drug Levothyroxine can interact
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5. DRUG-FOOD INTERACTION
during enteral nutrition, causing poor dissolution and possible
adsorption to the tubing, leading to hypothyroidism [56, 57].
be

Drug-food interactions are characterized as changes in

the pharmacokinetics or pharmacodynamics of a drug or 5.2.2. Type II
nutritional element and a reduction in nutritional status. Not
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all drugs interact with food items. A particular type of food Type II is the most common type of interaction, which
can trigger a range of interactions with drug mechanisms. occurs mainly when drugs and nutrients are administered
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These problems may range from slowing down the possible
drug effects to causing adverse effects on the body [1]. For
instance, the significant fluid volume would reduce the gas-
tric emptying rate of drugs ingested in specific forms of
human physical activity. Similarly, a large amount of solid
food consumption may reduce the gastric emptying rate of
drugs consumed [51]. The components of foods may direct-
orally or enterally. Type II can be further classified into
Type A, Type B, and Type C.
5.2.2.1. Type A
In this interaction, the enzymatic function is modified.
The altered enzymatic function increases the bioavailability
and may lead to toxicity. The cyclosporine and grape juice
Drug-food Interactions in the Era of Molecular Big Data Recent Patents on Food, Nutrition & Agriculture, XXXX, Vol. XX, No. X 5

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Fig. (3). Possible physical, chemical and kinetic changes due to drug-nutrient food interaction. (A higher resolution / colour version of this
figure is available in the electronic copy of the article).
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interaction is a classic example of type A interaction. The 5.2.4. Type IV

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interaction inhibits intestinal CYP34A, causing increased

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Tissue-specific Type IV interaction occurs when drugs

bioavailability of cyclosporine. Clinically, the increase in
and nutrients compete to eliminate transporter proteins.
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the concentration of cyclosporine leads to toxicity [56, 57].

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Modulation, antagonism, and enterohepatic elimination are

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5.2.2.2. Type B some of the consequences of Type IV interaction [56, 57].

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Type B interactions are characterized by an altered 5.3. Food-drug Interaction: Experimental Studies
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transport protein function solely responsible for the

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Drug-food interactions may have two major clinical ef-

transport of agents before entering the systemic circulation,
fects: decreased bioavailability of a drug, which raises the
resulting in malabsorption of dietary components. The inter-
ed

likelihood of adverse effects, or increased bioavailability,

action of valproic acid found in berries and L-carnitine leads
which predisposes to treatment failure.[58] Bioavailability is
to competitive inhibition of the transport protein SLC22A
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an important pharmacokinetic parameter correlated with the

resulting in malabsorption of dietary carnitine. [56,57]
clinical outcome of most drugs.[59] Drug transporters and
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5.2.2.3. Type C drug-metabolizing enzymes play essential roles in drug in-

gestion, delivery, digestion, and elimination. The pharma-
st

Type C interaction is characterized by chelation, bind- cokinetics and pharmacodynamics of medication may be
ing, or complexation of drug and dietary components, lead-
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affected by individual or combined actions. One of the con-

ing to deactivation or reduced bioavailability. Ciprofloxacin
founding factors that have recently been shown to lead to
and calcium supplements form complexes of Ciprofloxacin
be

possible complex drug interactions is the interaction be-

with calcium ions resulting in reduced bioavailability of
tween drug-metabolizing enzymes and transponders [60].
Ciprofloxacin [56,57].
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5.3.1. Food and Drug Transponders

5.2.3. Type III
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Drug transponders in the gut and liver regulate absorp-

Type III interactions involve changing the volume of
distribution of cells or tissues, changes in metabolism, and
penetration to specific tissues or organs. Type III interac-
tions can be reduced by adjusting the dosage to the optimum
amount. The interaction of rasagiline and tyramine in large
amounts causes an acute hypertensive attack referred to as
cheese reaction [56,57].
tion and bioavailability, which is critical in deciding oral
drug disposition. Many secondary metabolites known as
phytochemicals are present in everyday foods like fruits and
vegetables, and many have been linked to health benefits.
Recent studies show that some of the phytochemicals are
substrates and modulators of specific members of the super-
family of ABC transporting proteins [60].
6 Recent Patents on Food, Nutrition & Agriculture, XXXX, Vol. XX, No. X Roy et al.

Table 3. Fruits-drug interactions.

Fruit Phytochemicals Drug Interactions

Phenolic acids (tannins), flavonoids (including quercetin), glycosylated xanthones

Apple Fexofenadine [61].
(mangiferin), and saponins
Flavonoids, such as anthocyanidin (cyaniding and poenidin), and flavonols (querce- Warfarin, In vitro system Diclo-
Cranberry
tin) and carotenoids fenac [61, 62].
Calcium channel antagonist,central
Bergamottin, flavonoids (nobilein, tangeretin, quercetin, diosmin, naringenin, nar- nervous system modulators, HMG-
Grapefruit
ingin, and kaempferol), and furanocoumarins CoA reductase, immunosuppres-
sants, antibiotics [61, 63].
Midazolam, diclo-
Phenolic acids (tannins), flavonoids (anthocyanins), carotenoids, essential oils, fatty

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Mango fenac,chlorzoxazone, verapamil
acids, lectins, phenols, saponins, alkaloids, and triterpenes
[61, 64].

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Pomegranate Phenolic acids (punicalagin and tannins), flavonoids (anthocyanins), and pectin Carbamazepine [61, 65].

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Vinblastine, fexofena-
Naringin, limonin, flavonoids, hesperidin, limonene, carotenoids, iso hesperidin,
Seville orange dine,ciprofloxacin, ciclosporine
terpineol
[61, 66].

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Tangerine Flavonoids as diosmin, tangeritin, nobilein, and quercetin Nifedipine, Digoxina [61, 62, 67].

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Table 4. Vegetable-drug interactions.

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Vegetables Phytochemicals Drug Interactions
Flavonoids and p ‐coumaric acid derivatives, α‐lipoic acid, poly- In vitro system: heterocyclic aromatic

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Spinach
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phenols, lutein, zeaxanthin, betaine amines [68].
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Carotenoids phytofluene, phytoene, neurosporene, γ‐carotene, and

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Diethylnitrosamine, N-methyl-N-
Tomato ζ‐carotene lycopene, phytoene, phytofluene, quercetin, polyphe-
iv

nitrosourea and 1,2 dimethylhydrazine [69].

nols, kaempferol
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to
Phenylethyl isothiocyanate (PEITC) and methylsulphinyl alkyl
isothiocyanates (MEITCs), flavonoids such as quercetin, hy-
Watercress Chlorzoxazone [70].
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droxycinnamic acids, and carotenoids such as β‐carotene and

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lutein
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5.3.2. Food and Metabolizing Enzymes

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In general, drug metabolism reactions are divided into

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two stages. Phase I reactions (oxidation, reduction, and hy-

drolysis) are mainly regulated by the cytochrome P450
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(CYP) family of enzymes. Phase II reactions combine the

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drug or its phase I-derived metabolite with an endogenous

compound, such as glucuronic acid, glutathione, or sulphate,
ed

to create a more polar end-product that can be excreted more

easily (Tables 3 and 4) [61-70].
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5.3.3. Drug-food Interaction Network

rib

Knowledge of drug-food interactions aids to identify,

predict, and to prevent unfavourable interactions between
st

food and marketed or novel drugs [71]. To interpret the bio-

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logical responses to diet, as well as to assign the importance

of drug-food interaction, we need to assemble all available
be

information on the chemical background of the small mole-

cules in our diet. “NutriChem” is such a database that helps
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us estimate the effect of plant-based food on health based on

the availability of information related to the food's small
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molecule constituents [72]. Integrating the “NutriChem”
biological activity data of marketed drugs makes it possible
to study the effect of diet on drug properties related to their
pharmacokinetics and pharmacodynamics, and create drug-
food interaction networks that help the patients and clini-
cians easily understand the food items that must be poten-
tially avoided while under medication (Fig. 4) [72, 73].
Fig. (4). A network graph of Piperine the active component of
black pepper. Stronger associations are represented by thicker
lines. Protein-protein interactions are shown in grey, chemical-
protein interactions in green and interactions between chemicals in
red. (A higher resolution / colour version of this figure is available
in the electronic copy of the article).
Drug-food Interactions in the Era of Molecular Big Data Recent Patents on Food, Nutrition & Agriculture, XXXX, Vol. XX, No. X 7

The drug-food interaction network allows system-level
analysis in revealing the underlying mechanism behind the
drug-food interactions. A network is simply a graph with
nodes and edges. Nodes are entities that we evaluate, and
edges are the connections between them. Edges convey in-
formation about the linkage between the nodes [73]. We can
systematically visualize the interaction and its properties by
retrieving interaction data from “NutriChem” and construct-
ing different drug-food interaction networks. Drug-food-
target protein interaction networks are based on unique pro-
tein interactions shared between different foods, and they
can be made in different ways. One is a network of foods as
nodes that interact with the same drug target proteins.
understand it better. One such factor yet to be considered is
the amount of food and drugs. It is of much relevance as the
bioavailability of the drug has a major role in the pharmaco-
kinetic activity. Right drugs, along with the right food in the
right amount, are what we need. Quantified drug-food inter-
action networks can be considered as the key to this [71-74].
5.4. Medicines Exhibiting Poor Bioavailability in the
Presence of Food
Drug-food interactions can recklessly reduce or increase
the drug's impact. Some commonly used herbs, fruits, and
alcohol may cause treatment failure to a point affecting the

re
patient's health. Most clinically significant drug-food inter-
The node size reflects the number of phytochemicals, actions are triggered by changes in the drug's bioavailability

he
and the edge width represents the number of interacting pro- caused by food (Table 5) [75-80].
teins common to the two foods. Another way is by consider- 5.4.1. Pharmacomicrobiome: The Complex Relationship

yw
ing drug targets as nodes and connecting them when a min-
between Drugs and the Microbiome
imum number of foods having active interaction for both the

ly

an
drug targets are found. Although a given food can have ac- Gut microbiota may play a primary role in human health

on
tivity for drug targets of various disease categories, creating by affecting the immune response, intestinal homeostasis,
an individual network for each disease category is conven- nutrient processing, energy harvesting, and pathogen re-

or
ient [71-73]. Networks are also created based on drug-food sistance. An increase in the risk of various diseases, such as

e
interactions affecting pharmacodynamics or pharmacokinet- obesity, inflammatory bowel disease (IBD), cancer, diabe-

us

ne
ics. Phytochemicals in the diet interact with proteins within tes, psychiatric disorders, and asthma has been related to an
enzymes, transporters, and carriers other than drug targets. imbalance of the gut microbiota. [81] Many studies have

yo
e
These networks have drug targets or proteins within the rest proposed that the mechanism is bidirectional, suggesting
at
of the categories (enzymes, transporters, or carriers) as that the microbiome affects the drug and the microbiome.

an
nodes along with drugs and food are complex with multiple This hypothesis was tested in a clinical trial. Statins reduce
iv

factors considered at a time. It can be effectively dealt with circulating LDL by promoting the growth of gut bacteria
pr

to
by assigning different shapes to different nodes (circle= that produce bile salt hydrolases, enzymes that break down
protein target, triangle= drug, diamond=food) and various the bile acids to digest fatty foods. Gut microbes may con-
al

ed

edge colors for different phytochemicals. This helps in un- tribute to drug efficacy and protection by enzymatically
on

derstanding the activity of food more closely. Incorporating modifying drug structure and altering drug bioavailability,
ad

more factors into the drug-food interaction network helps to bioactivity, or toxicity [82]. Proton pump inhibitors, selec-
rs

lo

Table 5. Food-drug interactions.

pe

up

Drugs Food Mechanism

r
Fo

or

ACE Inhibitors Empty stomach Absorption is increased [75-78].

Acetaminophen Pectin Delays absorption [75-78].

ed

Celiprolol Orange juice The intestinal absorption is inhibited [75-78].

ut

Cycloserine High fat meals Decreases the serum concentration [75-78].

rib

Esomeprazole High-fat meal Decreases bioavailability [75-78].

st

Fexofenadine With grapefruit juice Reduces absorption [75-78].

di

Glimepiride with breakfast Absolute bioavailability [75-78].

be

Lanoxin With licorice Increases the risk of drug toxicity [75-78].

NSAIDS Alcohol Can increase the risk of liver damage or stomach bleeding [75-79].
ot

Penicillin Empty stomach Absorption is increased [75-78].

N

High protein diet, Vitamin

Tricyclics Reduce absorption of drugs [75-78]
C rich food

High-protein diet Raise serum albumin levels and decrease the international normalized ratio (INR). Interfere
with the effectiveness and safety of warfarin therapy. Decrease warfarin activity. Elevated
Warfarin Vegetables containing INR without bleeding in an elderly patient. Thromboembolic complications may develop,
vitamin k and hypoprothrombinemic effect of warfarin may be decreased [75-78, 80]
8 Recent Patents on Food, Nutrition & Agriculture, XXXX, Vol. XX, No. X
tive serotonin reuptake inhibitors, and laxatives are drugs
that affect the composition and function of the gut microbi-
ome. Changes in the gut microbiome caused by proton
pump inhibitors can decrease colonization resistance and the
development of enteric infections, such as Clostridium dif-
ficile infections.[83] Gut microbiome composition is associ-
ated with antitumor response and the clinical efficacy of
treatment with immune checkpoint inhibition. [81] Under-
standing how microbes and drugs interact may lead to new
therapies or improvements in administering current medica-
tions. For example, physicians may be able to predict how a
patient might respond to a drug based on their gut bacteria
and modify the patient's dosage accordingly. Dietary chang-
es or antibiotics might also be recommended to make a per-
son's gut microbiome more receptive to a drug.
6. STRATEGIES TO TRACK, MONITOR, AND
ALLEVIATE DRUG-FOOD INTERACTIONS
One of the primary barriers to avoiding drug-food inter-
action is the lack of readily available information. While
FDA and other regulatory agencies actively monitor such
or
interactions and include leaflet information as part of medi-
e
cation dispensing. The patients may not routinely refer to
us
ne
such information. Innovative approaches are now required
to remind patient communities of the potential risk of drug-
yo
e
food interactions routinely. Resources like DrugBank (See:
at
https://go.drugbank.com/drug-interaction-checker) and other
an
websites provide interaction checkers [84]. In the following
iv
section, we discuss key transdisciplinary approaches.
pr
to
6.1. The Emerging Role of Digital Health in Patient-
al
ed
reported Outcomes in the Setting of Drug-food Interac-
tion
on
ad
Digital health refers to the use of information technolo-
rs
gy, communication technologies, and electronic technolo-
lo
pe
gies for better healthcare delivery [85]. Digital health ame-
up
liorates computational technologies, smart devices, compu-
tational analysis techniques, and communication media to
r
Fo
or
help healthcare professionals and patients. The inception
and the rapid growth of digital health can be seen as parallel
ed
with the digital revolution because all enabling technologies
of digital health are the result of the digital revolution, such
ut
as mass production of digital circuits, microfabricated de-
vices, novel communication technologies, cellular phones,
rib
computers, and even the internet. It started in 1897 with
telemedicine when a child was diagnosed with croup cough
st
via the telephone [86]. It was the first remote diagnosis re-
di
ported. The introduction of the edge notched cards of the
early nineties, Hollerith punched card for electromagnetic
be
data tabulation and storage, completion, and installment of
ENIAC (Electronic Numerical Integrator and Computer),
ot
the first general-purpose digital computer at the University
of Pennsylvania, led to the development of the timeline [87].
N
Later, the rapid growth of digital health parallels technolog-
ical milestones, such as the invention of the point-contact
transistor, the first type of transistor to be successfully
demonstrated, at the Bell Laboratories in 1947, etc. [88].
Other milestones of digital health were the first implantable
cardiac pacemaker which itself was enabled by the devel-
opment of the transistor, the release of the first Holter moni-
Roy et al.
tor (cardiac activity monitor) in 1962 [89], the proposal of
relational database by E. F Codd in 1970 that set the stage
for large datasets, the introduction of the first automated
blood analyzer by Technicon in 1974, the first clinical CT
scanner in 1975, the introduction of the first generation
LIMS (Laboratory Information Management System) and
the introduction of user-friendly infusion pumps in 1982, the
introduction of the first wearable consumer wireless heart
rate monitor in 1983, the introduction of the first commer-
cial automated DNA sequencer in 1987 [90], home glucose
meter in 1987 which was one of the first commercial bio-
sensors, the introduction of the compact automatic wrist cuff
re
blood pressure monitor by Panasonic in 1993, the first chip-
based DNA sequencing technology in 1996, the launching
he
of the Da Vinci robotic surgical system and the Publication
of the "draft" map of the Human Genome in 2000 [91].
yw
Moreover, the formation of organizations, like Healthcare
Information and Management Systems Society (HiMSS) in
ly
an
1961, Health Level Seven International in 1987, American
on
Medical Informatics Association in 1989, Documentum
content management platform in 1990, The LOINC (Logical
Observation Identifiers Names and Codes) database in 1994,
and the Clinical Data Interchange Standards Consorti-
um(CDISC) in 1997, was game-changing [92]. The ele-
ments of digital health include wireless devices, sensor vari-
eties, advanced software technologies, the internet, social
networking, and other long and short-range networks. And
these technologies have helped the advancement and devel-
opment of prognosis, diagnosis, and treatment methods.
Digital health approaches in prognosis facilitated unprece-
dented growth in recent times. The availability of large
databanks or databases, the popularity, and advancement of
Electronic Health Records (EHR), and clinical data systems
help predict the future development of a disease, expectation
of the quality of life, probability of health issues, and com-
plications and likelihood of survival. Along with these tech-
nologies, advanced sensors to collect data, wearable devices
to monitor health status, and advanced algorithmic tech-
niques like statistics-based algorithms and neural network-
based algorithms helped forecast diseases and health condi-
tions [93]. Digital tools are used in diagnosis, such as
smartphone-based scanning devices, portable and highly
personalized diagnostic devices leveraging nanotechnology
and MEMS (Micro Electro Mechanical Systems), cheap and
advanced microfluidics systems like Lab on a Chip (LoC)
for rapid testing of body fluids. Recent innovations includ-
ing novel micro designs of diagnostic tools, biocompatible
and invasive sensors, ultra-thin and low power chips and
transistors, advanced low power, and high-efficiency sen-
sors, and nanotechnology-based point-of-care diagnosis are
adding fuel to the future of digital health [94, 95]. These
technologies help medical and healthcare professionals
make better informed decisions and facilitate the prevention
and early diagnosis of life-threatening diseases. From mo-
bile medical applications and software systems to artificial
intelligence and machine learning algorithms, digital tech-
nology has been a driving revolution in healthcare. This
convergence of people, information, technology, and con-
nectivity will change how we deal with prognosis, diagno-
sis, treatment, and healthcare delivery.
Drug-food Interactions in the Era of Molecular Big Data Recent Patents on Food, Nutrition & Agriculture, XXXX, Vol. XX, No. X 9

6.1.1. Leveraging Social Media Platforms to Improve
Drug-food Interaction Awareness and Monitoring
Social media plays a vital role in behavioural psycholo-
gy today. 3.8 billion people (that is 50% of the global popu-
lation) use social media as of Jan 2020, according to Hoot
suite social media statistics [96]. These digital platforms
could spread the need and importance of adhering to medi-
cation administration instructions. According to the Hoot
suite statistics, users spend around 2 hours per day on social
media. Many actions taken by people are based on their en-
gagement in these platforms. Therefore, different stakeholders
can communicate general awareness of drug-food interaction
ited by Utilization Review Accreditation Commission
(URAC) and HONcode. The drug interaction checker option
on WebMD provides four types of interactions somewhat
similar to Medscape as 1. Do not use together, 2. Serious 3.
Monitor Closely and 4. Minor. A minimum of two com-
pared drugs/food has to be entered to get the interaction
information, unlike Drugs.com. It is available on iOS and
android with a rating of 4.6 and 4.5, respectively.[99]
6.2.4. BH Glove: Monitoring Drug-food Interaction using
a Wearable Device-app Integration
While there are multiple wearable devices, apps, and
monitoring services available to monitor food intake and get

re
through these platforms. Patients can also be provided with
a quantified view of an individual’s calorie intake, no device
options to clarify their questions on the social media pages of

he
is available, to the best of our knowledge, that can passively
pharmacies. Pharmacy services can create loyal patient cus-
monitor food intake and alert the patient. In this context, a
tomers and add value to their business profile [96].

yw
new device model, a smart connected glove that can monitor
mechano-sensing of eating patterns, is proposed. The Bio-
6.2. Drug-food Interaction Platform for Checking Poten-

ly
Heart glove (BH Glove) is an open-filtered glove synced

an
tial Drug-food Interactions
with an app and integrates monitoring of multiple physio-

on
A reliable and user-friendly app to check potential inter- logical parameters, including heart rate, oxygen level, and

or
actions with drugs will help pharmacists ensure vital drug blood pressure. Furthermore, the app integrated with the

e
information communication while filling prescriptions. glove can remind patients to take medications, and it noti-

us

ne
Even patients themselves could also check for any possible fies when patients need to condition. It tracks blood pressure
drug/food interaction and seek appropriate medical advice using data, as well as using unique trackers embedded in

yo
from their physician or pharmacists. We list the three most each finger. The blood pressure level is shape coded, and
e
reliable and user-friendly apps here. Furthermore, we dis- based on variability in blood pressure, the patient gets a noti-
at

an
cuss the design and system architecture of a wearable device fication on your phone from the app. The sensor on the back
iv

and companion app that could help track eating habits and of your hand can provide visual or voice indicators (lighting
pr

potential drug-food interaction patterns. up or making a chiming noise) to remind the patient to sleep
to
passively or actively, drink more water, exercise, or take their
6.2.1. Drugs.com
al

medicine. It can also intelligently track the motions of eating

ed

Drugs.com is a multipurpose platform for drug infor- certain things (junk food, vegetables, etc.) and tell the patient
on

mation. It hosts the disease, drug, FDA alert, drug compari- when to stop, or it can chime, reminding the patient not to
ad

son, pill identifier, and treatment guide. It provides provi- give in to the cravings. Patients can get healthier recipes from
rs

sions for Drug/Drug, Drug/Food, and Drug/Disease interac- the app and other alternatives on a companion phone applica-
lo
pe

tion. You can check all interactions concerning drugs by tion or web application. The app uses data from the glove and
up

typing the drug name in the search box, unlike other plat- personal preferences to make things such as a meal plan, a
forms where you have to write the comparison drug or food medication schedule, exercise routine, and other things. Pa-
r
Fo

to check whether they interact. It is available on iOS and tients also would get reminded that they cannot eat certain
or

Android platforms with a 4.4 and 4.7 rating, respectively. It foods or bring their pressure higher or lower. The companion
does not require any subscription like IBM, Micromedex or app can also track medicine, recognize food, retrieve content,
ed

Lexicomp. Drug.com is Health On Net (HONcode) certified and discuss potential drug-food interactions.
[97].
ut

6.3. Shared Decision Making

6.2.2. Medscape
rib

The patient-centric approach is vital to achieving the de-

Medscape is one of the widely used platforms by medi- sired therapeutic outcome, and thus it is a fundamental pillar
st

cal professionals to search for drug and disease-related in-

of clinical practice. A right therapeutic plan must be framed
formation. It provides in-depth drug information, including
di

based on patient preference coupled with evidence-based

dosing and pharmacokinetic parameters. It also has provi-
practice to ensure patient rights on ethical grounds [100].
be

sions for the latest medical news, CME, and other medical-
Physicians should seek an alternative based on the patient's
related courses. The drug interaction checker option in Med-
diet habits if those options can also lead to the desired out-
scape gives different levels of interaction from "Serious: come to a great extent. Providing different treatment options
ot

Use alternative," "Monitor closely," and "Minor."

and asking patients' preferences will help improve patient
N

Food/herbal interaction with grapefruit, green tea, garlic,

adherence to therapy and proactive involvement. Moreover,
ginger, etc., can be checked in Medscape. It is also available
patients are better informed in today's Google era than they
both on iOS and Android with a rating of 4.3 and 4.6, re-
were a few decades earlier. They appreciate if their concerns
spectively [98].
and preferences are considered in selecting appropriate
6.2.3. WebMD treatment regimens. Such a shared decision model will help
alleviate the untoward interaction of drugs with food or the
WebMD is another well-known online medical news and
patient's other nutrient intake [101].
information platform, especially for consumers. It is accred-
10 Recent Patents on Food, Nutrition & Agriculture, XXXX, Vol. XX, No. X
7. ROLE OF MACHINE INTELLIGENCE AND BIG
DATA IN PRECISION HEALTH
Machine intelligence and other artificial intelligence-
based technologies have helped the medical industry grow
to an unprecedented clinical and diagnostic advancement
level. Big data and machine learning have contributed main-
ly to prognosis and diagnosis [102]. Accurate forecasting of
diseases and conditions with time series prediction algo-
rithms and speedy diagnosis from image scanning using
advanced computer vision algorithms are some examples
[103]. Application-level Artificial Intelligence algorithms
are of two types, statistical mathematics-based algorithms
called machine learning algorithms and bioinspired neural
networked algorithms called deep learning algorithms. Tra-
ditional statistical methods and techniques enable easy han-
dling, analysis, processing, and decision making, using time
series data like clinical data. Statistical methods, such as
ARIMA, SARIMA, etc., were used earlier, and now most of
these prediction algorithms are replaced by efficient and better-
on
performing deep learning-based algorithms and techniques
or
[104]. Deep learning algorithms are designed to deal with time-
e
series data; data with time-based relations are called recurrent
us
ne
algorithms. A first of its kind is the Recurrent Neural Network
(RNN) that can process and make predictions on time series
yo
data, such as clinical data of lab measurements and DNA se-
e
quences. Advanced models of RNN such as LSTM (Long
at
an
Short-Term Memory) and GRU (Gated Recurrent Unit) have
iv
been helping computational biologists and bioinformatics engi-
pr
neers to make more accurate and fast predictions on medical
to
time series data [105]. This time series analysis and forecasting
al
process mainly helps in scenarios, such as cardiac arrest predic-
ed
tions in the ICU and patients' ECG records [104]. Big data and
on
large medical databases also play an important role. Big data is
ad
a vast quantity of data that may be of any sort, such as health
rs
records, which can be processed and analyzed by supporting
lo
pe
technologies. The most exciting feature of big data in
up
healthcare is that it can provide more precise and personalized
care. Big data analysis gives a detailed picture of patients and
r
Fo
or
even large populations with which healthcare practitioners can
determine how a particular patient will respond to a specific
ed
treatment or even identify at-risk patients before a health issue
arises [106].
ut
One of the main applications of big data is in predictive
rib
medicine and population health management. It helps in
patient prediction from population data and helps in better
st
staffing and staff shift management in ICUs, especially in
emergencies like a pandemic outbreak. Another application
di
of big data is on the HER (Electronic Health Records),
where every patient will have their digital record, including
be
demographics, medical history, allergies, laboratory test
results, etc. This can be used for analysis and forecasting
ot
[107]. To support this, several databases are also present,
such as the MIMIC critical care database. Another set of
N
algorithms and techniques are computer vision-based algo-
rithms that specifically deal with images and video. The
digital health scenario that deals with medical images and
videos has revolutionized the areas, like medical scanning
and diagnosis. It all started with the use of deep neural net-
works for visual applications, such as image classification
and recognition. Kunihiko Fukushima, in 1979, developed a
Roy et al.
dedicated network for this called neocognitron [108]. This
was followed by several visual-based algorithms, such as
CNN (Convolutional Neural Network), which is an inspira-
tion from the human brain's visual cortex, and LeNet by
Yann LeCun in 1998 [109].
These algorithms in the deep learning timeline have been
used in digital health and diagnosis, mainly in computer-
vision-based applications, such as image segmentation and
classification. Besides using mainstream deep learning algo-
rithms and techniques, researchers also developed dedicated
algorithms for medical images and videos [109, 110]. The
U-Net is an example; U-net comes from the autoencoder
re
family of deep learning algorithms and was developed
specifically for the segmentation of bio-medical images
he
such as brain scan images. It made the process of dealing
with multi-modal scan images easier, which was a com-
yw
plicated process earlier. It helped in speedy segmentation
of brain parts such as tumorous areas and helped in
ly
an
pathological diagnosis [111]. After this, many techniques
were introduced exclusively for biomedical applications,
like 3D U-Net and WNet. In the COVID-19 pandemic out-
break, these two subareas of deep learning have helped cli-
nicians and healthcare professionals worldwide, including
prediction, contact tracing of the viral infection, and diagno-
sis. Many international airports set up passenger screening
to identify people with elevated temperature levels, which is
a primary symptom of the disease. Many of the screening
systems include a thermal imaging camera along with a ded-
icated deep learning-based algorithm to detect people effi-
ciently [112].
Interaction between drugs and food includes but does not
restrict to the well-established domain of protein-protein
modeling. Hence, protein-protein interaction prediction
models can serve as the backbone for developing DFI (drug-
food constituent interactions) models [113]. The most com-
mon and regarded strategy, which has also been extended to
DFI, is Deep Learning. Deep Learning is a specialization of
Machine Learning (and hence, Artificial Intelligence) that
uses an architecture of neural networks, which automatically
extract the relevant features and predict the interaction out-
come. Features can be loosely thought of as (ideally) a min-
imal representation of the input used to train the network.
Since the Deep Learning paradigm is centered on automatic
identification and extraction of input features, it is generally
preferred over Machine Learning, which requires feature
engineering. Deep DDI (drug-drug interaction) is one of the
proposed models to predict Drug-Food Constituent Interac-
tion. The Deep DDI model is a multiclass classification
network that predicts the probabilities corresponding to each
of the 86 labels [114, 115]. However promising Deep DDI
may be, it still falls as a victim of the availability of DFI
datasets. Recently, Graph Embedding methods have shown
to be equally or more effective than the traditional neural
networks approach and are a field of interest, attracting
many researchers [116]. While it is important to develop
tools to predict drug-food interactions, it is equally im-
portant to find approaches for incorporating the DFI infor-
mation in the existing flow of information. Accessibility of
information and scalability of the information architecture
are important. With the rise of the digitization of healthcare,
the mass flow of information in medical scenarios and its
Drug-food Interactions in the Era of Molecular Big Data Recent Patents on Food, Nutrition & Agriculture, XXXX, Vol. XX, No. X 11

Table 6. Types of nutrient-gene interactions.

S. No. Type of Interactions Example

Direct interactions Vitamin A/vitamin A derivatives interact with receptor

1 In direct interaction upon contact with the receptor, the nutrients act as proteins of retinoic acid and activate or repress transcrip-
transcription factors that bind to DNA and induce gene expression. tion [119, 120].

Epigenetic modifications, such as methylation, acetyla-

Epigenetic interactions
tion, or biotinylation of histones lead to significant gene
2 In Epigenetic interaction, the gene expression is affected chronically as
expression variations that can persist throughout the
major alteration happens to the structure of DNA.
person's life. [119, 120].
The PEMT gene codes for a protein responsible for en-

re
dogenous choline production in the liver. An SNP in the
Genetic variation
promoter region of the PEMT gene (rs12325817) is

he
3 The expression and functionality of genes are altered due to genetic
associated with choline deficiency in humans with signif-
variations, such as single-nucleotide polymorphisms (SNPs).
icantly increased susceptibility to choline deficiency in

yw
women [119, 120].

ly

an
maintenance has become easier. Integrating the existing DFI acetyl CoA carboxylase, fatty acid synthase (FASN), and

on
database with digitized medical records can help the non- stearoyl-CoA desaturase 1 (SCD1) for lipogenesis and glu-

or
medical population be educated about their dietary re- cose 6-phosphate dehydrogenase for the pentose pathway,

e
strictions. It would be easy to access, update, and scalable. thereby promoting the accumulation of sugar as triglycer-

us

ne
Another interesting approach would be to display the DFI ides (TGs) [121-126]. Carbohydrate-responsive element-
information interactively with the existing virtual reality binding protein (ChREBP) is the key protein that governs

yo
technology. A smartphone with internet connectivity can the transcription of these genes. ChREBP forms a heterodi-
e
scan images using its camera and search the interaction of mer with Mlx (Max-like protein X, a member of the c-Myc
at

an
the scanned foods with the pre-fed drugs being medicated. family of transcription factors) and binds to fructose and
iv

In the future, it can also be integrated with wearable tech- glucose, triggering the transcription of target genes. This reg-
pr

nologies, like wearable contact lenses or glasses, most of
to
which are currently in their developmental stages. However,
security and encryption concerns, compatibility issues, and
al
ulation plays a key role in global glucose homeostasis and
sugar-induced lipogenesis. Receptor members of the family
Hepatic nuclear factor 4 (HNF-4), liver-X-receptor (LXR)

ed

lack of acceptance of the technology are a roadblock to the and FXR influence the activity of ChREBP; FXR is a key
on

development [116, 117]. transcription factor of bile acid metabolism directly interact-
ad

ing with ChREBP. LXR alpha/beta double-knockout mouse

rs

8. PERSONALIZED WELLNESS: NUTRIGENOMICS studies conclusively showed reduced ChREBP activity and
lo

AND NUTRIGENETICS
pe

lipogenic gene expression in the liver. ChREBP inhibits the

up

Nutrition research is at its golden peak, addressing and overactivation of cholesterol biosynthesis, thereby contrib-
uting to hepatoprotection in a high-fructose diet [127-129].
finding answers to the future of human health through diet
r
Fo

or

and nutrition. Each individual is unique in terms of their 8.1.2. Fat and Gene Expression
genetic makeup; genetic variation makes them respond to
Dietary fat is one of the main macronutrients that aid in
ed

different nutrients/food/diets differently. The research of

the development and growth of organisms. Besides being an
nutrigenomics and nutrigenetics considers the genome ge-
energy source, dietary fat influences gene expression, result-
ut

nomic variations and makes nutrition deeply personalized.

ing in cell differentiation and growth changes. Transcription
Nutrigenetics and nutrigenomics are the effects of the ge-
rib

factors regulated by fatty acids are identified in bacteria,

nome and genetic variations on food/nutrients intake and its
amphibians, and mammals. These factors include peroxi-
role in gene expression. High-throughout' omic' technology,
st

some proliferator-activated receptors, Hepatocyte nuclear

along with genomic information, allows us to understand the
factor 4a (HNF4a), NFkB (nuclear factor kappa B), and
di

nutrient-gene interaction and helps in developing personal-

ized nutrition [118]. SREBP1c (sterol regulatory element-binding protein 1c)
[130]. These factors are regulated by directly binding fatty
be

8.1. Nutrient Gene Interactions acids, fatty acyl-coenzyme A, or oxidized fatty acids. Eico-
sanoid regulation of G-protein-linked cell surface receptors,
ot

The nutrients in our body can interact with our genes. which activates signalling cascades, and oxidized fatty acid
Fundamentally, the nutrient-gene interactions can occur in regulation of intracellular calcium levels that affects cell
N

three ways and could potentially act as drivers of drug-food
interactions (Table 6) [119, 120].
8.1.1. Carbohydrate and Gene Expression
High intake of carbohydrates stimulates the transcription
of genes that encode the following enzymes: glucokinase
(GK) and pyruvate kinase for glycolysis, ATP citrate lyase
signalling cascades targeting the nucleus, also play a vital
role in the regulation of these factors. The physiological
reaction to fatty acids is dictated by the amount, chemistry,
and duration of the fat consumed at the cellular level. It is
also dependent on cell-specific fatty acid metabolism, the
cellular abundance of specific nuclear and membrane recep-
tors, and the involvement of specific transcription factors in
12 Recent Patents on Food, Nutrition & Agriculture, XXXX, Vol. XX, No. X Roy et al.

gene expression. Polyunsaturated fatty acid (PUFA) sup-
presses the expression of SREBP-1 and the influence of
SREBP-1 at the post-transcription level [130, 131]. PUFA
can decrease the level of mature SREBP-1 protein, presum-
ably increasing the intracellular regulatory pool of choles-
terol. In LPDS media, depriving cells of cholesterol acti-
vates enzymatic cleavage, increasing mature SREBP-1 in
the nucleus. In combination with increased mature SREBP-
1, n-3 fatty acids (FA) did not reduce the leptin mRNA lev-
el. This reveals that the PUFA-induced effect on leptin ex-
pression may involve a reduction in mature SREBP-1. Stud-
ies have shown that PUFA decreases leptin gene expression
in vivo and in vitro by reducing PPARg and SREBP-1 gene
nance and methylation of DNA synthesis of dTMP from
dUMP and efficient recycling of folate. Still, in a deficient
condition, uracil misincorporation in DNA increases chro-
mosome breaks, and DNA hypomethylation occurs [138].
Niacin is used as a substrate for poly (ADP-ribose) poly-
merase (PARP), which is involved in the cleavage and re-
joining of DNA and the maintenance of telomere length. Its
deficiency causes increased levels of unrepairable nicks in
DNA, increased chromosome breaks and rearrangements,
and sensitivity to mutagens. Vitamin A is involved in the
gene expression of PEPCK (phosphoenolpyruvate kinase),
IGF (insulin-like growth factor). Biotin is involved in vari-
ous essential protein (enzymes) syntheses at the gene level.

re
expression mechanisms [131, 132]. Vitamin C is involved in hepatic gene expression [138-140].

he
8.1.3. Protein and Gene Expression
9. CRISPR-BASED TECHNOLOGIES AND THE
FUTURE OF FOOD SCIENCE

yw
Recently, many studies have used omics technologies to
determine the impact of protein intake on metabolism. Two
"Genetic Engineering" refers to the artificial manipula-

ly
hundred eighty-one genes were differentially regulated, at

an
tion, modification, and recombination of DNA or other nu-
least two-fold in the liver of the protein-free group. Hat 11

on
cleic acid molecules in order to modify organisms or popu-
genes in cholesterol metabolism were downregulated, and
lations of organisms. CRISPR technology is an easy and

or
none of the genes in this pathway was up-regulated [133]. In
efficient method for genome editing. Clustered Regularly

e
the same study, liver transcriptomic profiles were also com- Interspaced Short Palindromic Repeats (CRISPR) and

us

ne
pared between two other diets: one made of gluten and the
CRISPR-associated sequences (Cas) are an adaptive im-
other based on casein; a lower number of differentially regu-
mune system against invasive genetic elements in bacteria.

yo
lated genes was observed (61 upregulated and 50 downregu-
e
It allows researchers to alter DNA sequences and modify
lated in the gluten group) [133]. Like the comparison be-
at
gene functions easily. Correcting genetic abnormalities,

an
tween protein-free and casein diets, cholesterol metabolism
treating and preventing the spread of diseases, and develop-
iv

was highly sensitive to the source of proteins. All 15 differ- ing crops are only a few of its many possible applications
pr

entially regulated genes in this pathway were unilaterally

to
[141, 142]. CRISPR has many practical advantages in the
increased in the gluten group compared to the casein group.
microbial industry, both natural and engineered, and could
al

Interestingly, considering the opposite expression patterns

ed

directly impact the future of food development. The

of genes involved in hepatic cholesterol metabolism, both
on

CRISPR locus allows for strain typing, a method that fin-

protein-free and gluten-free diets significantly decreased
ad

gerprints each strain, allowing for identifying proprietary

total serum cholesterol and HDL cholesterol [133-135].
rs

blends in food fermentation and probiotic products. CRISPR

lo

8.1.4. Mineral and Gene Expression naturally provides immunity against bacteriophages. How-
pe

ever, this can be harnessed to vaccinate organisms with bacte-

up

Minerals are involved in various gene expressions. Zinc,

rial viruses widely encountered in large fermentations to de-
an essential trace element and cofactor, influences many
r

crease waste in the food-manufacturing process [143]. Final-

Fo

metabolic pathways, hormone secretion pathways, and im-

or

ly, it is possible to implement CRISPR for the targeted killing

mune mechanisms [136]. One of the major components of of microbes. This may take the form of self-targeting, in
ribonucleotide reductase and mitochondrial cytochromes is
ed

which CRISPR acts as a programmable and specific antimi-

dietary iron. Iron deficiency results in decreased DNA repair
crobial agent. Self-targeting can be used as a selection marker
efficiency and increases the chances of oxidative damage to
ut

in mixed bacterial populations to screen for unique alterations

mitochondrial DNA. The level of protein HFE (hemochro-
or unusual natural mutations. An antimicrobial agent would
rib

matosis) (a newly identified mutation in a major histocom-

be used in mixed populations to remove undesirable organ-
patibility complex ( MHC) class I-like gene) is increased by isms from culture blends. Bacterial genotyping is a widely
st

increasing the status of cell iron in human intestinal cells

used application of CRISPR, especially for industrially im-
[137]. Magnesium is necessary for DNA polymerization,
di

portant lactobacilli, Streptococci, and foodborne pathogens,

nucleotide excision repair, base excision repair, and mis-
including E. coli and Salmonella. In these applications, re-
be

match repair, as well as microtubule polymerization and

searchers use the sequence variability within repeat-spacer
chromosome segregation [137].
arrays to distinguish strains. Strains can be completely identi-
8.1.5. Vitamins and Gene Expression cal in the rest of their genomes but still differences can be
ot

seen in the CRISPR systems. This allows companies to track

N

Vitamins are essential components that are needed in

both human and non-ruminant diets. Almost all vitamins
present are involved in gene expression. Vitamin C and vit-
amin E help prevent DNA oxidation and lipid oxidation. At
the same time, its deficiency is associated with increased
baseline rates of DNA strand breaks, chromosome splits,
oxidative DNA lesions, and lipid peroxide adducts on DNA.
Folate and vitamin B12 play significant roles in the mainte-
their strains specifically [144].
10. SIGNIFICANCE OF GENOMICS IN FOOD
SAFETY
Some years ago, laboratories at the FDA, USDA's food
safety and Inspection Service, and the CDC relied almost
exclusively on whole-genome sequencing (WGS) as their
Drug-food Interactions in the Era of Molecular Big Data Recent Patents on Food, Nutrition & Agriculture, XXXX, Vol. XX, No. X 13

primary surveillance tool to differentiate bacteria strains and microbial communities to provide details on a given envi-
identify related clusters of infections. Moreover, 16S meta- ronment's microbial diversity and ecology (Fig. 5) [152].
genomics techniques are used for screening the microbial The steps for metagenome sequencing and data analysis are
flora in raw materials, production environment, and finished shown in Table 7.
products. The US and many other countries use such molec-
ular-based screening of imported food [145]. Whole-
genome sequencing is the technique of determining the
complete DNA sequence of an organism's genome, which is
the organism's total genetic content. The total genetic con-
tent includes chromosomal DNA, mitochondria, and chloro-
plast (for plants). WGS is used for identifying and screening
food such as meat. More advancements in the future will
bring many food items into this list. Genetic material from

re
the species is used as markers (molecular signatures) for

he
identifying the material. Establishing these markers has be-
come easy with WGS. This can help agencies to reduce

yw
adulterations and fraudulence in food [146]. The 16S ribo-
somal RNA (rRNA) sequences that are relatively short are

ly
robust markers among all available markers for identifying

an
various species of bacteria as they are often conserved with-

on
in a species and generally different between species. The

or
advancement of next-generation sequencing, coupled with

e
the improvement in the lab protocols for capturing 16S

us

ne
rRNA, has made the process of sequencing very easy, fast,
and cheap. This technique is termed 16S-metagenomics or

yo
metagenomics and has been used to identify bacterial spe-
e
cies in any biological sample environment. Unlike the tradi-
at

an
tional methods, this technique captures the entire flora, and
iv

it can identify novel organisms and hard-to-culture species

pr

from the samples. As this technique targets the 16S rRNA, it

to
is easy to separate the microbial material from meat or vege-
al

table samples [142].

ed
on

10.1. Metagenomics for Safety Measures, Improved San-

ad

itation, and Better Shelf Life

rs

lo

As metagenomics has become very feasible in terms of Fig. (5). Overview of the process of metagenome data analysis.
pe

cost and time while offering higher accuracy, food processing

up

industries have started using it as a tool for safety auditing 11. WHOLE-GENOME SEQUENCING AND DATA
ANALYSIS
r

and quality measures. It enables them to check the microbi-

Fo

or

ome flora in their raw materials, production environment, Molecular profiling technologies are highly accessible
storage, etc. Hence, it helps modify the sanitation protocols and can be a potential tool to understand drug-food interac-
ed

based on the microbiome with newly identified food spoilage tions with better resolution. Emerging technologies that can
organisms. Screening using metagenomics allows us to un- profile genome (genomics), transcriptome (transcriptomics),
ut

derstand how microbes behave within the processing envi- microbiome (microbiomics), metabolome (metabolomics),
ronment and spoiled food. The food plant's microbiome, with
rib

epigenome (epigenomics), etc., can also be combined and

details from all plant sites, makes it easy to identify spots and analyzed in a multi-omics framework to understand the
the process that requires improvement [147, 148]. Meta-
st

molecules and potential interactions driving drug-food in-

genome and WGS are coupled together to identify and pre- teractions. In the following section, we briefly discuss the
di

vent foodborne diseases while assisting us in tracing back to concepts in genomics that are relevant to studying food-drug
the source where it originated (maybe a supply chain, produc- interactions.
be

tion line, or raw material) [149]. WGS facilitates the highly

sensitive "precision" subtyping that assists the detection, with 11.1. Short-read
higher accuracy, of foodborne disease outbreaks and aids the
ot

comprehensive characterization of foodborne pathogens and Short-read sequencing is the best platform for generating
N

identifying strains and clonal groups that differ in virulence
and antimicrobial resistance [150, 151].
10.2. Metagenome Sequencing and Data Analysis
The study of a set of genetic material (genomes) from
diverse organisms is known as metagenomics. The term
"metagenomics" is generally used to describe the study of
high-quality deep coverage for small to large size genomes.
However, short read lengths have limitations in resolving
complex regions, especially those with repetitive or hetero-
zygous sequences. Popular systems currently available pro-
duce short reads of size 50 to 150 base pairs (bp). Generated
raw data will be in fastq format, and the tranche of it is
shown in Fig. (6). It usually generates millions of short
reads for one organism of study [153].
14 Recent Patents on Food, Nutrition & Agriculture, XXXX, Vol. XX, No. X Roy et al.

Table 7. Steps for metagenome sequencing and data analysis.

Step. No. Name Details

Sequencing adapters and duplicated reads will be removed to clean up the data. Sequence chimeras are
Step 1 Data clean up an artifact of PCR amplification and subsequent next-generation sequencing. Chimeras are removed
using de novo chimera removal tools, like UCHIME of VSEARCH or a reference-based strategy.

The forward primer (V3 specific) and reverse primers (V4 specific) are trimmed, and the reads with a
quality threshold (minimum Phred score of 20) that have both pairs are identified and used for the gen-
Step 2 Consensus building
eration of V3-V4 consensus. V3-V4 consensus amplicons are built using specialized tools like FLASH
by merging these reads into an overlapping region with a certain quality length.

Total reads from all samples are pooled and clustered into OTUs based on their sequence similarity,

re
using specialized tools like Uclust, with certain similarity scores. The representative sequences from
Step 3 Picking OTU and filtering

he
each clustered OTUs are picked and aligned against curated knowledge bases, like SILVA, using tools
like PyNAST.

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Taxonomy classification can be performed using the RDP classifier by mapping each representative
Step 4 Taxonomic classification
sequence against the SILVA OTUs database.

ly

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on

or
e
us

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e
at

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pr

to
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on

ad
rs

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up
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or
ed
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rib
st
di
be

Fig. (6). Tranche of short-read sequence output. (A higher resolution / colour version of this figure is available in the electronic copy of the article).

11.2. Long-read 11.3. Linked-read

ot

Recent advancements have made a big leap from the Linked-Reads provide long-range information from
N

short-read technology and invented a few different method-
ologies to read much longer DNA fragments at the cost of a
minimal quality drop. Currently, there are a few platforms
that read DNA fragments of sizes from 10,000 bp (10 kbp)
to 60,000 bp (60 kbp). Data quality compromises are found
to be increasing proportionately with the read length [153,
154].
short-read sequencing data, which enables the capture of
information that would have been missed with other
methods. Linked-reads utilizes molecular barcodes to tag
reads from the same long DNA fragment. These unique bar-
codes added to every short read generated from an individu-
al molecule enable one to link the short reads together and
arrange them into pseudomolecules (pseudo chromosomes).
Drug-food Interactions in the Era of Molecular Big Data Recent Patents on Food, Nutrition & Agriculture, XXXX, Vol. XX, No. X 15

Chromosome conformation capture (3C/Hi-C/Capture-C)
method is used to study the 3-D architecture of genomes,
which helps unveil the 3-D folding of chromosomes and the
arrangement of distant functional elements, such as promot-
ers and enhancers, and hence reveals the relationship be-
tween chromosome organization and genome activity. Hi-C
methodology produces high-quality short-read data that help
arrange the assembled contigs/scaffolds for building chro-
mosome-level assemblies [155].
11.4. Optical Mapping
Optical mapping platforms use optical maps generated
the individual (variant calling analysis mentioned below)
while the target would be to build a genome assembly (de
novo analysis discussed below) if the genome is not availa-
ble.
11.5. De novo Assembly and Annotation and Genome
Assembly
Genome assembly stitches millions of DNA fragments
together to form the DNA sequences. All sequencing proto-
cols (short and long read) generate multiple copies of over-
lapping fragments. The assembly algorithms search for the
overlapping pieces and stitch them to build bigger pieces as

re
by fluorescent-labelled ultralong DNA molecules of >150 long as possible. The overall process of genome assembly
kb in length. A de novo optical map assembly can be com- building is illustrated in Fig. (7). [158] Genome assembly is

he
pared to a DNA sequence assembly. It can be used to correct a computationally challenging task that requires a high
wrong assemblies, stitch scaffolds, and correct incorrect amount of memory (RAM) and storage (hard disk space).

yw
assembly of contigs sequences in highly complex areas of Computational and time requirement is exponentially pro-
the genome. This platform's next-generation mapping com- portional to the genome size and input data size. Many dif-

ly

an
bines proprietary Nano-channel arrays with optical mapping ferent algorithms are available in the open-source domain

on
to image extremely long, high-molecular-weight DNA in its for building assemblies from various data types. Many of
most native state. Optical mapping also enables structural them are hybrid assemblers capable of using different data

or
variation detection with high sensitivity and obtains highly types together and building the assembly. Extensive re-

e
contiguous genome assemblies [156, 157]. The data gener- search is focused on this, and better strategies are coming

us

ne
ated can be analyzed mainly in two different strategies out every year [159, 160]. Popular assembly tools are listed
based on the availability of the reference genome. In that in Table 8.

yo
e
case, the study will focus on the variations in the genome of
at

an
iv

Table 8. Popular assembly tools.

pr

to
Assembly Tool References Type of Input Data
al

ed
on

Zerbino, D. R., & Birney, E. (2008). Velvet: Algorithms for de novo short read assembly using de Bruijn Illumina PE, Illumina
ad

Velvet graph. Genome Research, 18(5), 821-829. https://doi.org/10.1101/gr.074492.107 MP

rs

lo

Simpson, J. T., Wong, K., Jackman, S. D., Schein, J. E., Jones, S. J. M., & Birol, I. (2009). ABySS: A parallel
Illumina PE, Illumina
pe

assembler for short-read sequence data. Genome Research, 19(6), 1117-1123.

up

MP
ABySS https://doi.org/10.1101/gr.089532.108
r
Fo

Anton Bankevich, Sergey Nurk, Dmitry Antipov, Alexey A. Gurevich, Mikhail Dvorkin, Alexander S. Kuli-
or

kov, Valery M. Lesin, Sergey I. Nikolenko, Son Pham, Andrey D. Prjibelski, Alexey V. Pyshkin, Alexander V.
Illumina PE, Illumina
Sirotkin, Nikolay Vyahhi, Glenn Tesler, Max A. Alekseyev, and Pavel A. Pevzner. SPAdes: A New Genome
ed

MP, PacBio, Nanopore

Assembly Algorithm and Its Applications to Single-Cell Sequencing. Journal of Computational Biology 19(5)
SPAdes (2012), 455-477
ut
rib

Wick, R. R., Judd, L. M., Gorrie, C. L., & Holt, K. E. (2017). Unicycler: Resolving bacterial genome assem-
Illumina PE, Nanopore,
blies from short and long sequencing reads. PLoS Computational Biology, 13(6), 1-22.
PacBio
st

Unicycler https://doi.org/10.1371/journal.pcbi.1005595
di

1. Luo, R., Liu, B., Xie, Y., Li, Z., Huang, W., Yuan, J. & Wang, J. (2012). SOAPdenovo2: an empirically Illumina PE, Illumina
SOAPdenovo2 improved memory-efficient short-read de novo assembler. Gigascience, 1(1), 18. MP
be

Zimin, A. V., Marçais, G., Puiu, D., Roberts, M., Salzberg, S. L., & Yorke, J. A. (2013). The MaSuRCA ge- Illumina PE, Illumina
MaSuRCA nome assembler. Bioinformatics, 29(21), 2669-2677 MP, PacBio, Nanopore
ot
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1. Pryszcz, L. P., & Gabaldón, T. (2016). Redundans: An assembly pipeline for highly heterozygous genomes. Illumina PE, Illumina
Redundans Nucleic Acids Research, 44(12), e113. https://doi.org/10.1093/nar/gkw294 MP

Lin, Y., Yuan, J., Kolmogorov, M., Shen, M. W., Chaisson, M., & Pevzner, P. A. (2016). Assembly of long
PacBio, Oxford Na-
error-prone reads using de Bruijn graph. https://doi.org/10.1073/pnas.1604560113/-
nopore
flye /DCSupplemental.www.pnas.org/cgi/doi/10.1073/pnas.1604560113
(Table 8) Contd…
16 Recent Patents on Food, Nutrition & Agriculture, XXXX, Vol. XX, No. X Roy et al.

Assembly Tool References Type of Input Data

Koren, S., Walenz, B. P., Berlin, K., Miller, J. R., Bergman, N. H., & Phillippy, A. M. (2017). Canu : scalable
PacBio, Oxford Na-
canu and accurate long-read assembly via adaptive k -mer weighting and repeat separation. 722-736.
nopore
https://doi.org/10.1101/gr.215087.116.Freely

Kajitani, R., Toshimoto, K., Noguchi, H., Toyoda, A., Ogura, Y., Okuno, M., … Itoh, T. (2014). Efficient de
Illumina PE, Illumina
Platanus novo assembly of highly heterozygous genomes from whole-genome shotgun short reads. 1384-1395.
MP
https://doi.org/10.1101/gr.170720.113.Freely

Gnerre, S., Maccallum, I., Przybylski, D., Ribeiro, F. J., Burton, J. N., Walker, B. J., … Jaffe, D. B. (2011).
Illumina PE, Illumina
ALLPATHS-LG High-quality draft assemblies of mammalian genomes from massively parallel sequence data. 108(4), 1513-
MP, PacBio
1518. https://doi.org/10.1073/pnas.1017351108

re
Kronenberg, Zev & Hall, Richard & Hiendleder, Stefan & Smith, Tim & Sullivan, Shawn & Williams, John &

he
FALCON Kingan, Sarah. (2018). FALCON-Phase: Integrating PacBio and Hi-C data for phased diploid genomes. PacBio long reads
10.1101/327064.

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Hailin Liu,Shigang Wu,Alun Li,Jue Ruan,SMARTdenovo: a de novo assembler using long noisy

ly

an
SMARTdenovo reads,Gigabyte,1,2021 PacBio, Nanopore

on
https://doi.org/10.46471/gigabyte.15

or
Li, H. (2016). Sequence analysis Minimap and miniasm : fast mapping and de novo assembly for noisy long

e
Miniasm sequences. 32(March), 2103-2110. PacBio, Nanopore

us

ne
https://doi.org/10.1093/bioinformatics/btw152

yo
Qin, M., Wu, S., Li, A., Zhao, F., Feng, H., Ding, L., & Ruan, J. (2019). LRScaf : improving draft genomes
e
LRscarf PacBio, Nanopore
using long noisy reads. 1-12.
at

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Fig. (7). Overview of the process of the genome assembly building.

Drug-food Interactions in the Era of Molecular Big Data Recent Patents on Food, Nutrition & Agriculture, XXXX, Vol. XX, No. X 17

re
he
yw
ly

an
on

or
Fig. (8). Process of genome annotation in detail.

e
us

ne
11.6. Repeat Discovery 12. EMERGING TRENDS IN DRUG-FOOD
INTERACTIONS AND OUTLOOK

yo
Almost all eukaryotic and few prokaryotic genomes con-
e
at
tain different repeat elements associated with many structur- Drug-nutrition interaction at present is an area that is

an
al (e.g., chromosomal organization) and functional (e.g., highly underrated and overlooked. Adult multimorbidity is
iv

gene regulation) activities. There are established strategies increasing rapidly, contributing to polypharmacy and raising
pr

to discover repeat regions and repeats that use models with the likelihood of significant drug-drug interactions. Vita-
to
priori knowledge. RepeatMasker is one such tool. This mins as essential nutrients have central metabolism func-
al

strategy fails to identify novel repeats, and some species tions; therefore, interactions and insufficient availability of
ed

have large numbers of novel repeats. A couple of computa- vitamins can lead to critical metabolism impairments. The
on

tional tools (e.g., RepeatModeler) are currently proven to effect of a patient's diet or dietary supplements on medica-
ad

perform the task of novel repeat identification [161,162]. tion and drug effectiveness is an emerging area. Especially
rs

in the field of oncology, there is a growing trend towards

lo
pe

11.7. Gene Discovery oral delivery of anticancer drugs and self-medication with
up

Genes are functional elements of genomes. Identifying nutritional supplements; thus, the knowledge of the kinetics
and chemistry of the activation of anticancer bio-reductive
r

the gene components in the genome is termed gene discov-

Fo

or

medicines, identifying the metabolic enzymes involved in

ery. The task is to determine the coordinates of such com-
the bioactivation, and data of their nutritional regulation will
ponents in the assembled genome. Ab initio strategies are
help in managing cytotoxicity.
ed

utilized heavily in this process, where the mathematical

models built using the priori knowledge are utilized as sup- Developing new functional foods to optimize the inter-
ut

porting data. Some of these algorithms allow us to use cus- action between current foods and current drugs and identify
tom-made models too. Some tools accept protein sequences, novel functionalities of both old and new food ingredients
rib

RNA sequences, and sequences of expressed sequence tags while addressing multiple aspects of the patient's nutritional
(EST) and use them as evidence to score the ab initio pre- challenges are emerging areas filled with potential and
st

dictions [163, 164]. promise. A better understanding of drug-food interactions

di

11.7.1. Function Annotation of Genes offers the possibility of setting specific dietary guidelines
and recommending special diets, suitable foods, or supple-
be

Identifying the functions of the genes discovered are ments to patients, thereby increasing the effectiveness of the
called function annotation. The most popular strategy for treatment.
ot

this task is to sequence similarity-based search (homology

search) in various sequence databases like NCBI and Uni- 13. CURRENT AND FUTURE DEVELOPMENTS
N

Prot. Multiple blast algorithms are used in this process. Dietary risks impact people of all ages, genders, and
Computational tools like “Prediction of Unassigned Re-
sociodemographic backgrounds. Food can be used to avoid
gions: PURE; available via https://caps.ncbs.res.in/PURE,
chronic diseases and metabolic syndromes, like obesity,
can be used to assign functions to novel protein regions.
diabetes, hypertension, dyslipidemia, and drug-nutrient in-
Researchers around the globe use highly customized strate-
teractions could alter the pharmacokinetics and pharmaco-
gies that utilize knowledge related to protein domains, pro-
dynamics of drugs. Pharmacokinetics is the quantitative
tein family, ortholog clusters, etc. (Fig. 8) [165-169]. elucidation of drug disposition that consists of absorption,
18 Recent Patents on Food, Nutrition & Agriculture, XXXX, Vol. XX, No. X Roy et al.

metabolism, distribution, and excretion, whereas pharmaco- sion of the manuscript. LS KY, and KS contributed to the
dynamics is the clinical effect of the drug, which can be overall planning of the manuscript. All authors read and
manifested either by a reduction in bioavailability or an increase approved the final manuscript.
in bioavailability that can result in toxicities [55, 57, 76].
LIST OF ABBREVIATIONS
The ability of food to interfere with drug treatment is a
major concern in clinical practice. Knowledge of drug-food ARE = Antioxidant Response Element
interactions is helping us identify, predict, and prevent un-
IBD = Inflammatory Bowel Disease
wanted interactions between food and marketed or novel
drugs. To interpret the biological responses to diet, as well INR = International Normalized Ratio
as to assign the importance of drug-food interaction, all RNA = Ribonucleic Acid
available information on the chemical background of the
small molecules in our diet is assembled on interaction net- EST = Expressed Sequence Tags

re
works [71, 74].
CONSENT FOR PUBLICATION
Nutrigenetics and nutrigenomics help to map the ge-

he
nome's effects and genetic variations on food/nutrients in- Not applicable.
take and its role in gene expression. High-throughput omics

yw
technologies and genomic information allow us to under- FUNDING

ly
stand the nutrient-gene interaction and help develop person-

an
None.
alized nutrition [118, 170, 171]. Whole-genome sequenc-

on
ing helps determine the complete DNA sequence of an CONFLICT OF INTERESTS

or
organism’s total genetic content or its genome. Nutri-
KS received salary, consulting fees or honoraria from

e
genetics and nutrigenomics are becoming ever more evident
Philips Healthcare, Kencor Health, OccamzRazor, Alphabet,

us

ne
and play a central role in analysing dietary impacts on health
outcomes and the systematic assessment of nutrient impacts McKinsey& Company, BCG, LEK. KS has been an em-
ployee of AstraZeneca at the time of publication. LS re-

yo
by a multitude of 'omic' technology biomarkers. Some of
e
these technologies are still in their infancy, while others are ports being a cofounder of Entrupy Inc, Velai Inc and Gaius
at
Networks Inc, and has served as a consultant for the World

an
much more mature [145, 172]. As metagenomics has be-
iv

come very feasible in terms of cost and time while offering Bank and the Governance Lab.
pr

higher accuracy, food processing industries have started

to
using it as a tool for safety auditing and quality measures. It ACKNOWLEDGEMENTS
enables them to check the microbiome flora in their raw
al

Declared none.
ed

materials, production environment, storage, etc. Hence, it

on

helps modify the sanitation protocols based on the microbi- REFERENCES

ad

ome with newly identified food spoilage organisms. Meta-

rs

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