CHILDHOOD OBESITY

Month 2022 j Volume X, Number X

ORIGINAL ARTICLE
ª Mary Ann Liebert, Inc.
DOI: 10.1089/chi.2022.0059

Open camera or QR reader and

scan code to access this article
and other resources online.

Probiotic Use in Children and Adolescents

with Overweight or Obesity: A Scoping Review
Michelle H. Loy, MD,1–3 John Usseglio, MPH,4
Danielle Lasalandra, DO,5 and Melanie A. Gold, DO, DMQ6–8
Downloaded by Morocco Hinari Band 2 from www.liebertpub.com at 11/08/22. For personal use only.

Abstract
Context: Probiotics have been proposed as a prevention or treatment for pediatric overweight and obesity.
Objective: Conduct a scoping review on probiotic use in children and adolescents with overweight or obesity and those with
weight-related conditions and to identify knowledge gaps and research priorities.
Data Sources: Seven databases using keywords and medical subject heading terms for articles reporting probiotic use in children
or adolescents with overweight or obesity published from database conception until initiation of the study.
Study Selection: Articles reporting primary data on probiotics use in children or adolescents with overweight or obesity.
Data Extraction: We utilized the Arksey and O’Malley framework, PRISMA (Preferred Reporting Items for Systematic Reviews
and Meta-Analysis) guidelines, followed a predetermined study protocol for level-one abstract and level-two full-text screenings,
synthesized information into subject-area domains, and identified research gaps.
Limitations: Heterogeneity of probiotic interventions, host factors, and genomics.
Results: Database search yielded 1356 unique articles with 19 randomized placebo-controlled studies, 945 participants, duration of
interventions from 8 weeks to 9 months. Disease indications included Nonalcoholic Fatty Liver Disease, insulin resistance, hy-
percholesterolemia, Prader–Willi Syndrome, metabolic syndrome, and obesity. Limited and heterogeneous evidence for probiotic
use in children and adolescents with weight-related conditions noted. Heterogeneity among published articles in probiotic strains,
doses, design, biomarkers, confirmation, and outcomes observed.
Conclusions: Despite complex existing and limited data, studies to date of children and adolescents with overweight and obesity
demonstrate potential beneficial treatment effects of probiotics on BMI, adiposity, metabolic parameters, inflammatory markers,
fatty liver, transaminase levels, and glucose metabolism. Clinical trials to address heterogeneous results are needed.

Keywords: adolescent; child; clinical trials; microbiota; obesity; overweight; pediatric; prebiotic; probiotics; review; weight reduction

Introduction is a global epidemic.1 Due to the lack of effective pre-

vention and treatment interventions, using probiotics to
ith over 340 million children and adolescents prevent and manage conditions, including diabetes and

W 5–19 years of age classified as overweight or

obese in 2016, pediatric and adolescent obesity
obesity has been proposed.2 Probiotics are microorganisms
promoted with claims of health benefits when consumed.

Departments of 1Pediatrics and 2Medicine, Weill Cornell Medicine, New York, New York, USA.
3
Integrative Health and Well-Being, Weill Cornell Medicine/New York Presbyterian Hospital, New York, New York, USA.
4
Health Sciences Library, Columbia University Irving Medical Center, New York, New York, USA.
5
Stamford Hospital, Stamford, Connecticut, USA.
6
Heilbrunn Department of Population and Family Health, Columbia University Mailman School of Public Health, New York, New York, USA.
7
Section of Adolescent Medicine, Division of Child and Adolescent Health, Department of Pediatrics, Columbia University Irving Medical Center,
New York, New York, USA.
8
Center for Community Health and Education, School-Based Health Centers, NewYork Presbyterian, New York, New York, USA.

1
 2 LOY ET AL.
Prebiotics are nondigestible food ingredients that induce
the growth or activity of beneficial microorganisms such as
bacteria or fungi. Synbiotics are mixtures of probiotics and
prebiotics that benefit the host.
Although no specific composition of an obesogenic
gut microbiota profile has been determined, comparative
research indicates that gut microbiota of children with
obesity is distinct from normal weight children.3 Given
different compositional development of gut microbiota
in adults and children with overweight, interest has grown
in examining possibilities for preventative and thera-
peutic applications of specific probiotic strains in weight
management.
However, controversial data highlight that the connec-
tion between microbiota composition and excess weight is
very complex.4 For example, data show positive correla-
Downloaded by Morocco Hinari Band 2 from www.liebertpub.com at 11/08/22. For personal use only.
tion between Lactobacillus reuteri and obesity, whereas
Bifidobacterium animalis has been associated with a lower
BMI.
Several mechanisms have been proposed regarding pro-
biotics, obesity, and downstream clinical effects. Murine
model studies have suggested that some strains of Bifido-
bacterium and Lactobacilli have an effect on obese status
by reducing serum total cholesterol, decreasing proin-
flammatory cytokines, and increasing glucose tolerance.5–8
However, researchers concluded that in vivo administra-
tion of probiotics in children or adults with obesity needs to
be further investigated.4 Explanations for how gut micro-
organisms impact the development of obesity include an
improvement of the energy harvest from diet, influence on
lipase activity, a decrease of lipopolysaccharide inflam-
mation, control of endotoxemia, and insulin resistance.9 It
should also be noted that without clear data of intestinal
colonization, it is an assumption that consumed probiotics
relate directly to fecal bacteria.
Bifidobacterium have been shown to be higher in
number among children who remained normal weight at
7 years10 compared with children who became overweight
and have been found to be associated with lean status.11
In contrast, Lactobacillus subspecies, Staphylococcus
aureus, and Escherichia coli have been associated with
overweight status. Furthermore, other studies reported a
decrease of total Bifidobacterium in the feces of patients
with obesity.12,13 A positive correlation was found between
certain Lactobacillus species, in particular Lactobacillus
reuteri and adult obesity, whereas B. animalis has been
associated with a lower BMI in adults.14
There are fewer reported studies of probiotic use for
pediatric and adolescent obesity compared with probiotic
use in adult obesity. In addition, most of the literature
surrounding probiotic use in pediatric obesity is limited to
Nonalcoholic Fatty Liver Disease (NAFLD). The gap in
the literature we seek to explore is which (if any) probiotic
species, specific strains, and combinations of strains have
evidence for preventing and managing childhood and ado-
lescent obesity, not restricted to NAFLD diagnosis.3 To
our knowledge, there has not been a scoping review or
systematic review published on the association of probiotic
use in reducing weight in children and adolescents with
overweight or obesity or those with weight-related condi-
tions other than NAFLD.
Methods
To examine the literature on probiotic use for weight
reduction in overweight and obese children and adoles-
cents, we conducted a scoping review to assess the degree
of heterogeneity in probiotic trial design, strains tested,
proof of colonization, outcomes tested, and evidence for
use of probiotics in children and adolescents with over-
weight, obesity, or weight-related conditions reported.
Given the state of the current literature and the lack of
knowledge on the subject, we aimed to cast a broad net.
We included studies with a range of primary outcomes as
we did not want to limit the scoping review by limiting the
studies under consideration. Our goal was to be inclusive
of all the literature on probiotics, children, and weight.
A scoping review is an appropriate study design for
research questions that are open-ended in a subject area
with a limited existing body of research.14 A scoping
review is a type of literature review that includes a wide
range of study designs, including gray literature, to identify
important subject area domains, existing evidence, and
gaps in knowledge.14 Gray literature, evidence not pub-
lished in commercial publications, can include academic
articles, including theses and dissertations, research and
committee reports, government reports, conference papers,
and ongoing research, among others. It comprises publi-
cations that fall outside of traditional commercial and
academic publishing and distribution channels. The goal of
a scoping review is to ‘‘map the body of literature on a
topic area.’’15 This scoping review aims to identify and
critically assess the existing data on probiotic use in chil-
dren and adolescents with overweight or obesity, synthe-
size the existing data into key subject area domains, and
identify knowledge gaps in the current body of literature
and future research priorities.16
We utilized the Arksey and O’Malley framework with
Levac and colleagues enhancements to guide our scoping
review methodology.14,17 We also followed the Preferred
Reporting Items for Systematic Reviews and Meta Ana-
lyses for Scoping Reviews (PRISMA-Scr) guidelines to
conduct the review.18 After identifying the research ques-
tion, one author (M.L.) met with a health sciences research
Informationist ( J.U.) who assisted with defining search
terms and provided recommendations on appropriate data-
bases to search for the review. We selected databases that
included both peer-reviewed and gray literature (SCOPUS,
clinicaltrials.gov). The search terms were developed in
an iterative process to develop comprehensive strategies.
While we planned an iterative process, we trialed a few
articles looking at a priori domains but no new domains
were identified. On February 27th, 2020, searches were
conducted in PubMed, Ovid Medline, Cochrane Library,
 CHILDHOOD OBESITY MONTH 2022
Embase, Cumulative Index of Nursing and Allied Health
Literature (CINAHL), SCOPUS, and the Web of Science.
The search was updated on March 4th, 2021.
Search terms were grouped into four concepts that were
combined with the Boolean AND operator: adolescent/
child/infant, obesity and obesity-related diseases, probiotic
intervention, and disease outcomes of interest. For full
records of the search strategies utilized in this review,
please see the first Appendix A1. Our PRISMA flow dia-
gram can be found in Figure 1.
We created a study protocol agreed upon by the authors,
with inclusion and exclusion criteria for the abstract and
full-text screening process. Our inclusion criteria were:
(1) Randomized controlled, double blinded, placebo con-
trolled (2) infant/pediatric/adolescent (3) strain/genus/
dose/probiotic colony-forming unit (4) overweight/
Downloaded by Morocco Hinari Band 2 from www.liebertpub.com at 11/08/22. For personal use only.
obesity/obesity-related disorders (5) hypertension, type 2
diabetes, NAFLD, obstructive sleep apnea (OSA), dysli-
pidemia (6) confirmation testing (7) English language,
(8) any year of publication, and (9) Full-text journal arti-
cles included in the database. We excluded reviews, letters,
case reports or series, abstracts, and editorials. There were
no restrictions on sex, race or ethnicity, number of partic-
ipants, or year of publication. The exclusion criteria were
articles not written in English, adult or pregnant popu-
lations, animal studies, noninterventional trials (review
Figure 1. PRISMA-ScR.
3
article, systematic review), trials without probiotics (pre-
biotics only or diet), and those with no mention of obe-
sity or obesity-related disease. For level one screening,
two authors (M.L., D.L.) separately reviewed the 1356
abstracts identified. They voted to exclude or include each
abstract according to the preset criteria.
There was moderate (Cohen’s Kappa = 0.60) level of
agreement between the reviewers.19 A third author (M.G.)
determined whether to include the abstract when there was a
disagreement. For level-two screening, two authors (M.L.,
D.L.) conducted the full-text review and chose to include
or exclude based on the preset criteria. There was strong
(Cohen’s Kappa = 0.84) level of agreement between the re-
viewers.19 A third author (M.G.) decided whether to include
or exclude when there was a disagreement. The modest
kappa coefficient at the abstract level is likely due to the
heterogeneity in the number of articles and types of re-
search. There was stronger agreement for the full-text stage.
We performed the data extraction as an iterative process.
One member of the research team (M.L.) first extracted
basic data and results from each article. The first round of
extracted data included: Study ID, reviewer name, title of
article, lead author contact details, country in which study
conducted, aim of study, study design, start/end date,
study funding sources, possible conflicts of interest for
study, population description, inclusion/exclusion criteria,
 4 LOY ET AL.
total number of participants, intervention, comparison group,
outcome, how outcome was ascertained, whether stool was
analyzed, how was stool analyzed (16S/Shotgun), specific
dosing and strain of probiotic, and conclusions. The 16S
rRNA gene sequencing, or simply 16S sequencing, utilizes
PCR to target and amplify portions of the hypervariable
regions (V1–V9) of the bacterial 16S rRNA gene. Shotgun
sequencing is a laboratory technique for determining
the DNA sequence of an organism’s genome. The articles
were appraised for key topic domains and study limitations
were identified.
We met monthly to discuss findings and refine data
extraction methods. We then created a list of key subject
area domains. Experts in pediatric and adolescent medi-
cine, pediatric obesity, and a PhD RD who conducts
research related to probiotics reviewed the list of domains
Downloaded by Morocco Hinari Band 2 from www.liebertpub.com at 11/08/22. For personal use only.
and provided input. We compiled a list of the key domains
identified by the authors and subject area experts. One
author (M.L.) reviewed the final sample of articles again
and extracted information about each domain. The authors
then compiled and synthesized the information and iden-
tified gaps in knowledge within the key domains.
Selection of Active or Ongoing Registered
Clinical Trials
Clinical trial registries were searched, including Clin-
icalTrials.gov and WHO ICTRP. The inclusion and
exclusion criteria were as described previously, in addition
to trial status as active, recruiting, not completed, or not
reported.
Results
Out of 2003 identified studies, 19 studies met the eligibility
criteria (Fig. 1). After thorough review, final analysis inclu-
ded 19 placebo-controlled trials comprising 945 participants,
ages 4 months to 19 years. Duration of intervention ranged
from 8 weeks to 9 months. Disease indications included
NAFLD, insulin resistance, hypercholesterolemia, Prader–
Willi Syndrome, metabolic syndrome, overweight, and obe-
sity. Countries of investigation included China, Denmark,
Finland, Iran, Italy, Spain, and USA (Table 1).
All studies evaluated the use of probiotics in obesity and
obesity-related conditions. Some probiotic interventions
included additional synbiotic preparations, dietary, or
physical activity prescriptions. Anthropometric markers,
metabolic markers, inflammatory markers, hepatic chan-
ges, microbiome changes, and other changes were assessed
by blood, stool, imaging, DEXA, MRI, urinary metabolic
profiling, dietary, and psychological questionnaires. Trial
designs were heterogeneous in the type of probiotic
interventions and outcome measures. Only 16% of the
trials had 16S PCR testing to confirm colonization. There
was heterogeneity in trial primary endpoints. Primary
outcomes included improvements in BMI, liver enzymes,
lipid markers, insulin and glucose metabolism, inflamma-
tory markers, and adiposity (Table 2).
Overall, of the 19 studies included, only one of the 19
addressed obesity prevention, the others investigated obe-
sity treatment. Of the 19 studies included, 16 studies
showed benefits for probiotic supplementation as it relates
to obesity or weight-related conditions. Two other stud-
ies (one of which was the prevention study) showed no
effect,20,21 and one showed a negative effect22.
As seen in Table 1, 12 of the 19 studies included pro-
biotics in combination with other treatment modalities
(diet, exercise, prebiotics), whereas seven looked at pro-
biotics alone.
Types of Probiotics
A range of probiotics was investigated, including
Lactobacillus acidophilus, Lactobacillus paracasai, Lac-
tobacillus casei, Lactobacillus salivarius, Lactobacillus
rhamnosus, Lactobacillus bulgaricus, Lactobacillus del-
brueckii, Streptococcus thermophilus, B. animalis, Bifido-
bacterium lactis, Bifidobacterium breve, Bifidobacterium
longum, and Bifidobacterium pseudocatenulatum. The dos-
ing, combination of species and strains, as well as the
use in combination of prebiotic/probiotic treatment was
heterogeneous.
Obesity Prevention
Of the-19 studies included, only one study assessed
obesity prevention,20 in which healthy newborns given
probiotics at ages 4–13 months had follow-up body com-
position studies at ages 8–9 years. Lactobacillus paracasei
F19 (10 · 8 CFU) had no effect on body composition,
metabolic markers, and inflammatory markers at school-
age follow-up.
Obesity Treatment–Positive Effects
Regarding the treatment of obesity, six studies showed
an association between probiotic use and reduction in
BMI,23–28 with beneficial secondary outcomes in inflam-
matory markers, lipid markers, glucose metabolism, and
hepatic measures. Seven studies29–35 did not show BMI
improvement with probiotic use but did show improve-
ments in inflammatory markers, adiposity, waist circum-
ference, fasting insulin, HOMA-IR, ultrasound results,
liver function tests, cholesterol, triglycerides, behavioral
and mental health, and social withdrawal.
Among the six studies showing BMI improvement, the
species and doses differed. Three of the six studies used
VSL#3. VSL#3 is a high-concentration probiotic prepa-
ration of eight live freeze-dried bacterial species, including
four strains of lactobacilli (L. casei, Lactobacillus plan-
tarum, L. acidophilus, and Lactobacillus delbrueckii
subsp.), three strains of Bifidobacterium (B. breve, B.
longum, and Bifidobacterium infantis, and one strain of
Streptococcus (Streptococcus salivarius subspecies ther-
mophilus). The studies used different dosing (1–2 sachet
per day depending on age), and various strains/combina-
tions, including B. longum, L. bulgaricus, S. thermophilus
combination (no CFU reported), B. pseudocatenulatum
 Downloaded by Morocco Hinari Band 2 from www.liebertpub.com at 11/08/22. For personal use only.

Table 1. PICO Summary

Stool analysis -
Study Study Comparison Dose/strain 16S/shotgun/
Study design length Population Size Intervention group Outcome of probiotic unknown
Alisi et al. RCT 4 months Pediatric, BMI >85%, 44 VSL #3 +low cal. Placebo + low cal. VSL#3 significantly VSL#3
(2014) NAFLD diet + aerobic diet + aerobic improves NAFLD;
exercise exercise VSL#3 increases
GLP-1 and decreases
BMI. No between-
group differences in
TG, HOMA, ALT.
Amat-Bou RCT 12 weeks PWS, ages 2–19 39 100 mg of Bifido 300 mg of No effects on 100 mg of QIAamp
et al. animalis lactis maltodextrin microbiota, fat mass, Bifidobacterium animalis PowerFecal
(2020) hyperphagia, bp, lipid subsp.lactis (BPL1, DNA Kit to
profile, glucose, and CECT8145, 1010 CFU) sequence
HgA1C. BPL1 region V3–V4
decreased fasting of bacterial
insulin, HOMA-IR, 16S gene
abd. fat, mental
health symptoms.
Chen et al. RCT 12 weeks 6–14 years; obese 54 Probiotic + Placebo + reduced Improved BMI, IL-6, No CFU, B. longum,
(2019) reduced calorie calorie intake + LPS,TNF alpha, TG, L. bulgaricus,

5
intake + increased increased physical fasting BG, insulin, S. thermophilus
physical activity activity and HOMA-IR
Famouri RCT 12 weeks 10–18 years, BMI 64 Probiotic capsule Placebo Probiotic decreased 1 capsule Prokid:
et al. >85%, NAFLD (Lactobacillus/ AST, ALT, L. acidophilus ATCC
(2017) Bifidobacterium) cholesterol, B3208, 3 · 109 CFU;
lipoprotein-C, TG, B. lactis DSMZ32269,
and abnormal U/S. 6 · 109 CFU; B. bifidum
No change in weight ATCC SD6576,
& BMI. 2 · 109 CFU; L.
rhamnosus DSMZ
21690, 2 · 109 CFU.
Gøbel et al. RCT 12 weeks Ages 12–15, obesity 50 Ls-33 Placebo No differences in L. salivarius Ls-33 Quant. PCR,
(2012) anthropometrics, ATCC SD5208 16S, L.
lipids, glucose/ 1010 CFU salivarius
insulin, inflammatory detected in
markers, fecal 24/27 subjects
calprotectin. in probiotic
after intake
Gombert Treatment/ 13 weeks Obese children; insulin 48 Probiotic + dietary Placebo + dietary Improved BMI, CRP, B. pseudocatenulatum Unknown
et al. (2019) Control resistance recommendations recommendations HDL, and increased CECT 7765, 10 CFU
Groups Rikenellaceae
continued on page 6
 Downloaded by Morocco Hinari Band 2 from www.liebertpub.com at 11/08/22. For personal use only.

Table 1. PICO Summary continued

Stool analysis -
Study Study Comparison Dose/strain 16S/shotgun/
Study design length Population Size Intervention group Outcome of probiotic unknown
Goyal et al. RCT 4 months Ages 5–18, obesity 106 VSL#3 +lifestyle Placebo VSL#3 + lifestyle VSL #3 - 112.5 billion
(2019) NAFLD (diet and physical significantly reduced (B. breve, B. infantis,
activity), VSL, fatty liver grades, B. longum,
lifestyle only anthropometric, L. acidophilus,
biochemical L. planetarium,
parameters, obesity L. paracasei,
hormones compared L. delbrucki subspecies
with VSL#3 alone, bulgaricans), and
and lifestyle S. thermophilus
intervention alone.
Herrera RCT 12 weeks 7–16 years; BMI >85% 39 Probiotic + high- Placebo + high- Decrease in CRP and VSL #3
et al. (2018) fruit/vegetable diet fruit/vegetable diet TNFa
Jones et al. RCT 16 weeks 12–18 years; BMI >95; 19 Probiotic with Placebo with Increased total/trunk VSL #3, 3 packets, 16S rRNA
(2018) Hispanic VitaminWater VitaminWater adiposity with no Combo of
Zero (erythritol + Zero (erythritol + significant effects on Streptococcus
stevia) stevia) liver fat/fibrosis, Bifidobacterium, and
insulin/glucose, gut Lactobacillus strains
microbiome/
hormones
Kelishadi RCT 8 weeks 6–18 years; BMI 85%+ 56 Probiotic, Placebo + lifestyle Decreased TNFa and One Protexin capsule Colony

6
(2014) prebiotic, vitamins mod counseling IL-6 of 2.0 · 108 (CFU)/day counting
qD + lifestyle mod Combo of: performed by
counseling Lactobacillus, expert
Streptococcus,
Bifidobacterium
strains with prebiotic
(FOS), vitamin A/C/E.
Kianifar RCT 12 weeks Ages 7–13, BMI above 46 Diet/physical Diet/physical Reductions in waist Protexin Synbiotic:
et al. (2018) 85% or 95% activity+ synbiotic activity + placebo circ. only in synbiotic 100 million CFU
capsule group; BMI combination (L. casei,
decreased in both L. rhamnosus,
groups. S. thermophilus,
B. breve, L. acidophilus,
B. infantis, L. bulgaricus)
+ prebiotic and
vitamins
Larsen RCT 12 weeks 12–15 years; BMI >30 51 Probiotic Placebo Increase in L. salivarius Ls-33 16S rRNA
et al. (2013) Bacteroides- ATCC SD5208
Prevotellae: (1010 CFU per
Firmicutes ratio capsule)
Mandato and DBPC 8 weeks 9–13 years; obese w/ 20 Probiotic Placebo Decreased ALT 12 billion CFU, L.
colleagues pilot hypertransaminasemia rhamnosus strain GG
(2011) and bright liver
continued on page 7
 Downloaded by Morocco Hinari Band 2 from www.liebertpub.com at 11/08/22. For personal use only.

Table 1. PICO Summary continued

Stool analysis -
Study Study Comparison Dose/strain 16S/shotgun/
Study design length Population Size Intervention group Outcome of probiotic unknown
Miccheli RCT 4 months Children; BMI >85% 31 Probiotic + VLC Placebo + low-cal. Improved BMI, fatty 1 sachet per day of
et al. (2015) with NAFLD diet and aerobic diet and moderate liver, AST, and VSL if <10, 2 sachet
exercise aerobic exercise GLP-1 if >10
Passariello PRCC 6 months 6–12 years; familial 40 Synbiotic + low-sat Low-sat fat diet Improved LDL, TC, 2.5 · 109 CFU BID,
(2016) hypercholesterolemia fat diet and HDL L. paracasai B21060
and prebiotics
(arabinogalactan,
xylooligosaccharides)
Ramon- RCT 6 months PWS, 4.5–18 years 28 Probiotic Placebo Improved adiposity, B. animalis 1010 CFU Unknown
Krauel fasting insulin,
et al. HOMA IR, social
(2019) withdrawal
Safavi et al. RCT 8 weeks Ages 6–18, BMI >85% 70 Synbiotic Placebo Synbiotics decreased Protexin synbiotic Plated and

7
(2013) in BMI, waist capsules: 2 · 108 CFU colony count
circumference, waist (L. casei, L. rhamnosus, by expert
to hip ratio, TG, S. thermophilus,
cholesterol. B. breve, L. acidophilus,
B. longum, L. bulgaricus)
+ prebiotic, and
vitamins.
Vajro et al. DBPC 8 weeks Obese children w/ 20 Probiotic Placebo Decrease in ALT L. rhamnosus GG
(2011) Pilot hypertransaminasemia (12 billion CFU/day)
and U/S bright liver
Videhult RCT 9 months Healthy NB age 4–13 120 Cereal (rice from Cereal without LF19 had no effect L. paracasei
et al. months followed up at 4 to 6 months, probiotic on body ssp. paracasei F19
(2015) 8–9 years old wheat from 6 to composition, (LF19) 108 CFU
13 months)+ metabolic, or
probiotic inflammatory
markers at school-
age follow-up
DBPC, double blinded placebo controlled; NAFLD, non-alcoholic fatty liver disease; PRCC, prospective, randomized, case–control study; RCT, randomized controlled trial.
 Downloaded by Morocco Hinari Band 2 from www.liebertpub.com at 11/08/22. For personal use only.

Table 2. Outcomes
Anthropometric Inflammatory Hepatic
measures markers Lipid markers Glucose metabolism measures Diet related
Other
Outcome Waist Fatty Liver Microbiome Dietary Appetite
variables Study BMI Adiposity circ TNFa IL-6 LPS CRP TG LDL TC HDL GLC Insulin HOMA GLP1 liver enzymes D intake hormones BP
Benefit Alisi et al. (2014) Y 4 4 [ Y 4
Amat-Bou et al. 4 Y 4 4 4 4 4 Y Y 4 4 4
(2020)
Chen et al. (2019) Y Y Y Y Y Y Y Y
Famouri et al. 4 Y Y Y Y Y
(2017)
Gombert et al. Y Y [ [
(2019)
Goyal et al. Y Y Y Y [ Y Y Y Y
(2019)
Herrera et al. 4 4 Y Y
(2018)
Kelishadi (2014) Y Y 4
Kianifar et al. Y Y Y
(2018)

8
Larsen et al. [
(2013)
Mandato and 4 4 Y
colleagues (2011)
Miccheli et al. Y [ Y Y
(2015)
Passariello (2016) Y Y
Ramon-Krauel 4 Y 4* Y Y 4 4
et al. (2019)
Safavi et al. (2013) Y Y Y Y Y
Vajro et al. (2011) 4 4 Y
None Gøbel et al. 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4
(2012)
Videhult et al. 4 4 4 4 4 4 4 4 4 4 4 4
(2015)
Adverse Jones et al. (2018) [ 4 4 4 4

*No change in lipids, parameters unspecified.

Y = decrease; [ = increase; 4 = no change; [blank] = not evaluated.
BMI, body mass index; Waist Circ, waist circumference; TNF alpha, tumor necrosis factor alpha; IL-6, interleukin 6; LPS, lipopolysaccharide; CRP, C-reactive protein; TG, triglyceride; LDL, low-density lipoprotein; TC,
total cholesterol; HDL, high-density cholesterol; GLC, glucose; HOMA, homeostatic model assessment for insulin resistance; GLP1, glucagon-like peptide-1; Microbiome D, microbiome change; BP, blood pressure.
 CHILDHOOD OBESITY MONTH 2022
CECT 7765 (10 CFU), and Protexin synbiotic combination
(L. casei, L. rhamnosus, S. thermophilus, B. breve, L. acid-
ophilus, B. longum, L. bulgaricus, Fructo Oligosaccharide
prebiotics, vitamin E, A, C.). The duration of probiotics
ranged from 8 weeks to 16 weeks. Secondary beneficial out-
comes reported included improvement in inflammatory
markers, triglycerides, lipid markers, glucose metabolism,
insulin markers, fatty liver, and microbiome shifts.
Overall, of the 19 studies included, 16 studies showed
benefits for probiotic supplementation as it relates to obe-
sity or weight-related conditions. Two other studies showed
no effect,20,21 and one showed a negative effect.22
Obesity Treatment–No Effect or Negative Effect
Besides the one study on prevention that showed no
Downloaded by Morocco Hinari Band 2 from www.liebertpub.com at 11/08/22. For personal use only.
effect in young children, study in adolescents21 showed
no changes in anthropometric measures, inflammation,
and stool in adolescents with metabolic syndrome given
probiotics.
There was one study out of the 19 included studies, in
which probiotic use was associated with negative effects–
increased total and trunk adiposity. However, there were
no significant effects on liver fat, insulin glucose, gut
microbiome, and hormones.22
Clinical Trials
To ascertain ongoing efforts, we conducted a scoping
review of clinical trials using the same criteria. Of the 100
clinical trials screened, 9 met initial criteria. While results
were not available, the majority of the interventions
planned to use probiotics alone. A variety of probiotics
were specified, including L. salivarius (1), VSL (3), and
combinations (5). Specified strains included L. rhamno-
sus, B. animalis, L. salivarius, B. breve, B. bifidum, B.
longum, enterococcus, Culturelle, L. acidophilus, L.
plantarum, L. paracasei, L. bulgaricus, and S. thermo-
philus. Some of the markers or endpoints being assessed
were similar to those in our scoping review and included
weight, obesity parameters, insulin resistance, glucose
metabolism, lipid metabolism, gut microbiome diversity,
and inflammatory parameters. Two trials planned to
measure stool colonization through 16sRNA.While it is
our hope that some of the outstanding questions can be
addressed by these trials, heterogeneity in species and
strains used is noted, similar to our findings in the scoping
review.
While we only included full-text publications, it should
be noted that there were a number of abstracts reporting
promising findings supporting BMI, anthropometric mea-
sures, lipid, metabolic, and glucose improvements in
children and adolescents with obesity (Belei 2019, Solito
2018, Prodam 2020).
We examined the funding sources for all the included
articles and clinical trials, and there was no significant
trend or common funding source. No funding was used for
this scoping review.
9
Discussion
To our knowledge, there has not been a scoping review
or systematic review published on the use of probiotics in
the prevention and treatment of obesity in children and
adolescents with overweight or obesity or those with
weight-related conditions other than NAFLD.
Probiotics Use in NAFLD
A number of systematic reviews and meta-analyses have
been published on the use of probiotics for NAFLD.34–37
Most confirm heterogeneous outcomes in adults, with very
few studies on children or adolescents. For example, pro-
biotics provided improvements in outcomes in homeostasis
model assessment, total cholesterol, high-density lipopro-
tein, and tumor necrosis factor in NAFLD patients and
triglycerides in Italian and Spanish patients, but no im-
provement in the outcomes of BMI, glucose, or insulin in
adult NAFLD patients.34
A 2019 meta-analysis that included both adult and pedi-
atric populations confirmed probiotics may improve BMI,
liver enzymes, and hyperglycemia in NAFLD. However,
insufficient number of pediatric studies along with the
heterogeneity of study designs led them to conclude that
the effect of probiotics in BMI among children with
NAFLD is still unclear (Xiao, 2019). Sharpton et al. also
concluded in 2019 that there is general paucity of studies of
probiotics in Pediatric NAFLD. Out of 21 studies of pro-
biotics or synbiotics in NAFLD, only three were conducted
in children, and they were all probiotic-only studies.26,32,38
Probiotics and synbiotics were associated with a significant
reduction in BMI, although this effect was predominantly
driven by probiotic and not synbiotic trials. Twelve trials
involved synbiotics, but none of these trials was performed
in children. Probiotics were associated with favorable liver
parameters and BMI, but not insulin resistance or triglyc-
erides. There were no meaningful differences in the effi-
cacy of probiotics among children and adults with NAFLD,
although this comparison was limited by the relative
paucity of trials examining probiotics in the pediatric
population.36,37
Probiotics and Pediatric NAFLD
A review of pediatric studies26,32,38,39 concluded that a
limited course of probiotics in conjunction with lifestyle
changes could be effective in improving pediatric NAFLD.
However, overall evidence was low due to small sample
size, different probiotic strains, short duration of trial
and follow-up, and lack of histologic endpoint outcomes.35
The 2018 TES Obesity Management Science Statement
did not recommend probiotics to treat obesity, which may
result from the strain-specific actions of probiotics and
varied individual response in BMI. The role of probio-
tics in reducing BMI in adult patients with NAFLD
seemed promising, but more clinical evidence is needed in
children.37
 10
Probiotics on Prevention and Treatment of Obesity
This scoping review found there is no evidence for the
use of probiotics in the prevention of obesity, and hetero-
geneous evidence for the use of probiotics in the treatment
of obesity in children and adolescents with overweight or
obesity and those with weight-related conditions. Studies
also indicate potential benefits in BMI, adiposity, metabolic
parameters, inflammatory markers, fatty liver, transami-
nases, and glucose metabolism in overweight or obese
children and adolescents.
While the goal of a scoping review is not to examine the
efficacy of the interventions, to help understand the find-
ings in context there are three studies that provide some
reference to the scale of improvements.
Kianifar et al. in 2019 reported a BMI z score decrease
from 2.1 to 1.88 ( p < 0.001) and % body fat decrease from
Downloaded by Morocco Hinari Band 2 from www.liebertpub.com at 11/08/22. For personal use only.
34.4% to 31% ( p < 0.001) over the 12 weeks of synbiotic
intervention. Miccheli et al. in 2015 reported a decrease
in BMI from 26.9 to 24.6 over 4 months ( p = 0.05) in the
VSL intervention group. Safavi et al. in 2013 reported a
difference in the BMI z score of .09 – 0.01 ( p < 0.0001)
(synbiotic group) versus 0.2 – 0.01 in the ( p = 0.032) (pla-
cebo group). However, most of the other studies only re-
ported statistical significance without providing magnitude
data.
It is difficult to make interpretations on the significance
on the limited magnitude data that exists as accepted
standards are lacking. Treatment in pediatric weight man-
agement programs was associated with median decreases
in BMI as measured by change in % of the 95th percentile
for BMI (%BMIp95) of -1.88 (at 4–6 months follow-up)
and -2.86 (at 10–12 months follow-up). A 5% point
decrease in %BMIp95 was associated with improvement in
cardiometabolic risk factors.40 We suggest a call to action
for obesity researchers to delineate magnitude standards
for what outcomes would be considered a significant
clinical (not just statistical) outcome.
Heterogeneity in Literature
The strains of probiotics used were heterogeneous.
The trials used a variety of probiotic interventions,
including VSL#3 (5), Lactobacillus, Streptococcus, Bi-
fidobacterium combination strains + synbiotics (1),
Lactobacillus combination strains and Bifidobacterium
combination strains (1), Lactobacillus of varying strains
(4), Bifidobacterium of varying strains (4), and prebiotic
combined with varying probiotics (5). All but one indicated
CFU values. The probiotic interventions were heteroge-
neous in administration form (capsule, sachet, packet,
drink), preparations (combinations with prebiotics, vitamins,
liquids containing erythritol and stevia, protein drink),
varying dietary recommendations (reduced calorie pre-
scription, fruit and vegetable emphasis, very-low carbohy-
drate diet, various cereals), and physical activity
recommendations (aerobic, lifestyle modification). A subset
of studies examined the stool microbiome, and 4 confirmed
with 16S PCR technology.21,22,31,41
LOY ET AL.
Future Research
To enhance reproducibility of clinical intervention stud-
ies in children and adolescents, rigorous and detailed
documentation of specific probiotic strains, documented
properties, and potential interaction with food matrix/
nutrients are necessary. In addition, questions such as
whether the probiotic is characterized by genomic studies,
and issues such as specific dose, temporal relationship
between probiotic intake and health impact, dose/response
relationship, validated markers relevant to the disease,
cessation of probiotic exposure impact on health outcome,
consistency and specificity of association, and evidence
for causality, all need to be considered.42
Well-designed randomized placebo-controlled human
intervention studies that are replicated and then subjected
to a meta-analysis or comprehensive review would be
ideal. Varying host factors include genetics, mode of pro-
biotic delivery, type of microbiota, underlying health,
duration of breastfeeding, colonization process, compli-
ance or adherence to study intervention will affect out-
comes. Varying probiotic factors include strains varying
by product type, dose, administration time, viability, and
absorption will also contribute to heterogeneous results.
The challenges of controlling for varying host and probi-
otic factors are admittedly significant challenges.
Limitations of the Field
The assessment of pro- and prebiotic effects in humans
is far more complex than other standardized experimental
conditions because different confounding factors, includ-
ing varying host factors, probiotic factors, antibiotic use,
background diet, activity levels, endotoxin content of food,
meal size, and frequency may affect gut microbiota, energy
balance, and ultimately body weight.43–52
Limitations of the Scoping Review
In our scoping review, the intervention groups differed in
accompanying diet, physical activity, caloric intake, and
administration form of probiotic (mixed with food, pill,
powder, protein drink, fruit/vegetable intake). A lack of
standardization in the formulation, viability, and diversity of
probiotic interventions employed by the different studies may
also result in confounding. Complex existing data, including
doses, durations, formulations, and combination of treatment
are difficult to reconcile. Future studies would ideally be
designed to isolate the impact of probiotics alone as com-
pared with the use in combination with other treatments.
One final limitation of this scoping review is that liter-
ature published in languages other than English were not
assessed, which can result in selection bias.
Summary of Literature
Despite these limitations, this scoping review provides
an in-depth assessment of the effect of probiotics in chil-
dren and adolescents who are overweight or obese and
those with weight-related conditions other than NAFLD.
In spite of the complex data, results from the scoping
 CHILDHOOD OBESITY MONTH 2022
review show promise for probiotic use in the treatment of
pediatric overweight and obesity. There are also potential
secondary benefits in the areas of inflammation, glucose
metabolism, body composition, lipid markers, hepatic
enzymes, and social withdrawal. From a practical stand-
point, while awaiting well-designed RCTs with clinical
endpoints, the importance of healthy lifestyle in its broader
sense, including breast lactation, a healthy fiber-rich diet,
and avoidance of inappropriate antibiotic use, cannot be
overemphasized and may ensure a friendly gut microbiota,
positively affecting metabolic outcomes.
Conclusion
In our scoping review of published and actively ongoing
randomized controlled trials of children and adolescents
Downloaded by Morocco Hinari Band 2 from www.liebertpub.com at 11/08/22. For personal use only.
who are overweight, obese, or have weight-related condi-
tions other than NAFLD, we found some evidence for the
use of probiotics in obesity treatment but not in prevention.
There was a large amount of heterogeneity in study end-
points and inclusion criteria. Few trials included stool
analyses. Probiotics appear to improve BMI, liver trans-
aminase levels, inflammatory markers, metabolic markers,
and shift the microbiome, but results were heterogeneous.
Effects of treatment using probiotics (with or without
prebiotics) with children and adolescents who are over-
weight, obese, or have weight-related conditions other than
NAFLD have not been systematically studied nor validated
with stool confirmation by PCR. Trials that are underway
to further address these questions are anticipated.
Authors’ Contributions
M.H.L. contributed to the design of the research, con-
tributed to the implementation of the research, drafted the
initial article, reviewed, and revised the article. M.A.G.
conceptualized and designed the study, contributed to the
implementation of the research, and reviewed and revised
the article. J.U. contributed to the design of the research
and the implementation of the research. D.L. contributed
to the implementation of the research. All authors appro-
ved the final article as submitted and agree to be account-
able for all aspects of the work.
Author Disclosure Statement
No competing financial interests exist.
Funding Information
No funding was received for this article.
References
1. Kumar S, Kelly AS. Review of childhood obesity: From epide-
miology, etiology, and comorbidities to clinical assessment and
treatment. Mayo Clin Proc 2017;92:251–265.
11
2. Goldin BR, Gorbach SL. Clinical indications for probiotics: An
overview. Clin Infect Dis 2008;46(SUPPL. 2 PG-S96-S100):S96–
S100.
3. Benninga MA, Vink M, Akkermans LMA, et al. Intestinal Microbiota
and Its Role in the Development of Paediatric Gastrointestinal Dis-
orders. The Netherlands: Wageningen Academic Publishers, 2017.
4. Mazzola G, Aloisio I, Di Gioia D, et al. Infant Development,
Currently the Main Applications of Probiotics and Prebiotics?.
Poole, United Kingdom: Caister Academic, 2015.
5. Cani PD, Delzenne NM. Gut microflora as a target for energy and
metabolic homeostasis. Curr Opin Clin Nutr Metab Care 2007;10:
729–734.
6. Ma X, Hua J, Li Z. Probiotics improve high fat diet-induced
hepatic steatosis and insulin resistance by increasing hepatic NKT
cells. J Hepatol 2008;49:821–830.
7. Yin YN, Yu QF, Fu N, et al. Effects of four Bifidobacteria on
obesity in high-fat diet induced rats. World J Gastroenterol 2010;
16:3394–3401.
8. Moya-Pérez A, Neef A, Sanz Y. Bifidobacterium pseudocatenu-
latum CECT 7765 reduces obesity-associated inflammation by
restoring the lymphocyte-macrophage balance and gut microbiota
structure in high-fat diet-fed mice. PLoS One 2015;10:e0126976.
9. Blaut M, Bischoff SC. Probiotics and obesity. Ann Nutr Metab
2010;57 Suppl:20–23.
10. Kalliomäki M, Collado MC, Salminen S, Isolauri E. Early differ-
ences in fecal microbiota composition in children may predict
overweight. Am J Clin Nutr 2008;87:534–538.
11. Million M, Maraninchi M, Henry M, et al. Obesity-associated gut
microbiota is enriched in Lactobacillus reuteri and depleted in
Bifidobacterium animalis and Methanobrevibacter smithii. Int J
Obes (Lond) 2012;36:817–825.
12. Schwiertz A, Jacobi M, Frick J-S, et al. Microbiota in pediatric
inflammatory bowel disease. J Pediatr 2010;157:240–244.e1.
13. Collado MC, Donat E, Ribes-Koninckx C, et al. Imbalances in
faecal and duodenal Bifidobacterium species composition in active
and non-active coeliac disease. BMC Microbiol 2008;8:232.
14. Colquhoun HL, Levac D, O’Brien KK, et al. Scoping reviews:
Time for clarity in definition, methods, and reporting. J Clin
Epidemiol 2014;67:1291–1294.
15. Pham MT, Rajić A, Greig JD, Sargeant JM, Papadopoulos A,
Mcewen SA. A scoping review of scoping reviews: Advancing the
approach and enhancing the consistency. Res Synth Methods 2014;
5:371–385.
16. Nyanchoka L, Tudur-Smith C, Thu VN, et al. A scoping review
describes methods used to identify, prioritize and display gaps in
health research. J Clin Epidemiol 2019;109:99–110.
17. Arksey H, O’Malley L. Scoping studies: Towards a methodological
framework. Int J Soc Res Methodol Theory Pract 2005;8:19–32.
18. Tricco AC, Lillie E, Zarin W, et al. PRISMA Extension for
Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann
Intern Med 2018;169:467–473.
19. McHugh ML. Lessons in biostatistics interrater reliability: The
kappa statistic. Biochem Med 2012;22:276–282.
20. Videhult FK, Andersson Y, Ohlund I, et al. Impact of probiotics
during weaning on the metabolic and inflammatory profile:
Follow-up at school age. Int J Food Sci Nutr 2015;66(6 PG-686-
691):686–691.
21. Gøbel RJ, Larsen N, Jakobsen M, et al. Probiotics to adolescents
with obesity: Effects on inflammation and metabolic syndrome.
J Pediatr Gastroenterol Nutr 2012;55:673–678.
22. Jones RB, Alderete TL, Martin AA, et al. Probiotic supplemen-
tation increases obesity with no detectable effects on liver fat or
 12
gut microbiota in obese Hispanic adolescents: A 16-week, ran-
domized, placebo-controlled trial. Pediatr Obes 2018;13(11 PG-
705-714):705–714.
23. Miccheli A, Capuani G, Marini F, et al. Urinary 1 H-NMR-based
metabolic profiling of children with NAFLD undergoing VSL#3
treatment. Int J Obes 2015;39(7 PG-1118-1125):1118–1125.
24. Chen R, Ai Z, Yang X, et al. Effect of probiotics intake on
obese children. Horm Res Paediatr 2019;91(PG-222-223):222–223.
25. Gombert M, Sanchis Chorda J, Gomez Del Pulgar E, et al.
Improvement of chronic inflammation in obese children consecu-
tive to probiotic intake. Obes Facts 2019;12(PG-119):119.
26. Alisi A, Bedogni G, Baviera G, et al. Randomised clinical trial: The
beneficial effects of VSL#3 in obese children with non-alcoholic
steatohepatitis. Aliment Pharmacol Ther 2014;39:1276–1285.
27. Goyal P, Thapa BR, Sharma NR, Bhatia A. Probiotic and lifestyle
modification in obese pediatrics with non-alcoholic fatty liver
disease. Indian J Community Heal 2019;31(1 SE-Original Article):
Downloaded by Morocco Hinari Band 2 from www.liebertpub.com at 11/08/22. For personal use only.
50–56.
28. Safavi M, Farajian S, Kelishadi R, et al. The effects of synbiotic
supplementation on some cardio-metabolic risk factors in over-
weight and obese children: A randomized triple-masked controlled
trial. Int J Food Sci Nutr 2013;64:687–693.
29. Herrera L, Strong D, Knight R, Rhee K. Effect of probiotics and
dietary changes on inflammatory markers and adiposity in chil-
dren. Gastroenterology 2018;154(6 PG-S-200):S-200.
30. Ramon-Krauel M, Amat-Bou M, Garcı́a-Rivera S, et al. Effects
of Bifidobacterium animalis subsp. lactis on children with Prader-
Willi syndrome: A randomized, double-blind, placebo-controlled,
crossover trial. Horm Res Paediatr 2019;91(PG-67-68):67–68.
31. Amat-Bou M, Garcia-Ribera S, Climent E, et al. Effects of
Bifidobacterium animalis Subsp. lactis (BPL1) Supplementation
in Children and Adolescents with Prader-Willi Syndrome: A
Randomized Crossover Trial. Nutrients 2020;12:3123.
32. Famouri F, Shariat Z, Hashemipour M, et al. Effects of probiotics
on nonalcoholic fatty liver disease in obese children and adoles-
cents. J Pediatr Gastroenterol Nutr 2017;64:413–417.
33. Kianifar HR, Ahanchian H, Safarian M, et al. Effects of synbiotics
on anthropometric indices of obesity in children: A randomized
double-blind placebo-controlled pilot study. Top Clin Nutr 2018;
33:118–126.
34. Kelishadi R, Farajian S, Safavi M, et al. A randomized triple-
masked controlled trial on the effects of synbiotics on inflamma-
tion markers in overweight children. J Pediatr (Rio J) 2014;90:
161–168.
35. Passariello A, Malamisura M, Leone L, et al. Positive effect of
a new symbiotic formulation containing lactobacillus paracasei
B21060 in children with familial hypercholesterolemia. J Clin
Gastroenterol 2016;50:S218–S219.
36. Gao X, Zhu Y, Wen Y, et al. Efficacy of probiotics in non-
alcoholic fatty liver disease in adult and children: A meta-analysis
of randomized controlled trials. Hepatol Res 2016;46:1226–1233.
37. Sansotta N, Peroni DG, Romano S, et al. The good bugs: The use
of probiotics in pediatrics. Curr Opin Pediatr 2019;31(5 PG-661-
669):661–669.
38. Sharpton SR, Maraj B, Harding-Theobald E, et al. Gut
microbiome-targeted therapies in nonalcoholic fatty liver disease:
A systematic review, meta-analysis, and meta-regression. Am J
Clin Nutr 2019;110(1 PG-139-149):139–149.
39. Xiao MW, Lin SX, Shen ZH, et al. Systematic review with meta-
analysis: The effects of probiotics in nonalcoholic fatty liver dis-
ease. Gastroenterol Res Pract 2019;2019(PG-):1484598.
LOY ET AL.
40. Vajro P, Mandato C, Licenziati MR, et al. Effects of Lactobacillus
rhamnosus strain GG in pediatric obesity-related liver disease.
J Pediatr Gastroenterol Nutr 2011;52:740–743.
41. Nobili V, Sanyal AJ. Treatment of nonalcoholic fatty liver disease
in adults and children: A closer look at the arsenal. J Gastroenterol
2012;47(1 PG-29-36):29–36.
42. Kumar S, King EC, Christison AL, et al. Health outcomes of youth
in clinical pediatric weight management programs in POWER.
J Pediatr 2019;208:57–65.e4.
43. Larsen N, Vogensen FK, GÃ xbel RJ, et al. Effect of Lactobacillus
salivarius Ls-33 on fecal microbiota in obese adolescents. Clin
Nutr 2013;32(6 PG-935-940):935–940.
44. Isolauri E, Salminen S. The impact of early gut microbiota mod-
ulation on the risk of child disease: Alert to accuracy in probiotic
studies. Benef Microbes 2015;6(2 PG-167-171):167–171.
45. Musso G, Gambino R, Cassader M. Obesity, diabetes, and gut
microbiota: The hygiene hypothesis expanded? Diabetes Care
2010;33(10 PG-2277-2284):2277–2284.
46. Amar J, Burcelin R, Ruidavets JB, et al. Energy intake is associ-
ated with endotoxemia in apparently healthy men. Am J Clin Nutr
2008;87:1219–1223.
47. Deopurkar R, Ghanim H, Friedman J, et al. Differential effects of
cream, glucose, and orange juice on inflammation, endotoxin, and
the expression of Toll-like receptor-4 and suppressor of cytokine
signaling-3. Diabetes Care 2010;33:991–997.
48. Ghanim H, Sia CL, Upadhyay M, et al. Orange juice neutralizes
the proinflammatory effect of a high-fat, high-carbohydrate meal
and prevents endotoxin increase and Toll-like receptor expression.
Am J Clin Nutr 2010;91:940–949.
49. Palmer C, Bik EM, DiGiulio DB, et al. Development of the human
infant intestinal microbiota. PLoS Biol 2007;5:e177.
50. Penders J, Thijs C, Vink C, et al. Factors influencing the compo-
sition of the intestinal microbiota in early infancy. Pediatrics 2006;
118:511 LP–521.
51. Penders J, Vink C, Driessen C, et al. Quantification of Bifido-
bacterium spp., Escherichia coli and Clostridium difficile in faecal
samples of breast-fed and formula-fed infants by real-time PCR.
FEMS Microbiol Lett 2005;243:141–147.
52. Nilsson AC, Ostman EM, Holst JJ, Björck IME. Including indi-
gestible carbohydrates in the evening meal of healthy subjects
improves glucose tolerance, lowers inflammatory markers, and
increases satiety after a subsequent standardized breakfast. J Nutr
2008;138:732–739.
53. Luoto R, Kalliomäki M, Laitinen K, Isolauri E. The impact of
perinatal probiotic intervention on the development of overweight
and obesity: Follow-up study from birth to 10 years. Int J Obes
(Lond) 2010;34:1531–1537.
54. Crawford PA, Crowley JR, Sambandam N, et al. Regulation of myo-
cardial ketone body metabolism by the gut microbiota during nutrient
deprivation. Proc Natl Acad Sci U S A 2009;106:11276–11281.
Address correspondence to:
Michelle Loy, MD
Department of Pediatrics
Weill Cornell Medicine
436 East 69th Street
New York, NY 10065
USA
E-mail: mhloy@med.cornell.edu
(Appendix follows /)
 CHILDHOOD OBESITY MONTH 2022
Appendix A1. Search Strategy
Updated March 4, 2021
Search Strategy Document – FINAL 2/27/2020 Data-
bases: PubMed – 128 results (2/27/2020) Ovid MEDLINE
– 124 results (2/27/2020) Cochrane Library/CENTRAL –
294 results (2/27/2020) Embase – 898 results (2/27/2020)
CINAHL – 30 results (2/27/2020) ClinicalTrials.gov – 293
results (2/27/2020) Scopus – 61 results (2/27/2020) Web of
Science – 133 results (2/27/2020) PubMed Date Searched:
2/27/2020 Number of Results: 128 Search Strategy:
((‘‘Infant’’[Mesh] OR ‘‘Child’’[Mesh] OR ‘‘Ado-
lescent’’[Mesh]) OR Infant[tiab] OR pediatric*[tiab] OR
child[tiab] OR children[tiab] OR adolescent*[tiab] OR
Downloaded by Morocco Hinari Band 2 from www.liebertpub.com at 11/08/22. For personal use only.
teen*[tiab]) AND ((‘‘Overweight’’[Mesh] OR ‘‘Diabetes
Mellitus, Type 2’’[Mesh] OR ‘‘Insulin Resistance’’[Mesh]
OR ‘‘Hypertension’’[Mesh] OR ‘‘Non-alcoholic Fatty
Liver Disease’’[Mesh] OR ‘‘Sleep Apnea Syn-
dromes’’[Mesh] OR ‘‘Dyslipidemias’’[Mesh] OR
‘‘Inflammation’’[Mesh] OR ‘‘Hypercholester-
olemia’’[Mesh] OR ‘‘Polycystic Ovary Syndrome’’[Mesh]
OR ‘‘Acanthosis Nigricans’’[Mesh]) OR Overweight[tiab]
OR obese[tiab] OR obesity[tiab] OR ‘‘type 2 diabe-
tes’’[tiab] OR ‘‘insulin resistance’’[tiab] OR hyperten-
sion[tiab] OR ‘‘nonalcoholic fatty liver disease’’[tiab] OR
‘‘NAFLD’’[tiab] OR ‘‘sleep apnea’’[tiab] OR dyslipide-
mia[tiab] OR ‘‘metabolic syndrome’’[tiab] OR inflamma-
tion[tiab] OR hypercholesterolemia[tiab] OR ‘‘polycystic
ovary syndrome’’[tiab] OR ‘‘polycystic ovarian syn-
drome’’[tiab] OR ‘‘PCOS’’[tiab] OR ‘‘acanthosis nigri-
cans’’[tiab]) AND ((‘‘Probiotics’’[Mesh] OR
‘‘Lactobacillus’’[Mesh] OR ‘‘Lactococcus’’[Mesh] OR
‘‘Bifidobacterium’’[Mesh] OR ‘‘Propionibacter-
ium’’[Mesh] OR ‘‘Streptococcus’’[Mesh] OR ‘‘Bacter-
oides’’[Mesh]) OR Probiotic*[tiab] OR ‘‘VSL3’’[tiab] OR
‘‘VSL#3’’[tiab] OR ‘‘VSL 3’’[tiab] OR ‘‘VSL #3’’[tiab]
OR ‘‘VSL# 3’’[tiab] OR lactobacillus[tiab] OR lacto-
coccus[tiab] OR bifidobacterium[tiab] OR propioni-
bacterium[tiab] OR streptococcus[tiab] OR
Bacteroides[tiab] OR vivomixx[tiab]) AND ((‘‘Place-
bos’’[Mesh]) OR Placebo[tiab]) AND ((‘‘Treatment Out-
come’’[Mesh] OR ‘‘Triglycerides’’[Mesh] OR ‘‘Alanine
Transaminase’’[Mesh] OR ‘‘GlucagonLike Peptide
1’’[Mesh] OR ‘‘Body Mass Index’’[Mesh] OR ‘‘C-
Peptide’’[Mesh] OR ‘‘Cholesterol’’[Mesh] OR ‘‘Fatty
Acids, Nonesterified’’[Mesh] OR ‘‘C-Reactive Pro-
tein’’[Mesh] OR ‘‘Interleukins’’[Mesh] OR ‘‘Tumor Ne-
crosis Factor-alpha’’[Mesh] OR ‘‘Cytokines’’[Mesh] OR
‘‘Lipopolysaccharides’’[Mesh] OR ‘‘Microbiota’’[Mesh]
OR ‘‘Fatty Liver’’[Mesh] OR ‘‘Glycated Hemoglobin
A’’[Mesh] OR ‘‘Glucose Tolerance Test’’[Mesh] OR
‘‘Leptin’’[Mesh] OR ‘‘Plasminogen Activator Inhibitor
1’’[Mesh] OR ‘‘Lipids’’[Mesh] OR ‘‘Body Composi-
13
tion’’[Mesh] OR ‘‘Transaminases’’[Mesh] OR ‘‘Waist
Circumference’’[Mesh] OR ‘‘Waist-Hip Ratio’’[Mesh] OR
‘‘Intra-Abdominal Fat’’[Mesh]) OR Effectiveness[tiab]
OR efficacy[tiab] OR ‘‘fatty liver severity’’[tiab] OR tri-
glyceride*[tiab] OR ‘‘homeostasis model assess-
ment’’[tiab] OR ‘‘HOMA’’[tiab] OR ‘‘alanine
transaminase’’[tiab] OR ‘‘ALT’’[tiab] OR ‘‘glucagon-like
peptide 1’’[tiab] OR ‘‘GLP-1’’[tiab] OR ‘‘aGLP-1’’[tiab]
OR ‘‘body mass index’’[tiab] OR ‘‘BMI’’[tiab] OR
‘‘cpeptide’’[tiab] OR cholesterol[tiab] OR ‘‘free fatty ac-
ids’’[tiab] OR ‘‘FFA’’[tiab] OR ‘‘c-reactive protein’’[tiab]
OR ‘‘CRP’’[tiab] OR interleukins[tiab] OR ‘‘tumor ne-
crosis factor’’[tiab] OR ‘‘TNF’’[tiab] OR cytokines[tiab]
OR ‘‘fasting plasma glucose’’[tiab] OR ‘‘plasma insu-
lin’’[tiab] OR ‘‘lipid profile’’[tiab] OR ‘‘plasma lipopoly-
saccharides’’[tiab] OR ‘‘microbiota’’[tiab] OR ‘‘hepatic
steatosis’’[tiab] OR ‘‘liver steatosis’’[tiab] OR ‘‘glycated
hemoglobin’’[tiab] OR ‘‘hba1c’’[tiab] OR ‘‘a1c’’[tiab] OR
‘‘oral glucose tolerance test’’[tiab] OR ‘‘fat mass’’[tiab]
OR leptin[tiab] OR ‘‘plasminogen activator inhibitor-
1’’[tiab] OR ‘‘high-sensitivity c-reactive protein’’[tiab]
OR ‘‘hsCRP’’[tiab] OR lipids[tiab] OR ‘‘body
composition’’[tiab] OR ‘‘gut composition’’[tiab] OR
transaminase[tiab] OR ‘‘waist circumference’’[tiab] OR
‘‘waist-to-hip ratio’’[tiab] OR ‘‘visceral adiposity’’[tiab])
Ovid MEDLINE Date Searched: 2/27/2020 Number of
Results: 124 Search Strategy: Cochrane Library (inc.
CENTRAL) Date Searched: 2/27/2020 Number of Results:
294 Search Strategy: Embase Date Searched: 2/27/2020
Number of Results: 838 Search Strategy: (‘infant’/exp OR
‘child’/exp OR ‘adolescent’/exp OR infant:ti,ab OR pedi-
atric*:ti,ab OR child:ti,ab OR children:ti,ab OR adoles-
cent*:ti,ab OR teen*:ti,ab) AND (‘obesity’/exp OR ‘non
insulin dependent diabetes mellitus’/exp OR ‘insulin
resistance’/exp OR ‘hypertension’/exp OR ‘nonalcoholic
fatty liver’/exp OR ‘sleep disordered breathing’/exp OR
‘dyslipidemia’/exp OR ‘inflammation’/exp OR ‘hyper-
cholesterolemia’/exp OR ‘ovary polycystic disease’/exp
OR ‘acanthosis nigricans’/exp OR overweight:ti,ab OR
obese:ti,ab OR obesity:ti,ab OR ‘type 2 diabetes’:ti,ab OR
‘insulin resistance’:ti,ab OR hypertension:ti,ab OR ‘non-
alcoholic fatty liver disease’:ti,ab OR ‘nafld’:ti,ab OR
‘sleep apnea’:ti,ab OR dyslipidemia:ti,ab OR ‘metabolic
syndrome’:ti,ab OR inflammation:ti,ab OR hypercholes-
terolemia:ti,ab OR ‘polycystic ovary syndrome’:ti,ab OR
‘polycystic ovarian syndrome’:ti,ab OR ‘pcos’:ti,ab OR
‘acanthosis nigricans’:ti,ab) AND (‘probiotic agent’/exp
OR ‘lactobacillus’/exp OR ‘lactococcus’/exp OR ‘bifido-
bacterium’/exp OR ‘propionibacterium’/exp OR ‘strepto-
coccus’/exp OR ‘bacteroides’/exp OR probiotic*:ti,ab OR
‘vsl3’:ti,ab OR ‘vsl#3’:ti,ab OR ‘vsl 3’:ti,ab OR ‘vsl
#3’:ti,ab OR ‘vsl# 3’:ti,ab OR lactobacillus:ti,ab OR
lactococcus:ti,ab OR bifidobacterium:ti,ab OR
(Appendix continues /)
 14
propionibacterium:ti,ab OR streptococcus:ti,ab OR
bacteroides:ti,ab OR vivomixx:ti,ab) AND (‘placebo’/exp
OR placebo:ti,ab) AND (‘treatment outcome’/exp OR
‘triacylglycerol’/exp OR ‘alanine aminotransferase’/exp
OR ‘glucagon like peptide’/exp OR ‘body mass’/exp OR ‘c
peptide’/exp OR ‘cholesterol’/exp OR ‘fatty acid’/exp OR
‘c reactive protein’/exp OR ‘interleukin derivative’/exp
OR ‘tumor necrosis factor’/exp OR ‘cytokine’/exp OR
‘lipopolysaccharide’/exp OR ‘microflora’/exp OR ‘fatty
liver’/exp OR ‘glycosylated hemoglobin’/exp OR ‘glucose
tolerance test’/exp OR ‘leptin’/exp OR ‘plasminogen
activator inhibitor 1’/exp OR ‘lipid’/exp OR ‘body com-
position’/exp OR ‘aminotransferase’/exp OR ‘waist
circumference’/exp OR ‘waist hip ratio’/exp OR ‘intra-
abdominal fat’/exp OR effectiveness:ti,ab OR effica-
cy:ti,ab OR ‘fatty liver severity’:ti,ab OR triglyceride*:
Downloaded by Morocco Hinari Band 2 from www.liebertpub.com at 11/08/22. For personal use only.
ti,ab OR ‘homeostasis model assessment’:ti,ab OR
‘homa’:ti,ab OR ‘alanine transaminase’:ti,ab OR ‘alt’:ti,ab
OR ‘glucagon-like peptide 1’:ti,ab OR ‘glp-1’:ti,ab OR
‘aglp-1’:ti,ab OR ‘body mass index’:ti,ab OR ‘bmi’:ti,ab
OR ‘c-peptide’:ti,ab OR cholesterol:ti,ab OR ‘free fatty
acids’:ti,ab OR ‘ffa’:ti,ab OR ‘c-reactive protein’:ti,ab OR
‘crp’:ti,ab OR interleukins:ti,ab OR ‘tumor necrosis fac-
tor’:ti,ab OR ‘tnf’:ti,ab OR cytokines:ti,ab OR ‘fasting
plasma glucose’:ti,ab OR ‘plasma insulin’:ti,ab OR ‘lipid
profile’:ti,ab OR ‘plasma lipopolysaccharides’:ti,ab OR
‘microbiota’:ti,ab OR ‘hepatic steatosis’:ti,ab OR ‘liver
steatosis’:ti,ab OR ‘glycated hemoglobin’:ti,ab OR
‘hba1c’:ti,ab OR ‘a1c’:ti,ab OR ‘oral glucose tolerance
test’:ti,ab OR ‘fat mass’:ti,ab OR leptin:ti,ab OR ‘plas-
minogen activator inhibitor1’:ti,ab OR ‘high-sensitivity
c-reactive protein’:ti,ab OR ‘hscrp’:ti,ab OR lipids:ti,ab
OR ‘body composition’:ti,ab OR ‘gut composition’:ti,ab
OR transaminase:ti,ab OR ‘waist circumference’:ti,ab OR
‘waist-to-hip ratio’:ti,ab OR ‘visceral adiposity’:ti,ab)
CINAHL Date Searched: 2/27/2020 Number of Results: 30
Search Strategy: ((MH ‘‘Infant’’) OR (MH ‘‘Child’’) OR
(MH ‘‘Adolescence’’) OR (TI ‘‘infant’’) OR (AB ‘‘in-
fant’’) OR (TI ‘‘pediatric*’’) OR (AB ‘‘pediatric*’’) OR
(TI ‘‘child’’) OR (AB ‘‘child’’) OR (TI ‘‘children’’) OR
(AB ‘‘children’’) OR {TI ‘‘adolescent*’’) OR (AB ‘‘ado-
lescent*’’) OR (TI ‘‘teen*’’) OR (AB ‘‘teen*’’)) AND
((MH ‘‘Obesity’’) OR (MH ‘‘Diabetes Mellitus, Type 2’’)
OR (MH ‘‘Insulin Resistance’’) OR (MH ‘‘Hyperten-
sion’’) OR (MH ‘‘Nonalcoholic Fatty Liver Disease’’) OR
(MH ‘‘Sleep Apnea Syndromes’’) OR (MH ‘‘Hyperlipi-
demia’’) OR (MH ‘‘Inflammation’’) OR (MH ‘‘Hyperch-
olesterolemia’’) OR (MH ‘‘Polycystic Ovary Syndrome’’)
OR (MH ‘‘Melanosis’’) OR (TI ‘‘overweight’’) OR (AB
‘‘overweight’’) OR (TI ‘‘obese’’) OR (AB ‘‘obese’’) OR
(TI ‘‘obesity’’) OR (AB ‘‘obesity’’) OR (TI ‘‘type 2 dia-
betes’’) OR (AB ‘‘type 2 diabetes’’) OR (TI ‘‘insulin
resistance’’) OR (AB ‘‘insulin resistance’’) OR (TI
‘‘hypertension’’) OR (AB ‘‘hypertension’’) OR (TI ‘‘non-
alcoholic fatty liver disease’’) OR (AB ‘‘nonalcoholic fatty
LOY ET AL.
liver disease’’) OR (TI ‘‘NAFLD’’) OR (AB ‘‘NAFLD’’)
OR (TI ‘‘sleep apnea’’) OR (AB ‘‘sleep apnea’’) OR (TI
‘‘dyslipidemia’’) OR (AB ‘‘dyslipidemia’’) OR (TI ‘‘met-
abolic syndrome’’) OR (AB ‘‘metabolic syndrome’’) OR
(TI ‘‘inflammation’’) OR (AB ‘‘inflammation’’) OR (TI
‘‘hypercholesterolemia’’) OR (AB ‘‘hypercholester-
olemia’’) OR (TI ‘‘polycystic ovary syndrome’’) OR (AB
‘‘polycystic ovary syndrome’’) OR (TI ‘‘polycystic ovar-
ian syndrome’’) OR (AB ‘‘polycystic ovarian syndrome’’)
OR (TI ‘‘PCOS’’) OR (AB ‘‘PCOS’’) OR (TI ‘‘acanthosis
nigricans’’) OR (AB ‘‘acanthosis nigricans’’)) AND ((MH
‘‘Probiotics’’) OR (MH ‘‘Lactobacillus’’) OR (MH ‘‘Bi-
fidobacterium’’) OR (MH ‘‘Propionibacterium’’) OR (MH
‘‘Streptococcus’’) OR (MH ‘‘Bacteroides’’) OR (TI
‘‘probiotic*’’) OR (AB ‘‘probiotic*’’) OR (TI ‘‘VLS3’’)
OR (AB ‘‘VSL3’’) OR (TI ‘‘VSL#3’’) OR (AN ‘‘VSL#3’’)
OR (TI ‘‘VSL 3’’) OR (AB ‘‘VSL 3’’) OR (TI
‘‘VSL #3’’) OR (AB ‘‘VSL #3’’) OR (TI ‘‘lactobacillus’’)
OR (AB ‘‘lactobacillus’’) OR (TI ‘‘Bifidobacterium’’) OR
(AB ‘‘Bifidobacterium’’) OR (TI ‘‘Propionibacterium’’)
OR (AB ‘‘Propionibacterium’’) OR (TI ‘‘streptococcus’’)
OR (AB ‘‘streptococcus’’) OR (TI ‘‘Bacteroides’’) OR
(AB ‘‘Bacteroides’’) OR (TI ‘‘vivomixx’’) OR (AB
‘‘vivomixx’’)) AND ((MH ‘‘Placebos’’) OR (TI ‘‘place-
bo’’) OR (AB ‘‘placebo’’)) AND ((MH ‘‘Treatment Out-
comes’’) OR (MH ‘‘Triglycerides’’) OR (MH ‘‘Alanine
Aminotransferase’’) OR (MH ‘‘Glucagon-Like Peptide
1’’) OR (MH ‘‘Body Mass Index’’) OR (MH ‘‘C-
Peptide’’) OR (MH ‘‘Cholesterol’’) OR (MH ‘‘C-Reactive
Protein’’) OR (MH ‘‘Interleukins’’) OR (MH ‘‘Tumor
Necrosis Factor’’) OR (MH ‘‘Cytokines’’) OR (MH
‘‘Lipopolysaccharides’’) OR (MH ‘‘Microbiota’’) OR
(MH ‘‘Fatty Liver’’) OR (MH ‘‘Hemoglobin A, Glyco-
sylated’’) OR (MH ‘‘Glucose Tolerance Test’’) OR (MH
‘‘Leptin’’) OR (MH ‘‘Lipids’’) OR (MH ‘‘Body Compo-
sition’’) OR (MH ‘‘Aminotransferases’’) OR (MH ‘‘Waist
Circumference’’) OR (MH ‘‘Waist-Hip Ratio’’) OR (TI
‘‘effectiveness’’) OR (AB ‘‘effectiveness’’) OR (TI ‘‘effi-
cacy’’) OR (AB ‘‘efficacy’’) OR (TI ‘‘fatty liver severity’’)
OR (AB ‘‘fatty liver severity’’) OR (TI ‘‘triglyceride*’’)
OR (AB ‘‘triglyceride*’’) OR (TI ‘‘homeostasis model
assessment’’) OR (AB ‘‘homeostasis model assessment’’)
OR (TI ‘‘HOMA’’) OR (AB ‘‘HOMA’’) OR (TI ‘‘alanine
transaminase’’) OR (AB ‘‘alanine transaminase’’) OR (TI
‘‘ALT’’) OR (AB ‘‘ALT’’) OR (TI ‘‘glucagon-like pep-
tide 1’’) OR (AB ‘‘glucagon-like peptide 1’’) OR (TI
‘‘GLP-1’’) OR (AB ‘‘GLP-1’’) OR (TI ‘‘aGLP-1’’) OR
(AB ‘‘aGLP-1’’) OR (TI ‘‘body mass index’’) OR (AB
‘‘body mass index’’) OR (TI ‘‘BMI’’) OR (AB ‘‘BMI’’)
OR (TI ‘‘c-peptide’’) OR (AB ‘‘c-peptide’’) OR (TI
‘‘cholesterol’’) OR (AB ‘‘cholesterol’’) OR (TI ‘‘free fatty
acids’’) OR (AB ‘‘free fatty acids’’) OR (TI ‘‘FFA’’) OR
(AB ‘‘FFA’’) OR (TI ‘‘c-reactive protein’’) OR (AB
‘‘c-reactive protein’’) OR (TI ‘‘CRP’’) OR (AB ‘‘CRP’’)
OR (TI ‘‘interleukins’’) OR (AB ‘‘interleukins’’) OR (TI
(Appendix continues /)
 CHILDHOOD OBESITY MONTH 2022
‘‘tumor necrosis factor’’) OR (AB ‘‘tumor necrosis fac-
tor’’) OR (TI ‘‘TNF’’) OR (AB ‘‘TNF’’) OR (TI ‘‘cyto-
kines’’) OR (AB ‘‘cytokines’’) OR (TI ‘‘fasting plasma
glucose’’) OR (AB ‘‘fasting plasma glucose’’) OR (TI
‘‘plasma insulin’’) OR (AB ‘‘plasma insulin’’) OR (TI
‘‘lipid profile’’) OR (AB ‘‘lipid profile’’) OR (TI ‘‘plasma
lipopolysaccharides’’) OR (AB ‘‘plasma lipopolysaccha-
rides’’) OR (TI ‘‘microbiota’’) OR (AB ‘‘microbiota’’) OR
(TI ‘‘hepatic steatosis’’) OR (AB ‘‘hepatic steatosis’’) OR
(TI ‘‘liver steatosis’’) OR (AB ‘‘liver steatosis’’) OR (TI
‘‘glycated hemoglobin’’) OR (AB ‘‘glycated hemoglo-
bin’’) OR (TI ‘‘hba1c’’) OR (AB ‘‘hba1c’’) OR (TI ‘‘a1c’’)
OR (AB ‘‘a1c’’) OR (TI ‘‘oral glucose tolerance test’’) OR
(AB ‘‘oral glucose tolerance test’’) OR (TI ‘‘fat mass’’)
OR (AB ‘‘fat mass’’) OR (TI ‘‘leptin’’) OR (AB ‘‘leptin’’)
OR (TI ‘‘plasminogen activator inhibitor-1’’) OR (AB
Downloaded by Morocco Hinari Band 2 from www.liebertpub.com at 11/08/22. For personal use only.
‘‘plasminogen activator inhibitor-1’’) OR (TI ‘‘high-
sensitivity creactive protein’’) OR (AB ‘‘high-sensitivity
c-reactive protein’’) OR (TI ‘‘hsCRP’’) OR (AB
‘‘hsCRP’’) OR (TI ‘‘lipids’’) OR (AB ‘‘lipids’’) OR (TI
‘‘body composition’’) OR (AB ‘‘body composition’’) OR
(TI ‘‘gut composition’’) OR (AB ‘‘gut composition’’) OR
(TI ‘‘transaminase’’) OR (AB ‘‘transaminase’’) OR (TI
‘‘waist circumference’’) OR (AB ‘‘waist circumference’’)
OR (TI ‘‘waist-to-hip ratio’’) OR (AB ‘‘waist-to-hip ra-
tio’’) OR (TI ‘‘visceral adiposity’’) OR (AB ‘‘visceral
adiposity’’)) ClinicalTrials.gov Date Searched: 2/27/2020
Number of Results: - 293 Search Strategy: - Condition or
disease terms: Overweight OR obese OR obesity OR ‘‘type
2 diabetes’’ OR ‘‘insulin resistance’’ OR hypertension OR
‘‘nonalcoholic fatty liver disease’’ OR ‘‘NAFLD’’ OR
‘‘sleep apnea’’ OR dyslipidemia OR ‘‘metabolic syn-
drome’’ OR inflammation OR hypercholesterolemia OR
‘‘polycystic ovary syndrome’’ OR ‘‘polycystic ovarian
syndrome’’ OR ‘‘PCOS’’ OR ‘‘acanthosis nigricans’’
Other terms: Probiotic OR Probiotics OR ‘‘VSL3’’ OR
‘‘VSL#3’’ OR ‘‘VSL 3’’OR ‘‘VSL #3’’ OR ‘‘VSL# 3’’
OR lactobacillus OR lactococcus OR bifidobacterium OR
propionibacterium OR streptococcus OR Bacteroides OR
Vivomixx Final Search Interpreted by database: Probiotic
OR Probiotics OR ‘‘VSL3’’ OR ‘‘VSL#3’’ OR ‘‘VSL
3’’OR ‘‘VSL #3’’ OR ‘‘VSL# 3’’ OR lactobacillus OR
lactococcus OR bifidobacterium OR propionibacterium
OR streptococcus OR Bacteroides OR vivomixx j Over-
weight OR obese OR obesity OR ‘‘type 2 diabetes’’ OR
‘‘insulin resistance’’ OR hypertension OR ‘‘nonalcoholic
fatty liver disease’’ OR ‘‘NAFLD’’ OR ‘‘sleep apnea’’ OR
dyslipidemia OR ‘‘metabolic syndrome’’ OR inflammation
OR hypercholesterolemia OR ‘‘polycyst Scopus Date
Searched: 2/27/2020 Number of Results: 61 Search
Strategy: TITLE-ABS(Infant OR pediatric* OR child
OR children OR adolescent* OR teen*) AND TITLE-
ABS(Overweight OR obese OR obesity OR ‘‘type 2 dia-
betes’’ OR ‘‘insulin resistance’’ OR hypertension OR
‘‘nonalcoholic fatty liver disease’’ OR ‘‘NAFLD’’ OR
‘‘sleep apnea’’ OR dyslipidemia OR ‘‘metabolic syn-
15
drome’’ OR inflammation OR hypercholesterolemia OR
‘‘polycystic ovary syndrome’’ OR ‘‘polycystic ovarian
syndrome’’ OR ‘‘PCOS’’ OR ‘‘acanthosis nigricans’’)
AND TITLE-ABS(Probiotic* OR ‘‘VSL3’’ OR ‘‘VSL#3’’
OR ‘‘VSL 3’’ OR ‘‘VSL #3’’ OR ‘‘VSL# 3’’ OR lacto-
bacillus OR lactococcus OR bifidobacterium OR propio-
nibacterium OR streptococcus OR Bacteroides OR
vivomixx) AND TITLE-ABS(Placebo) AND TITLE-
ABS(Effectiveness OR efficacy OR ‘‘fatty liver severity’’
OR triglyceride* OR ‘‘homeostasis model assessment’’
OR ‘‘HOMA’’ OR ‘‘alanine transaminase’’ OR ‘‘ALT’’
OR ‘‘glucagon-like peptide 1’’ OR ‘‘GLP-1’’ OR ‘‘aGLP-
1’’ OR ‘‘body mass index’’ OR ‘‘BMI’’ OR ‘‘c-peptide’’
OR cholesterol OR ‘‘free fatty acids’’ OR ‘‘FFA’’ OR
‘‘c-reactive protein’’ OR ‘‘CRP’’ OR interleukins OR
‘‘tumor necrosis factor’’ OR ‘‘TNF’’ OR cytokines
OR ‘‘fasting plasma glucose’’ OR ‘‘plasma insulin’’ OR
‘‘lipid profile’’ OR ‘‘plasma lipopolysaccharides’’ OR
‘‘microbiota’’ OR ‘‘hepatic steatosis’’ OR ‘‘liver stea-
tosis’’ OR ‘‘glycated hemoglobin’’ OR ‘‘hba1c’’ OR
‘‘a1c’’ OR ‘‘oral glucose tolerance test’’ OR ‘‘fat mass’’
OR leptin OR ‘‘plasminogen activator inhibitor-1’’ OR
‘‘high-sensitivity c-reactive protein’’ OR ‘‘hsCRP’’ OR
lipids OR ‘‘body composition’’ OR ‘‘gut composition’’
OR transaminase OR ‘‘waist circumference’’ OR ‘‘waist-
to-hip ratio’’ OR ‘‘visceral adiposity’’) Web of Science
Date Searched: 2/27/2020 Number of Results: 133 Search
Strategy: TS = ((Infant OR pediatric* OR child OR chil-
dren OR adolescent* OR teen*) AND (Overweight OR
obese OR obesity OR ‘‘type 2 diabetes’’ OR ‘‘insulin re-
sistance’’ OR hypertension OR ‘‘nonalcoholic fatty liver
disease’’ OR ‘‘NAFLD’’ OR ‘‘sleep apnea’’ OR dyslipi-
demia OR ‘‘metabolic syndrome’’ OR inflammation OR
hypercholesterolemia OR ‘‘polycystic ovary syndrome’’
OR ‘‘polycystic ovarian syndrome’’ OR ‘‘PCOS’’ OR
‘‘acanthosis nigricans’’) AND (Probiotic* OR ‘‘VSL3’’
OR ‘‘VSL 3’’ OR lactobacillus OR lactococcus OR bifi-
dobacterium OR propionibacterium OR streptococcus OR
Bacteroides OR vivomixx) AND (Placebo) AND (Effec-
tiveness OR efficacy OR ‘‘fatty liver severity’’ OR tri-
glyceride* OR ‘‘homeostasis model assessment’’ OR
‘‘HOMA’’ OR ‘‘alanine transaminase’’ OR ‘‘ALT’’ OR
‘‘glucagon-like peptide 1’’ OR ‘‘GLP-1’’ OR ‘‘aGLP-1’’
OR ‘‘body mass index’’ OR ‘‘BMI’’ OR ‘‘c-peptide’’ OR
cholesterol OR ‘‘free fatty acids’’ OR ‘‘FFA’’ OR ‘‘c-
reactive protein’’ OR ‘‘CRP’’ OR interleukins OR ‘‘tumor
necrosis factor’’ OR ‘‘TNF’’ OR cytokines OR ‘‘fasting
plasma glucose’’ OR ‘‘plasma insulin’’ OR ‘‘lipid profile’’
OR ‘‘plasma lipopolysaccharides’’ OR ‘‘microbiota’’ OR
‘‘hepatic steatosis’’ OR ‘‘liver steatosis’’ OR ‘‘glycated
hemoglobin’’ OR ‘‘hba1c’’ OR ‘‘a1c’’ OR ‘‘oral glucose
tolerance test’’ OR ‘‘fat mass’’ OR leptin OR ‘‘plasmino-
gen activator inhibitor-1’’ OR ‘‘high-sensitivity c-reactive
protein’’ OR ‘‘hsCRP’’ OR lipids OR ‘‘body composition’’
OR ‘‘gut composition’’ OR transaminase OR ‘‘waist circum-
ference’’ OR ‘‘waist-to-hip ratio’’ OR ‘‘visceral adiposity’’))