E03: Health Through Gut

Sissi Stove Lorentzen: Hi, my name is Sissi Stove Lorentzen. I am a clinical dietitian nutritionist from
Norway. I've been a delegate for EFAD for the Norwegian Association of Clinical Dietitians since 2013,
and a member of the EFAD's Executive Committee for the last three years.

My daily work is within the field of gastroenterology in an outpatient setting at Lovisenberg Diakonale
Hospital in Oslo. It has been a true pleasure being involved in EFAD’s learning and the new podcast
series.

Sarah Berry: Thank you EFAD for inviting me to join Sissi today. I'm Sarah Berry. I'm a nutritional
scientist at King's College London. And I'm also the Chief Scientist at ZOE, which is a tech company
behind the PREDICT Personalized Nutrition Studies. And my main area of research is all around
personalized nutrition, cardiometabolic health, and postprandial responses, which hopefully, Sissi, we can
dive into a little bit in our chat.

Sissi Stove Lorentzen: Sarah, thank you so much for taking the time to talk to me today. I'm very excited
about this topic, discussing personalized nutrition and its influence on maybe the gut microbiota with you.
But everybody keeps talking about personalization as if it's something really new, but haven’t dieticians
been practicing personalized nutrition for years?

Sarah Berry: Absolutely. So, personalized nutrition and personalized health care have been around since
the day dot. I think the difference here is about the ultimate goal of making this personalization that a
dietitian may be able to give you in a consultation accessible to everyone.

And so, having a one-hour consultation with a dietitian is often expensive or not accessible to everyone,
depending on where you live and what your circumstances are. Also, this evolving area of personalized
nutrition is really capitalizing us well on lots of these novel technologies that allow us to monitor in
real-time, all sorts of biological responses to food, as well as our genetics, our microbiome, and many,
many other phenotypic characteristics that you might not be able to do in a dietetic consultation.

The other thing that I think is really exciting, again, also is that for many people, you might only see a
dietitian if you have a particular illness. And I think personalized nutrition in the way that it's now
evolving is exciting because I think it's something that allows healthy individuals to stay healthy and age
healthily.
Sissi Stove Lorentzen: Exactly. I've been reading some of these articles, and I've been seeing a couple of
definitions. Is there one definition you'd like to use on personalized nutrition? Is there a new one or a
precise one?

Sarah Berry: I don't think there's an agreed definition for personalized nutrition. And often people also
use the term precision nutrition. I think of it as a diet that is personalized to an individual based on a few
factors. And I think of four key factors here.

I think of it based on the individual in terms of what they eat. So, based on the best foods for their
biology. Based on who they are. So, this includes factors such as their genetics, their microbiome, their
age, and their sex, for example.

And then also based on how the individual lives. We have to think of factors such as their culture, their
lifestyle, for example, which factors in lots of different things like how much sleep you've had, what time
of day, and whether you're practicing time-restricted eating.

And lastly, why? Why are people making those dietary choices? And so, I think that it is a diet that's
personalized to someone's biology, but whilst considering the who you are, the what you eat, the how you
eat, and the why you make those dietary choices. That's the definition in my mind of personalized
nutrition where it's not just around what you eat.

Sissi Stove Lorentzen: I totally agree. I think that it's also maybe what's making some clinicians may be
more successful than others because they've started to implement some of that in their daily practice. I'm
sort of interested in, okay, so you've been a researcher, you didn't say exactly how long you've been
researching this, but I was thinking, can you remember the first time you sort of came across this as a
definition?

Sarah Berry: I can't say this kind of one day where suddenly it popped up. You know, I've been
researching for 25 years. For the first 20 years, my research was really around postprandial responses. So,
measuring changes in circulating blood fat and blood glucose and all of the downstream kind of cascade
of events that happens like inflammation, and oxi stress in that immediate eight hours post-consuming
food, which is why we call it postprandial responses.

And that's what I've done for about 20 years and looking at how we can manipulate food structure to
manipulate your postprandial responses because we know they're really important for all sorts of health
outcomes, particularly cardiometabolic health.

I noticed with my research just how variable some of the responses were. So, when you're running RCTs,
the kinds of RCTs I'd been wanting maybe had 20 individuals, and you would see huge variability.
Now typically as nutritional researchers, all we want to do is look, does the mean differ from this
intervention versus that intervention? And I was so preoccupied in my research with does this fact differ
to that fact?

The more I started to actually look at my data and separate out individuals, the more aware I became of
the nuances in just how looking at the group mean, for research isn't actually terribly meaningful in lots of
instances. In some cases, obviously, it is.

And then about five years ago, I had the pleasure of meeting or interacting with Tim Spector, who's a
professor of genetic epidemiology. So, he at that time started a tech healthcare company formed with the
aim of conducting the world's largest personalized nutrition program, called the PREDICT Program
Research, with the goal of producing a personalized nutrition app, which has now recently launched in
both the UK and the US.

And so, right at the beginning of this journey that ZOE embarked on, I was there advising them on how to
run the PREDICT studies, how to design them, to implement them. So, for the last 4 and a half years, I've
been embedded in this world of personalization, and precision nutrition.

Sissi Stove Lorentzen: It’s so fascinating to listen to this. My own start with this was really, I was
working with surgical patients and cancer patients. And I became increasingly aware that so many have
these severe gastrointestinal symptoms, but they also have very bad diets.

So, while I was trying to reduce symptoms and improve maybe bowel function, at the same time, I
gradually also had to try to improve the food quality. And so, you're addressing so many factors - food
intolerance, and maybe other illnesses, weight issues, malnutrition – that's why I became so interested in
that because as a dietitian and to be successful, you really have to have this personalized approach.

Sarah Berry: Exactly! I think that really brings in the 'why'. I said, it's the kind of the what, the who, the
how, and why, which dieticians I think, have a special skill at is the why and do you have a particular
disease? Why do you make those choices, I think is key.

I think what's really exciting from the PREDICT Program of research is that we see amongst even healthy
individuals, about a 20-fold difference in how people respond to exactly the same food. Again, showing
the importance of all of these other factors, we were able to tease apart with the PREDICT Program of
research how much is due to genetics. And we were able to see that actually, genetics only accounts for
less than 50% of the variability that we see in a whole host of different outcomes in response to different
foods. Which again, I think, is really empowering for dietitians because when you're having a
consultation, and people come to you and say, ‘Oh, well, it's all predetermined in my genes’, I think this is
really clear evidence to show it's not predetermined by your genes, that a large proportion of it is
modifiable.

And therefore, by following personalized nutrition advice, whether it's through apps or through
consultations with a dietitian really does have the power to change how you respond to food.

Sissi Stove Lorentzen: Yes, that's exactly why – I mean, I really see that myself, that even my patient
group has the same kind of diet plan when they leave our offices.

So, if we change the focus a little bit here, the last 20 years, maybe even more, there's been like, I would
say, an exponential growth of the interest in the microbiome, and its relation to health and the gut. So, if
we're looking at the microbiome, how can the gut microbiome be influenced by personal nutrition?

Sarah Berry: Yes, I think you're right in saying that this is such an exploding era of research and the
microbiome is something that is at the heart of a lot of the personalized nutrition programs that are out
there and apps that are out there.

So, a lot of companies are focusing either on personalizing based on either your genetics, or based on
your glucose response using continuous glucose monitors, or based on your microbiome.

It all came to a head from a study that was published in 2015 by researchers at the Weizmann Institute in
Israel under the principal investigator, Eran Segal. In 2015, there was a paper that was published by Eran
Segal's team from the Weizmann Institute that I think was a real kind of turning point in this explosion of
personalized nutrition, particularly in relation to the microbiome.

What he did is he measured a whole host of phenotypic characteristics, including the microbiome, to build
prediction algorithms, in order to look at how an individual responds in terms of their blood glucose
response to a given food, and he was be able to predict with about 70% accuracy, using certain input
variables which included the microbiome of an individual's glucose response to any given food.

I think this really was a seminal study, it was the first study to show, 'Hey, do you know what? Precision
nutrition might actually be able to be a fact, not just fiction, But also showing the importance of the
microbiome in these personalized prediction models.'

And since then, with the ZOE PREDICT Studies, we've furthered this to be able to look at what role does
the microbiome play, not just in blood glucose responses, but what's its relationship to a whole host of
other responses - so to circulating blood triglycerides, so lipemic responses, to inflammatory responses?
How does the microbiome differ depending on whether your pre- and post-menopause or how does it
differ depending on how many snacks you have a day, on your diet quality, and so many other factors?
So, I think it's a really exciting area of research. It's something that also is getting cheaper and cheaper to
measure, and simpler to measure. The platforms now that are available for producing some of the
metagenomic sequences are really advanced.

I think that the one thing that we do need to be cautious about is that most studies at the moment are
showing associations. So, they show there's an association between this particular food and these
particular microbes or signature of microbes, which is also associated with this particular pattern of health
outcomes.

Now, what we need to do is we need to get to the next level, I think, we need to be able to show causality.
And this is something we're doing with a new RCT, we're running at ZOE. It’s called the Zoe Method
Studies where we're looking at how we can manipulate the diet to change the microbiome composition,
and looking at subsequent health outcomes. And I think that's what needs to be done now, really, to get
from that fiction to that fact.

Sissi Stove Lorentzen: When you're measuring this, what kind of method are you using to measure the
microbiome because it needs to be, in a way, fast and simple, right? Could you talk a little bit about just
the methodology?

Sarah Berry: I can give you the very top line because I'm not a microbiome specialist by any means. So,
there are two key methods that are used. One is called 16S, which was the typical traditional method that
was used, but it's not very high resolution.

So, for personalized nutrition, I think you need to use a higher resolution technique. There's something
called shotgun metagenomic sequencing, it's just what we're doing for this ZOE PREDICT Studies and is
carried out by our collaborator, Professor Nicola Segata, in Italy.

And it's also about the platform that you use when you're looking at the results. So, there are some very
complex platforms that he has developed, for example, that's identifying each time he upgrades his
platform, hundreds of new bugs that previously just weren't identified.

It's really important that we look at as many of these microbes, but we also need to look at some of the
functional outputs from the microbes, like the short-chain fatty acids, for example, and other metabolites
from the microbiome. So, we need to look at the composition of the microbes, as well as these functional
outputs.

Traditionally, in microbiome research, people have looked at richness or diversity, but I think that
certainly in the world of personalized nutrition, we're realizing the limitations of that as a key metric. And
really, we should be looking again, at those kinds of nuances of the different kinds of microbes, the
prevalence of the different microbes, and again, the kind of functional outputs of these as well.

Sissi Stove Lorentzen: It's so fascinating. I agree with you. It's very complex. When you look at the
names and you look, this is a totally new world, so I'm hoping they're going to have some courses and
classes that will make it easier for us, I would say, lay people, to understand it. You've been talking about
this and how you've been following it in research - how close do you think it's going to be until we can
use it in our daily practice?

Sarah Berry: I can tell you from my own experience working with ZOE, there is a personalized nutrition
app that ZOE have on the market now, which I'm incredibly excited about. It's underpinned by very
high-quality science that we've been conducting with our PREDICT Program of research.

I think that we still have a little way to go. I think that we need to integrate, generally, precision nutrition
a lot more around the how we eat, which is an exciting area that we're now moving into. I think that what
personalized nutrition and these kinds of apps offer is the continuity of follow-up that maybe as a
clinician or a clinical dietitian, is just not possible for you to be in someone's pocket in their home day
after day.

I think this is what's really exciting – it’s marrying up the two so that we can somehow make it work that
if you want to use it in unison when you're leaving your consultation, they have that dietician or that
nutritionist in their pocket supporting them - supporting them in a personalized way, supporting them in
what their goal is, so what it is they want to achieve, supporting them based on how they live their life,
and supporting them based on their dietary choices and also who they are.

Sissi Stove Lorentzen: So, really between the sessions then. So, you would have someone following you,
because I've also had consult patients who have been using the internet or there are some new programs,
and many of them find it very frustrating sometimes because they can't have their questions answered.
But I believe these apps that you're talking about there is actually someone answering the questions all
along, isn't it?

Sarah Berry: Yeah, on the ZOE app, there are nutrition and dietetics coaches. So, it's something we're
really proud of that if anyone has a question, they can type it in the app, and they will get an answer back
immediately.

If it's something that the dietitian can't answer, then it might be escalated to someone else in the team. So,
even as the lead nutritional scientist on this, I'm daily answering questions for our coaches on my specific
areas.
So, for example, to do with dietary fat. So, we're making sure that we're giving the best advice back to
individuals. Now, not all apps do that. I think that ultimately, many of these personalized nutrition
products that are out there are intended to work without the need for someone to go to a healthcare
practitioner or to go to a dietitian, and it depends, again, on the country.

But in the UK, for example, you either spend huge amounts of money to see a dietitian privately, or you
have to have something quite seriously wrong with you to be able to see a dietitian on our NHS. And so,
you have that huge ground in the middle that I think is uncovered. And this is where I think personalized
nutrition apps really can make a difference.

Sissi Stove Lorentzen: Really, you are hitting it spot on because even though I guess my colleagues want
to be everywhere all the time, it's not going to be possible. There are so many people who really need it.
I'm very excited about it. I think there are certain patient groups that you might not be able to use it in a
safe way, but for quite a big group, I agree totally with what you're saying.

Sarah Berry: Yeah. Sissi, I think we need to be pragmatic. In an ideal world, everyone would be able to
have a doctor on call guiding them on everything, a dietician on call guiding them, and a life coach to
motivate them to do their exercise or practice mindfulness. But that's not pragmatic. We don't live like
that, or very few - unless we're an A-list of celebrities who's actually rich who actually have the resources
to do that.

And so, I'm very mindful that dietitians and practicing nutritionists might be quite skeptical about
personalized nutrition apps. And I think, partly they have reason to because there's a lot out there that I
think are claiming things based on just looking at one outcome or exposure. So, looking at only
measuring your glucose responses and saying based on that alone, we will tell you how and what to eat. I
understand the skepticism around that. But I think that we need to be pragmatic and I think for apps such
as the ZOE app, where we measure so many different outcomes, I think that it can actually make a
meaningful difference.

Something else I think it's really important to mention when we talk about personalized nutrition - I think
people don't talk about this whole area of stratified nutrition. As dietitians, you'll have all been doing this
for years as well. So, by conducting personalized nutrition research, people tend to share back with the
companies that are collecting the data and their results. So, you're acting as a citizen scientist. You are
actively sharing from the comfort of your armchair your own data, which enables us to develop more
personalization, but also enables us to build on the science which is really important, and enables us to
simplify some of this down to a more stratified level.

So, if I can use an example of some of the work that we've done with the PREDICT Studies, we've been
looking at pre- and post-menopausal women, for example, and we see that post-menopausal woman, if we
age match them to pre-menopausal women, so we take away the confounding of age, the post-menopausal
women have really high levels of inflammation, they have higher postprandial glucose, higher
postprandial lipids, for example. This is, even though like I said, these are age-matched individuals. So,
this means that we can just in a stratified way, say, okay, you're post-menopausal now and so we
recommend you be a little bit more mindful about the type of carbohydrates you're consuming. And we
can stratify our advice without even someone needing to go and do all of these tests.

So, I think there's a really important byproduct of all the research that goes on as part of this personalized
nutrition evolution as well that we need to embrace.

Sissi Stove Lorentzen: You're actually talking about something very, very important because aren't
people resisting a little bit sharing their personal information? Many people are concerned about their
privacy, what they're sharing, and how well that is secure. Is that also something you think about in this?

Sarah Berry: I can only give you my perspective from the work I've done on PREDICT and ZOE. With
the ZOE app, we have very tight regulations, and very tight privacy policies. We adhere to what's called
GDPR in the UK, so all-around data protection. All of the data that we use for research as all research is
used in its anonymized form.

I haven't found reluctance from individuals in sharing their data, certainly, from PREDICT and from
ZOE. I know for some of the bigger companies such as Apple, I know that there's some resistance or
skepticism or worry from individuals, but it's not something I've come across actually from our users
anyway.

Sissi Stove Lorentzen: How would you advise dieticians today if they want to learn more about
personalized nutrition?

Sarah Berry: I've given lots of talks that are on YouTube. I could always direct them to the talks that I've
given around personalized nutrition. We've also got a website that covers all the research that we've been
doing as part of the PREDICT Studies, which is at joinzoe.com.

We have lots of resources there, around the papers that we've published and around the whole world of
personalized nutrition. And so, I think that's a really good starting point, as well.

Sissi Stove Lorentzen: That's wonderful. So, where do you see yourself and what do you hope to
achieve, let's say, in the next 5 to 10 years?

Sarah Berry: I hope to still be leading the science at ZOE, which is just phenomenal. We're kind of really
pressing the fast forward button, I think, on advances in nutritional research.
I hope in that 5 years to have really mined the data that we already have. We now have data on over
30,000 individuals, really deep phenotypic data. There are so many exciting projects that I want to start. I
want to develop hunger and satiety scores personalized to an individual.

I want to really probe into the how we eat. How important is time-of-day? Meal sequencing? Overlaid
with how much sleep you've had, or how anxious you are so that we can really give people advice, not
just about what they eat, which I think is what we've been doing for the last 50 years or so, but really
thinking about, ‘Okay, you can still eat that but let's think about how you're eating it. Have you just
exercised? What time of day are you eating it? Are you practicing time-restricted eating?’ I think that
that's what really excites me for the next five years.

Sissi Stove Lorentzen: Do you think that there's any area of medicine where medicine meets dietetics,
that it would not be good to do this or to use personalized nutrition?

Sarah Berry: I think that for people with serious medical conditions, or with any kind of medical
diagnosis that interacts with nutrition, then they should certainly seek advice from their physician before
starting any of these personalized nutrition apps.

I think most companies that run personalized nutrition apps are very responsible about that and do advise
people to do that. It has to be adapted for the individual. You don't want a celiac, for example, to follow a
personalized nutrition program that doesn't take into account what you, as a celiac, can and can't eat.

Sissi Stove Lorentzen: Exactly. That was a very good point at the end. But before we close off the
discussion today, can you share with us absolutely the most favorite thing you do? I mean, your projects
seem amazing. You're doing tons of interviews. I just heard all over the place. You're doing all this
exciting new research. But what's really your favorite thing to do? And I might share with you my
favorite thing to do as well?

Sarah Berry: Well, it's you know what, Sissi? My father, when I was growing up, always told me, if you
enjoy your job, you never work a day in your life. And so, I love every minute of the work I do,
particularly since working with ZOE has just been phenomenal. And so, I don't actually work. I do my
hobby all day long, which means I do actually work far too much because I'm too excited. And once my
children are in bed, I'm back at my computer, excitedly looking at the next thing that we're doing at ZOE.
But I think the most exciting thing for me is working between academia and between a tech company and
seeing the agility that working in this way, particularly with a startup, particularly with a tech company
offers research.

And I think that the paradigm shift that we also see in the research, in nutritional research in particular
that I think we should all as researchers be trying to capitalize on and also practicing dietitians in the
novel technologies, the wearable devices, the remote clinical testing that we can do, the home devices – I
think that it excites me the next 5, 10, 20 years that we have this paradigm shift and being able to capture
citizen scientists and capture all of this data. But I think that we need to work in a way such as how we're
working with ZOE in this kind of very agile way as well outside of the typical kind of barriers that
sometimes I would have had in the past as an academic.

That was a very long answer. Sorry.

Sissi Stove Lorentzen: That was wonderful and actually when you started to talk about your father, that
was exactly what I would have probably said very much the same. My father also always said, ‘If your
job can become your hobby, you will have a lifetime of fun.’

I had a business degree before I became a dietitian and I have never looked back. I think the same thing
today - that it's keeping me curious and keeping me reading. My husband is so tired of all the journals I
have in my bed and reading up. But it's just the same thing. It's such an interesting field and I feel so
really lucky to be working both with my patients and having some of the research at the same time.

It was so much fun during this podcast with you. And I can't wait to meet you in person, at one point.
Thank you so much for today!

Sarah Berry: Thank you so much, Sissi. It was lovely to get to chat with you and thank you to EFAD as
well for inviting me to come and join you.

Sissi Stove Lorentzen: Okay, bye!

Sarah Berry: Thanks, bye!