the fermented food thing was a huge hit, such a huge hit. there was a subset of people getting a
little higher inflammation from the fiber. dietary manipulation to optimize the microbiome to lower
inflammation. food intolerances are on the rise and a lot of people report difficulties with
fiber-rich foods. I recently got to discuss this with Dr Christopher Gardner. his lab at Stanford
has been studying human nutrition for decades and they recently published a groundbreaking study
looking at the effect of fiber and fermented foods on health. we also covered a number of
possible solutions and strategies for people who have trouble digesting fiber-rich foods. here's
our conversation. there was a study that you published with the Sonnenburg lab which touched
on this individual diversity and the intolerances, which is a big topic now, precisely because some
people don't do well on diets that are supposed to be great, and so you guys published this seminal
paper on fiber intolerance, can you briefly go over what you found and kind of the takeaways?
yeah, this one was super fun because when we got into it the sonnenburgs had been working with mice
for decades and everything they did to them, drugs and surgeries and gnotobiotic germ-free mice,
diet was the lever that was affecting the microbiome in a positive way, and they were
terrified of humans because they know humans cancel and reschedule and they're rude on the
phone sometimes, and my group hates poop because it's icky and it smells bad, and so like neither
of us wanted to do the other thing but at a conference one time we spoke back to back and just
like star-crossed lovers, after our talks we said, ah I want to work with you, no, I want to work
with you, and it's like two pieces of the amulet, like you do the poop and you recruit the people,
and in the first big study that we did with them that just got published in Cell last year,
we were talking about, so let's do prebiotics and probiotics, let's do fiber-rich foods and
fermented foods, and it was kind of funny because Justin was humoring me, he said, you know, we've
been doing fermented food stuff with the mice and not much was happening, and he's pretty sure it
was all about fiber and he was just gonna humor me because he was happy we were going to recruit the
humans. and we got 18 people to eat as much fiber as humanly possible and 18 people to eat as many
servings of fermented food as humanly possible. so let's stop again here and go back to sort of that
dietfits idea, how much fiber? how much fermented food? what is high? and so we took people,
you got excluded if you were eating a lot of fiber because there wouldn't be as much
room for improvement, so you were supposed to be getting no more than 20 grams a day
and we were going to try to double it to 40 or higher if you could go higher, and for the
fermented food group, almost no one was eating fermented food in the Bay Area so that was easy,
and we sat around the table thinking how, you know, the bigger of a perturbation you make,
the more likely you are to see a response, so a serving or 2 a day, that seems trivial. three or
four? what about six? what about six servings? and oh my God, that sounds ambitious, except...
think about sauerkraut and kimchi which are two of the key foods that we were asking them to eat,
half a cup is like 50 calories or less, so we actually put together a whole bunch of different
combinations of six servings of fermented food, and the average caloric intake was 300 calories.
six servings a day, if you're eating an 1800 calorie diet, that's a sixth of your calories,
it's not like half your day or all your food. it's not six meals,
it's six servings. and the fermented food people did get up to five or six servings a day and
maintained it for six weeks. the fiber folk got up to 40 or more grams of fiber a day and maintained
it, and I'll go off of the fiber because that's... actually let me do the fermented first because
that was really easy, pretty much across the board their microbial diversity increased,
fascinatingly it wasn't just the bugs in the foods they were eating, we did a whole little
thing on the side to show that by changing the milieu of the environment in the colon,
new species appeared that maybe were there hanging out and were just at subdetectable levels. anyway,
the diversity increased, and we looked at inflammatory markers and 20 different inflammatory
markers went down and decreased, so the fermented food thing was a huge hit, such a huge hit that
when I handed him the data Justin called me up and said, are you sure you didn't mismatch the
coding? you said, is that the fermented? because I think you gave me the fiber instead of... no,
no, I double- checked, that was fermented, so we went back to the fiber and looked,
nothing was really going on on average. and I thought, ah! this is... wow this is pretty
backwards because I really thought fiber was going to do it and fermented wasn't.
let's look at it a little closer, at the fiber, and I had this amazing postdoc, Hannah Wastyk,
and another one Gabriela Fragiadakis who's now at UCSF, and I think Hannah started her own business,
they looked sort of at what was the baseline diversity of the microbiome,
and they also looked in the stool samples to see what kind of fiber was coming out
the other end that wasn't chewed up as fuel by the bacteria, and so what they
found was there was a subset of people who were so getting a little higher inflammation
from the fiber, and the ones who did that were the ones who had low microbial diversity and
were churning out lots of fiber in their stool, as if to say, oh man, firehose of fiber coming down
the pipes, whoa whoa, slow that down, I don't know the capacity to handle this, just send it through,
send it, oh my God, inflammation, right? whereas another group that had higher microbial diversity
handled that better, they didn't have as much fiber coming out in their stool because they
were chewing it up for fuel and they lowered their inflammation, but when you put the two together
it canceled. hmm the average. it was like, looked like nothing was going on, so the sonnenburgs did
a beautiful job sort of framing this as, if you want something foundational, people don't eat a
lot of fermented food and we saw very consistent benefits across the 18 people who did this,
across the 18 people who did fiber, it appeared we had nothing, but this looks like a level of
personalization, with a depleted baseline microbiome, they had difficulty with a high
fiber diet, and so maybe someone like that needs to ramp up much slower or maybe never
get there or maybe have fermented food first and increase their diversity, and that's actually one
of the designs we have right now, so we have one group doing fiber, one fermented food, one both
and one neither. maybe if you're doing them both, if you could increase your diversity with the
fermented food and then have a greater capacity to handle the fiber that's coming. so these are
answers we don't have but a tantalizingly fun study to do and see the responses of these
two different groups around, if you don't mind my ending this particular conversation on this note,
inflammation, which is a hot topic but we have crappy metrics. hundreds of inflammatory markers.
is it CRP, is it il-6, is it sicam1, is it mCP, is it... oh my God there's,
I have this huge list of inflammatory markers that I get back from the human immune Monitoring Center
and I said, can you just give me a number, can you tell me like, Gil's inflammatory status is 52 and
mine is 35 and I should aspire to be Gil and to do that... no, I have hundreds of inflammatory
markers with no cutoffs for clinical high or low or normal like you would get with a lipid
or a blood pressure or a glucose and so that's a very fun field. I´m thinking of this trifecta of
dietary manipulation to optimize the microbiome to lower inflammation. the diet´s confusing,
there's hundreds of microbes in your colon and there are hundreds of inflammatory tests.
we need better metrics for inflammation. yeah, not to mention the location aspect,
because we're measuring inflammation markers in the blood, in the serum, but there could be
localized inflammation in different regions... the ramping up makes sense, the ramping up of fiber,
I think that's pretty standard in gastroenterology when people have these intolerances, it's like a
slow incremental increase of specific types of food and if they're introduced too suddenly,
yeah people oftentimes can't handle it which a lot of times leads to misunderstandings,
particularly on the internet, that people just do these drastic changes and they don't do well
on it and they conclude, oh these foods are bad for humans then. right? well, not necessarily...
if I go to the gym and I've been sitting on my couch for 10 years and I just put on the
maximum weights and I injure myself... thank you! thank you! oh, lifting weights is no good for me,
I tried and I'm in horrific pain, clearly resistance training is bad for you. no, we have
a fantastic gastroenterologist, Sean Spencer, who sees patients and is just doing a world of good
playing around with them and slowly increasing these folks, and he's got people with IBD and IBS
and food intolerances and he's got people coming in, all they eat is chicken and rice, they just,
chicken and rice don't cause any kind of flares or disruption in their GI tract and they're fine
but they're going crazy, they want something more than chicken and rice, and so he's helping
them eat sort of a more fiber-rich plant-based diet by introducing these things and varying it
clinically, and hopefully he's going to get some grants funded to follow up on those ideas [Music]