Throughout life we continue to shape our microbiomes.
In fact, I view them as, in adulthood,
as a history of your exposures in life.
Things like pharmaceuticals, diet, infection, sex hormones,
even environmental toxicants can serve as strong
selective pressures on which microbes are present
and what they're producing and therefore
how they're interacting with the host.
And to really reinforce this and add to the complexity,
if we take a point in time not all microbiomes are equal.
This is a study of the gut microbiome
in developing and developed nations in adults in this case.
Here in red and green we have gut microbiomes of Malawian
and Amerindian populations.
In blue we have the U.S. population.
And basically each spot is a profile
of what type of bacteria were in the gut microbiome
of these individuals and how we work through this immense
amount of data that we generate is we ask how similar
is microbiome profile A to all of the other
microbiome profiles in our cohort.
And we calculate a distance.
How similar is it, how close is it
in terms of which microbes are there
and what relative abundance, how much of them are there.
And that's just a visualization
of this distance calculation.
So if we have two spots representing two gut microbiomes
of individuals in these studies that are closely plotted
beside one another, it means that those two gut microbiomes
are very similar to one another.
But what you can starkly see in this,
is the U.S. gut microbiomes are very different
from those of the Marindian and the Malawian population.
And even though the Malawian and the Merindian populations
are on two different continents, their gut microbiomes
in these less developed nations are more like each other
than they are like a U.S. population gut microbiome.
To reinforce what we've done to our microbiomes in the U.S.
this is just looking at the number of types of bacteria
that are detected across these populations.
We have severely reduced the breadth of diversity
and the number of different types of bacteria in the U.S.
population compared to the in less developed nations.
And the really wonderful thing about this study,
is we got indications why this might be happening.
When the study examined with shotgun metagenomics
looking at all the genes and the pathways
and these microbiomes, what really differed
between these populations, what was really striking,
is that the adult population of Amerindian and Malawians
were really enriched for alpha-amylases.
So this is an enzyme that breaks down complex
plant polysaccharides.
So the diet in Malawi and in the Merindian population
is predominantly a plant polysaccharide, a plant-based diet.
In the U.S. population, we see huge enrichment of microbial
metabolic pathways for processing simple sugars.
Found in processed foods, as we all know.
So at least one feature, one thing that we know
is driving these differences in the gut microbiome
across these populations is differences in diet
in what we consume.
And this was reinforced even more recently by Pete Turnbull
who is a faculty member here.
This was a really wonderful diet based study
of 10 individuals.
And what Peter did was he took those individuals
and looked at how a plant-based or an animal-based diet
may actually influence a healthy gut microbiome.
And here we're just showing you the amount of fiber
in their diet of these individuals
before they started the study,
then they got four days of a plant-based diet,
the other participants got four days of an animal-based diet
and as you would expect the fiber content
with the plant-based diet
or the plant polysaccharide content goes up quite high
in an animal-based diet it's very low.
Also, the fat intake is lower in the plant-based diet
compared to the animal-based diet and the protein content
is also dramatically different across these two diets
and he could track that these key dietary component
really shift with the introduction of either
a plant-based diet or an animal-based diet.
What was really striking is that when Peter calculated
again the distance, how similar are the microbiomes
of the individuals after they start their plant-based diet
compared to before they started their plant-based diet,
didn't really see much in the way of change.
Plant-based diet doesn't really perturb the gut microbiome.
However, in comparison, the animal-based diet introduction,
really increased this distance.
And what that tells us is that microbiome is very different
from the microbiome that was there before the introduction
of the plant-based diet.
But it's not just about changing the composition
of the microbiome that matters.
What the study also showed is that you change
the molecular output of the microbiome by changing the diet.
And here we can see that two key short chain fatty-acids
acetate and butyrate were significantly reduced
in the animal-based diet versus the plant-based diet.
And that makes sense because these are the products
of microbial fermentation of plants, of fiber.
And what's really critical is these short chain fatty acids
are crucial energy sources for the cells that line the gut,
they're antiproliferative and they're anti-inflammatory.
And we think they have these activities
because we've co-evolved with these microbes
who traditionally have fermented our plant-based diets
into these small molecules which quench inflammation
and promote kind of health in the system.
And so based on this, I'm sure you're not gonna be surprised
that we're finding an ever-increasing range of diseases
are related to perturbations to the microbiome.
And things like the skin microbiome is perturbed
in dermatological conditions like psoriasis for example.
But what's really exciting is that we are now saying that
conditions like obesity is also linked to
gut microbiome perturbation.
But what's most exciting for me, is that we're finding
that conditions that are very difficult to treat
and that we really don't have a handle on like depression
and autism spectrum disorder are also linked
to perturbations in the gut microbiome.
Suggesting that the gut microbiome
may actually influence remote organs.
And there's a couple of really key seminal studies
that have shown this.
They've shown that perturbations in the gut microbiome
are associated with autism spectrum disorder
and also with cardiovascular disease.
But importantly what these studies have shown,
is that it's microbial metabolites, microbial products
that are responsible for these disorders
and much of this work has been done in mice
with some follow-up work in humans.
So it suggests that the gut is not like Vegas,
what happens in the gut doesn't stay in the gut.
It actually enters the circulation and these small molecules
and perhaps there's some inklings even microbes themselves
may actually translocate to other sites across the body
and change the physiology of the organs there
contributing to the health or disease of those remote organs