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Are you growing microbial cannibals in your gut? Wisdom Wednesdays · Hardiness with Dr Paul Taylor

• 0:05
  Speaker 1: Hey everybody, welcome to another edition of Wisdom Wednesdays. Today
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  Speaker 1: we are going.
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  Speaker 2: To talk about dietary fiber and cannibals. Now, we all
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  Speaker 2: know that dietary fiber is something that keeps us regular.
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  Speaker 2: It helps to feed our gut microbiome. You might even
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  Speaker 2: know that it helps produce short chain fatty acids like
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  Speaker 2: acetate and butyrate and propionate, which are really good for
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  Speaker 2: your heart and your brain. But a really interesting new
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  Speaker 2: paper in the Proceedings of National Academy of Sciences gives
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  Speaker 2: us another reason to.
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  Speaker 1: Care about fiber.
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  Speaker 2: And it turns out, and I've seen similar research before,
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  Speaker 2: but this adds a fair bit of depth, that if
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  Speaker 2: you don't give your gut microbes enough food, as in fiber,
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  Speaker 2: some of them actually turn to cannibals and they start
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  Speaker 2: to eat you instead. And specifically, the bits that they
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  Speaker 2: eat is the mucus layer that.
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  Speaker 1: Protects the wall of your colon itself.
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  Speaker 2: And actually helps to act as an interface between you
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  Speaker 2: and the outside world. And the new bit is that
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  Speaker 2: the researchers have now traced some of those metabolic consequences
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  Speaker 2: of the processes right through into the bloodstream. So first,
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  Speaker 2: let's have a quick tour of your gut wall. So
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  Speaker 2: your colon isn't just a bar tube that has trillions
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  Speaker 2: of bacteria sitting directly against your intestinal walls. the epithelial surface,
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  Speaker 2: that's the epithelial cells, create things like arteries and tissue
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  Speaker 2: linings and things like that. So the epithelial surface of
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  Speaker 2: your colon is actually protected by a layer of mucus.
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  Speaker 2: And they are largely made from proteins called mucins. Now,
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  Speaker 2: think of it as a kind of a slippery defensive
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  Speaker 2: buffer separating your gut microbes from your actual tissue. Now,
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  Speaker 2: your body continually produces this mucus. And under normal conditions,
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  Speaker 2: your microbiome has plenty of dietary material arriving in the colon.
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  Speaker 2: particularly complex carbohydrates and fiber that we humans can't digest ourselves,
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  Speaker 2: something called resistant starch particularly. But the bacteria, they feed
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  Speaker 2: on this stuff and then they produce these really useful
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  Speaker 2: metabolites from the microbes and then everybody gets along famously.
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  Speaker 2: But if you take away the microbial food supply, things
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  Speaker 2: can change. Now, back in 2016, Desai and colleagues, they
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  Speaker 2: published a really cool experiment in the journal SAIL. They
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  Speaker 2: put mice carrying a defined community of human gut bacteria
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  Speaker 2: onto a diet that lacked fermentable fiber. And the bacteria
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  Speaker 2: responded by switching their metabolism towards the carbohydrates contained in
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  Speaker 2: the animal's own mucus, right? And this is the research
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  Speaker 2: I talked about previously. And the mucus barrier progressively thinned,
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  Speaker 2: and then the bacteria moved closer to what's called the
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  Speaker 2: intestinal epithelium, the actual lining of.
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  Speaker 1: The intestinal wall.
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  Speaker 2: And when the animals were subsequently challenged with a pathogen,
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  Speaker 2: they were significantly more susceptible to infection. So that pathogen
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  Speaker 2: could leak through the intestinal wall. And we've known that
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  Speaker 2: for a decade, that at least in mice, the fiber-starved
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  Speaker 2: microbiome can effectively start grazing on the mucus layer and
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  Speaker 2: cause all sorts of issues such as pathogens and other
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  Speaker 2: bits of food to leak into your bloodstream and create
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  Speaker 2: autoimmune conditions.
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  Speaker 1: But the new.
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  Speaker 2: Research is actually pretty clever and they actually followed the atoms.
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  Speaker 2: So a researcher called Abu Salim and colleagues, they wanted
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  Speaker 2: to know exactly where some of the chemicals produced by
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  Speaker 2: the microbiome were coming from. Now, this is harder than
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  Speaker 2: it sounds because once amino acids enter this enormous metabolic
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  Speaker 2: soup of host cells, bacteria, and food, it can be
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  Speaker 2: difficult to tell what came from where. So the researchers
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  Speaker 2: used something called stable isotope tracing. Essentially, they labeled particular
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  Speaker 2: amino acids through an isotope so that they could follow
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  Speaker 2: their carbon atoms through the system.
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  Speaker 1: Pretty clever shit. And it's like putting... a.
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  Speaker 2: Microscope tracking device on the raw ingredients. Now, they were
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  Speaker 2: particularly interested in something called aromatic amino acids, such as
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  Speaker 2: phenylalanine and tyrosine, because gut microbes convert these into a
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  Speaker 2: range of phenolic compounds that are actually good for our health. Now,
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  Speaker 2: some of those compounds appear metabolically benign, and some are
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  Speaker 2: potentially favorable.
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  Speaker 1: Others are a little bit more dodgy.
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  Speaker 2: And two in particular are called phenyl sulfate and P-cresol sulfate.
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  Speaker 1: Now, these are known as uremic toxins.
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  Speaker 2: So you think of urea, that's what you see in
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  Speaker 2: kidney disease. And those uremic toxins, they're well studied in
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  Speaker 2: kidney disease because impaired kidneys have difficulty clearing them from circulation.
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  Speaker 1: That's when you get the buildup of urea. And so the.
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  Speaker 2: Question I ask is, what were, was the microbial tyrosine
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  Speaker 2: that's used to make these compounds actually coming from? And
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  Speaker 2: the answer they found was a significant source was actually
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  Speaker 2: the host animal itself. So the isotope experiment showed that
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  Speaker 2: the tyrosine from host secreted proteins, including the mucins that
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  Speaker 2: I talked about earlier, they entered the gut microbial metabolic pathway.
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  Speaker 2: and contributed to the production of the phenyl sulfate and
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  Speaker 2: the P-chrysosulfate. And the fiber actually changed the process. When
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  Speaker 2: the mice received more fiber, there was less microbial degradation
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  Speaker 2: of the host secreted protein and the concentrations of those
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  Speaker 2: two compounds actually fail. So if you're not really following here,
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  Speaker 2: the upshot was that the fiber that they were eating
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  Speaker 2: wasn't just producing more metabolites. It was actually changing what
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  Speaker 2: the microbes chose to eat and they ate less or
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  Speaker 2: they didn't eat the mucus that was actually part of
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  Speaker 2: the host animal. So in plain language, if you give
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  Speaker 2: your microbes enough fiber, then they don't eat your mucus membrane,
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  Speaker 2: that part of your colon. And so you're not encouraging
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  Speaker 2: them the growth of those cannibalistic microbes. Now, there was
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  Speaker 2: another really interesting part of the experiment that we have
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  Speaker 2: to talk about. So we talked about resistant starch. There's
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  Speaker 2: also resistant protein. So this is protein that doesn't get
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  Speaker 2: properly digested in the small intestine and therefore reaches the
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  Speaker 2: colon where bacteria can actually metabolize its amino acids. Now,
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  Speaker 2: when the researchers provided this digestion-resistant plant protein, its phenylalanine
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  Speaker 2: was used to generate compounds, including something called 3-phenylpropionate, and
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  Speaker 2: compounds contributing to something.
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  Speaker 1: Called hyperate formation. There's lots of big words in this podcast.
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  Speaker 2: But basically, what they found was that the origins of
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  Speaker 2: these metabolites are much more complicated than previously thought. Some
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  Speaker 2: of them are bacterial products. Some can be produced substantially
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  Speaker 2: by our own tissues. And some arise from interactions between
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  Speaker 2: the two. Now, that's really important because it's not the
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  Speaker 2: case of plant protein is good and animal protein is bad.
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  Speaker 1: That's not what this experiment is saying at all.
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  Speaker 2: What it was demonstrating, something more interesting, is that the
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  Speaker 2: substrate or the food parts reaching the colon influences what
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  Speaker 2: the microbiome does with it. Fibre reduces the microbes relianced
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  Speaker 2: on these host secreted proteins, while digestion resistant dietary protein
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  Speaker 2: supplied an alternative pool of amino acids for microbial metabolism.
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  Speaker 2: And intact plant foods help to deliver both, right? So
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  Speaker 2: what this means is that things like beans, lentils, chickpeas, nuts, seeds,
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  Speaker 2: and minimally processed grains They don't just have the protein.
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  Speaker 2: They're actually carrying the protein within this, what we call
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  Speaker 2: the physical food matrix. Alongside it is fiber, resistant starch,
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  Speaker 2: polyphenols and other carbohydrates that reach the lower gut. Now
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  Speaker 2: that's biologically quite different from thinking about nutrients as just
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  Speaker 2: numbers on a food label, right? Now, it is important
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  Speaker 2: to note that this study was done on mice, and
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  Speaker 2: mice have got different metabolic profiles than we actually do.
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  Speaker 2: So it's not an intervention showing that people who eat
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  Speaker 2: X amounts of fiber prevent their gut microbes from consuming
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  Speaker 2: their mucus. We don't yet know the precise fiber intake
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  Speaker 2: that's required to produce the same biochemical effect in humans.
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  Speaker 2: And we shouldn't jump from this elegant mouse study to
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  Speaker 2: claims about preventing disease in people. And the authors are
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  Speaker 2: appropriately cautious about that. However, there is quite a lot
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  Speaker 2: of other supporting evidence that makes the mechanism at least
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  Speaker 2: biologically plausible.
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  Speaker 1: So human and experimental.
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  Speaker 2: Research consistently shows that dietary fiber changes microbial metabolism in
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  Speaker 2: humans and It increases the production of compounds such as
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  Speaker 2: short chain fatty acids, and it interacts with your intestinal
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  Speaker 2: barrier function. And I actually learned that in my master's
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  Speaker 2: in nutrition. 20 years ago, right? And lots of research
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  Speaker 2: described this basic ecological trade-off. When microbiota, accessible carbohydrates, are scarce...
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  Speaker 2: the bacteria capable of consuming the host mucus, they get
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  Speaker 2: an alternative energy source.
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  Speaker 1: So they start to eat your mucus instead.
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  Speaker 2: And human observation data, they're at least directionally consistent. So
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  Speaker 2: what we see is that in people with chronic kidney disease,
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  Speaker 2: higher dietary fiber intake has been associated with lower concentrations
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  Speaker 2: of some of those uremic toxins, while a higher protein
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  Speaker 2: to fiber ratio has been associated with microbial patterns linked
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  Speaker 2: to protein fermentation. Now, it's association, it's not proof, but
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  Speaker 2: it's interesting in light of this new mechanistic work. And
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  Speaker 2: there have even been randomized trials in kidney patients using
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  Speaker 2: resistance starch to try to reduce these gut-derived uremic toxins,
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  Speaker 2: which again suggests that having a bit more fiber can
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  Speaker 2: actually be beneficial.
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  Speaker 1: So what does this all mean practically, right?
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  Speaker 2: Well, you certainly don't need to start measuring phenyl sulfate
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  Speaker 2: or worrying that your microbiome is chewing holes in you
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  Speaker 2: every time you have a low-fiber meal. But the key
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  Speaker 2: is to regularly give your microbes food, right?
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  Speaker 1: And ideally, a variety of it, right?
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  Speaker 2: So this is about having legumes or beans, lentils, chickpeas,
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  Speaker 2: these sorts of things, and peas. They give you the fiber,
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  Speaker 2: the resistant carbohydrates and the plant protein packed together, which
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  Speaker 2: is really, really key. And then it's also about having
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  Speaker 2: minimally processed whole grains such as oats, barley, rice, rather
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  Speaker 2: than these refined grains that we find in supermarkets everywhere.
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  Speaker 2: And human studies suggest that different fibers and whole grains
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  Speaker 2: feed different microbial populations. which is another reason why we
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  Speaker 2: need variety in ours. And nuts and seeds are actually
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  Speaker 2: really important as well. Having different vegetables and a little
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  Speaker 2: bit of fruit. Now, I eat a pretty high protein,
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  Speaker 2: lower carb diet because it's better for me metabolically. But
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  Speaker 2: I do make sure that I include lots of vegetables
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  Speaker 2: and nuts and seeds and a little bit of fruit.
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  Speaker 2: And I do have the occasional potato, but I also
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  Speaker 2: cook and cool potatoes, rice and pasta occasionally to increase
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  Speaker 2: resistance starch. And I'm actually going to do a podcast
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  Speaker 2: on that next week, which will actually follow up on
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  Speaker 2: this one, right? But I think that the takeaway here
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  Speaker 2: is that you can eat a high protein diet and
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  Speaker 2: still look after your gut microbiome. if you're making sure
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  Speaker 2: that you're having a good source of fiber and resistant
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  Speaker 2: starch as well. Which does bring up a question about
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  Speaker 2: carnivore diets. And there's actually some research ongoing right now
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  Speaker 2: around carnivore diets that this thinking was that anybody's on
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  Speaker 2: a carnivore diet is gonna completely destroy their gut microbiome.
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  Speaker 2: And there's a little bit of emerging research that says
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  Speaker 2: that that may not be the case and we may
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  Speaker 2: be a bit more adaptable than we thought. But just
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  Speaker 2: for now, if you don't want to go to that extreme,
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  Speaker 2: making sure that you are accompanying your protein with fiber
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  Speaker 2: and resistant starch is actually a good thing because as
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  Speaker 2: well as getting all of those beneficial short chain fatty
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  Speaker 2: acids that happen when it's fermented, you will ensure that
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  Speaker 2: your mucous membrane isn't eaten by your microbes.
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  Speaker 1: That's it for this week, folks. Catch you next time.
• 13:56
  Speaker 1: Thank you.