Monday, December 10, 2012

The American Gut Project

Human Food Project:
We can say with some level of certainty that dietary inputs shape the composition of our gut microbial community. But should we be worried that our gut microbial communities shift around as a function of what we eat and if so, which composition (or ‘state’ as the ecologists like to say), should we be aiming for? That is the million-dollar question.

We know that someone who takes antibiotics can dramatically shift their gut microbes. When this happens, the diversity of the gut microbial ‘ecosystem’ also declines. When diversity declines – among other things – the individual is susceptible to secondary infection. The most talked about secondary infection is by Clostridium difficile, or C. Diff for short. The scorched earth outcome of many broad-spectrum antibiotics is analogous to spraying poison all over your backyard plants and grass and waiting to see what grows back. In the case of your gut ecosystem – just like in your yard – invasive and maybe some not-so-good species (microbes in the case of your gut and some funky weeds in your yard) carve out a niche in the available gut/yard landscape.

From this perspective – gut microbial communities as ecosystems – the ecological principles of diversity and resilience start to help you think about how to fortify your gut against not only invaders that seek to do you harm (also think about E. Coli and others), but also about nurturing a diverse community within your gut that provides what ecologists call ‘ecosystem services.’ In the case of your gut bugs, the services they provide include harvesting energy from otherwise useless nutrients like dietary fiber, pathogen resistance through a number of mechanisms, synthesizing vitamins, assisting in the maintenance of the mucosal barrier that lines in the inside of your intestinal tract – which helps regulate immune response and reduce leaky gut – and the list goes on. In short, when your gut ecosystem shifts as a result of a perturbation – like an insult from an antibiotic, drug, or a shift in your diet maybe – then your equilibrium is out of balance and you tip towards an unstable state which may open you up to disease.

Some interesting studies in mice and humans have shown that a high fat diet can shift your gut microbes which in turn has the knock on effect of low-grade inflammation as measured by circulating levels (in your blood) of a plasma endotoxin known as lipopolysaccharide (LPS). LPS is the primary structural component of the outer membrane of Gram-negative bacteria found in the gut. So how can shifting your gut microbes cause an increase of LPS in your blood? Turns out, the high fat diet reduces (shifts) the levels of Bifidobacterium. These particular bacteria are known to produce short-chain fatty acids (butyrate, propionate and lactate) as a byproduct of fermenting things like dietary fiber. When their numbers go down – as with a high fat diet – the amount of short-chain fatty acids (SCFA) go down as well. These SCFAs are known to improve gut barrier function (think leaky gut) through a number of mechanisms.

So, in this ‘one example,’ if you change your diet (higher fat in this case) you reduce your SCFA production – which is an ecosystem service provided by your microbes – then your gut starts to leak and things that do not belong in your blood start showing up (LPS) and cause low-grade inflammation (the lab coats call it endotoxemia) which has been linked to insulin resistance, type 2 diabetes and obesity (click here for longer discussion on this). It’s interesting to note, that its not the fat per se that causes the Bifidobacterium to shift downward in abundance and thus cause a leaky gut, but the reduction of fermentable substrates. That’s is, you cut off the Bifido’s food supply and thus they slow down the SCFA production – which is prtective. As the famous Rajin Cajun James Carville might say, “It’s the Fiber stupid.”

So what should you eat to improve the diversity and possible resilience of your gut microbiome to reduce the risk to invading pathogens, unnecessary inflammation, leaky gut and so forth? Nobody really knows for sure and the answer is likely different for different age groups and populations. But at a minimum, you want that ecosystem service of SCFAs to keep churning along at high levels – so eat as many plants a week as you can (30-50 is a good number to shoot for – keep track and see how you do) – that is, keep the fiber (non-starch polysacchrides, resistant starch etc) flowing to your colon. And maybe cut back a bit on the easy to digest and hyper-cooked and processed foods – letting your stomach do a little extra-somatic work every now and then. Maybe even open a window every now and then, and for god’s sake, get your hands and food a little dirty. But if we ever hope to get a better handle on what a ‘normal’ or ‘healthy’ gut (or skin, oral etc for that matter) microbiome looks like, we will need to look at less westernized populations who are still undergoing the epidemiological transitions most of us have already undergone.

Getting a larger sample of westernized gut microbiomes is necessary as well and the reason we launched the American Gut project – to crowd source 10,000 gut microbiomes across the diversity that is the American Gut. And also the reason I was trekking in the mountains of northern Namibia. With detailed dietary and lifestyle data and the resulting microbiomes from the American Gut project, we will be able to see patterns not otherwise possible in smaller groups of people. By comparing this data set to more traditional societies – the microbial Noah’s Arks I like to think of them as – we might get a glimpse of how the process of village to urban life shifted and altered our ancient gut microbiome to its current – and very possibly –persistently perturbed state.

More information:
» MSNBC: American Gut Project
» Scientific American: Neurogastroenterology
» New York Times: Microbes Defend and Define Us
» NIH: The Healthy Human Microbiome

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