Weekend Review: All about the Gut - Diet and Immunity

As Boston gets buried under a layer of snow (wooo! blizzard!), the the Weekend Review makes a return with one of my favorite topics: gut microbes.

ResearchBlogging.orgThe fields of immunology, microbiology, nutrition and metabolism are rapidly converging. Here we expand on a diet-microbiota model as the basis for the greater incidence of asthma and autoimmunity in developed countries.

Two important advances in the fields of immunology and gut microbiology have emerged in recent years. First, it has been clearly demonstrated that diet has a considerable effect on the composition of the gut microbiota. Different human populations can have vastly different intestinal microbiomes, and changes in diet lead to changes in microbiota composition. Second, findings from many laboratories have shown that the composition and products of the gut microbiota have unexpected effects on immune and inflammatory responses.

There are bugs in your gut. Lots of 'em. They've been ignored for a long time, but it's becoming more and more clear that they have a profound influence on our physiology. In fact:

The gut microbiota can be considered an extension of the self and, together with the genetic makeup, determines the physiology of an organism.

Microbes are a fact of life. They're on every surface of your body that's exposed to the outside world, and they've been with you since you were born. But the largest numbers, and the largest diversity of bacteria are in your gut. That we are host to this legion has been known since the dawn of microbiology (von Leeuwenhoek found microbes in his saliva), but for most of that time, commensal (literally: eating at the same table) microbes were off-limits to researchers - many are incredibly difficult to culture outside of their native environment. But in the last decade, new sequencing technologies have enabled us to begin unlocking the secrets of our tiny passengers.

Whereas microbes in the gut were once considered only harmful or pathogenic, it is now clear that commensal bacteria accomplish many beneficial functions, such as vitamin synthesis, the digestion of dietary fiber and the regulation of inflammatory responses. Microbes and vertebrates have evolved together over the millennia, so normal functioning of the digestive and immune systems depends on the presence of nonpathogenic 'beneficial' bacteria (symbionts)

As a quick recap, gut bacteria have been shown to play an important role in obesity, diabetes, inflammatory bowel disease, allergies, rheumatoid arthritis, and a host of other human ailments. And fecal transplants (yes, that's exactly what it sounds like) from healthy donors can restore an unhealthy bacterial composition and are becoming increasingly common as a treatment for chronic intestinal inflammation. The first three I mentioned might make sense - they're all based on the gut and metabolism, but an emerging role for microbes training the immune system has linked these bugs to just about everything linked to the immune system - which is to say: everything. But first, some caveats:

Many of the studies I mentioned above are largely based on mouse models of disease, or on large-scale sequencing analysis and correlational studies. For instance, a study published in Nature in 2006 showed that obese people and mice have different compositions of 2 major families of bacteria (firmicutes vs bacteroides), and that this composition changes with weight gain and weight loss. Other studies have shown that transplanting microbes from obese mice to normal mice can make normal mice gain weight. These results, while intriguing, don't really get at the mechanism.

Still, more recent studies are starting to break ground on specific species or groups of species, and how these might be manipulated. The authors of this article argue that the western diet, which is high in sugar and fat and low in fiber, changes the microbial composition of our guts and might contribute to increased incidence of allergies, asthma and autoimmunity.

If diet affects the composition of the microbiota, and the microbiota regulates immune and inflammatory responses, then diet should have easily quantifiable effects on the immune response. Although the results of studies in this area are highly promising, most of the evidence so far has been indirect or has been derived from studies with limited numbers of trial subjects[...]

If the microbiota does have a substantial bearing on immune responses, as the preliminary reports discussed above would suggest, then this opens up new avenues for therapy. Probiotics (live microorganisms thought to be healthy for the host) have been tested in many clinical trials, with some notable successes, although few large-scale trials of humans with inflammatory disease have been undertaken. It may be true that clinical trials with probiotics will also need to incorporate dietary considerations, because probiotics require fiber for their metabolism

This field is in its infancy, and there are many variables that could confound any findings. Besides that, there are many technical hurdles that prevent direct manipulation and controled experimentation. But we're getting better. And the wealth of potential payoffs make the endeavor well worth it.

The recent flurry of research articles on diet and its effects on gut microbiota, together with the new findings on the regulation of immune responses by microbiota, opens up an entirely new approach to the understanding and treatment of human inflammatory disease[...] There may be numerous molecules produced by gut microbes, or dietary molecules themselves, that affect immune responses. Rather than developing new anti-inflammatory drugs, it might be more cost-effective to devote more effort to new approaches

Maslowski, K., & Mackay, C. (2011). Diet, gut microbiota and immune responses Nature Immunology, 12 (1), 5-9 DOI: 10.1038/ni0111-5