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

Comments

  1. #1 red rabbit
    December 27, 2010

    It’s a fascinating thought…. there is potential valid mechanism. I just hope the woomeisters don’t get hold of this before it’s validated because I really don’t want my patients coming to me demanding a poo transplant.

  2. #2 seattle chiropractor
    December 27, 2010

    If we can just get people to understand that they need to stop killing the good gut bugs with antibiotics, everyone will be a lot healthier.

  3. #3 anthrosciguy
    December 27, 2010

    red rabbit, no doubt coffee enemas will become a thing of the past, replaced by…

  4. #4 Kevin
    December 27, 2010

    @ red rabbit – It’s the future man, embrace it :-P. But seriously, you make a good point. Hopefully our knowledge about the mechanism will advance to the stage where we actually have evidence-based interventions before the kooks start coming out of the woodworks.

    @ seattle – I definitely agree that antibiotics are over prescribed (often because patients are demanding antibiotics for a cold or flu), but there are times when antibiotics really are essential. It’s unfortunate that most antibiotics are so non-specific, but hopefully we’ll start to learn how to repopulate the good bugs.

  5. #5 Jessica
    December 27, 2010

    There are already a few kooks in the woodwork. There are people who think that fecal transplants will ‘cure’ autism by fixing the (non-existent) gut issues that ’cause’ it. I already know my answer to the ‘magic pill’ question is a firm no, but it becomes a HELL NO when the magic pill is actually shit.

  6. #6 Stefanie
    December 27, 2010

    Kevin–I am PhD student at Johns Hopkins in Political Science. I am using metaphors of immunology and research like yours and the posts you blog about on We, Beasties to attempt to think about different ways of imagining the self and its relation global community. I would very much like to trade thoughts with you about my dissertation and the research you do. Really fascinating and full of potential for so many things! I post occasionally on a blog called “An Embodied World”. I have a description of my project there.
    http://anembodiedworld.blogspot.com/

  7. #7 Mike Olson
    December 27, 2010

    1. Regarding that transplant: how do you perform the cross match?
    2. Exactly how would you know if the transplant took, or there was donor rejection?
    3. For all I’m hearing(reading) fecal transplant, it all begs a question, which is of course, why not just culture the bacteria, place it in a time release media and dispense it as a capsule?
    4. Does this change the meaning of, “I ain’t takin’ any shit from anybody?”
    5. Are you kiddin’ me? Fecal transplant? How do ya find shit that is pure in one species of bacteria, but low in some other species that could cause more/different problems? My point goes back to: why transplant shit? If you culture intestinal bacteria you can choose one specific species and not concern yourself with a “shotgun” approach.
    6. I’m really serious here…someone please tell me why they would transplant the whole enchilada…so to speak…

  8. #8 Kevin
    December 28, 2010

    @ Mike –

    1. Usually they take a family member or spouse – someone that is likely to share your gut flora
    2. Rejection isn’t really an issue the way it is for tissue transplants. Your immune system usually knows to ignore gut flora. And you know it took if the patient gets better.
    3. We know so little about the gut environment, even if we could culture just the bugs we want (and we really can’t culture the vast majority), we wouldn’t even know which ones to culture.
    4. Yes, but only if you have chronic C. dificile infection or IBD.
    5. You don’t – the whole point is to transfer the entire healthy ecosystem (yes, your bowels are an ecosystem). If we knew the one species of bacteria that was important, I’m sure we would figure out how to culture it. But there’s a huge interlocking web of interactions that we’re only just starting to understand. This is a hugely empirical treatment at this point – we know it works, but we really don’t understand how it works.
    6. A spicy enchilada will almost certainly affect the balance of microbes in your gut.

  9. #9 Mike Olson
    December 28, 2010

    RE: transplant issues, I’m aware fecal material is not tissue. I recently read a very good book which pretty much described how we are innoculated with a variety of bacteria beginning at birth and of course through life. It also described how our entire system, not just gastrointestinal was an eco-system, as well as the effects you describe here, such as creating different sorts of “rxns” that were essentially thought to be unrelated. Frankly, the name escapes me at the moment…but, my point is I was being somewhat facetious. However, to be fair, you did answer my genuine question about why it couldn’t simply be cultured and purified. Thanx!

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