Biomedicine

Q&A: The Future of Probiotics

New technologies will shed light on how beneficial bacteria might help our health.

Probiotics–the ingestion of live microbes to boost health–might conjure images of aging hippies in health-food stores buying esoteric brands of yogurt. But in fact an emerging body of scientific data is showing how probiotic treatments can beneficially impact both the millions of microbes within our gut and the health of their human host. Earlier this week, a conference convened by the National Institutes of Health surveyed the state of this growing area of medicine. A mix of immunologists, microbiologists, nutritionists, clinicians, and even members of the Department of Defense descended on a hotel in Rockville, MD, to hash out the implications of the latest clinical trials in probiotics.

Jeff Gordon

Studies of animals raised in sterile environments have shown that microbes in the gut play a vital role in both development of the immune system and in digestion itself. (See “Our Microbial Menagerie.”) People have been trying to shape these communities for the better by eating fermented foods full of bacteria, such as yogurt, for hundreds of years. But it’s only recently that probiotics have been tested more rigorously for a number of health conditions, including allergy, Crohn’s disease, and diarrhea. However, because these studies have used different formulations and been limited in size, they have yielded mixed results. Both scientists and physicians hope that better characterization and understanding of the microbial communities that live within us could help shape and interpret these studies, eventually bringing forth a new era in microbial medicine.

One of the major limitations in studying the impact of probiotics is the inability to grow most gastrointestinal microbes in the lab. But new technologies that use DNA analysis to study the microbes of the gut without culturing them–an approach known as metagenomics–are offering researchers an alternative approach. (See “Metagenomics Defined.”) A growing number of studies published in the past two years reveal a stunning diversity of our microbial inhabitants: people harbor 100 to 1,000 different types of bacteria in their guts, and additional varieties are uncovered with every new person studied. Projects are now under way to examine how different factors, including disease and probiotic treatments, shape these communities.

Jeff Gordon, a microbiologist at Washington University in St. Louis and the organizer of the conference, has been a leader in metagenomic studies of the human gut. He spoke with Technology Review about how these new technologies might shape the microbial medicine cabinet of the future.

TR: Are we on the verge of a revolution in probiotics?

JG: I’d describe it as rapid evolution. Probiotics have been around for years, and the questions we’re asking–such as what shapes microbial communities–are very old questions that have been asked since the birth of microbiology. What has changed is the types of tools and experimental systems we have to study them. We have new sequencing technologies and metagenomics, gnotobiotic [microbe-free] animals, transgenic mice, and sophisticated methods of metabolic profiling.

TR: How are these technologies changing the way we think about probiotics?

JG: If we’re going to try to intentionally alter the gut microbial community, we need to better understand it.

I think the confluence of metagenomic and other factors is allowing us to start to address the question, what is the mechanism of action? How general are the effects? What effects do they have on the gut microbial ecology and on the host? Do interpersonal differences in gut microbial ecology determine probiotics’ effectiveness?

We’re initially describing what microbes are present on an organismal and gene level, and then looking at the function of these communities. This will provide an unprecedented opportunity to determine the circumstances under which a person should consume live microbes.

TR: How will this affect development of probiotics as products? Most current studies–and probiotic-labeled foods–contain only one or a few strains of bacteria.

JG: We have to think of microbes as part of a community with properties that result from that community. The types of compounds a community will make might be affected by the host, so types of products might emerge that may only be apparent when you study the whole community.

TR: Several studies have examined probiotic treatment in pregnant women and newborns, and preliminary evidence suggests that this might have a long-term impact on reducing some allergies.

JG: There may be a critical period in development in determining an individual’s microbial profile. We need to start thinking about what forces shape the community assembly. There may be a dynamic interplay between microbes and diet that could have a long-term impact on the host.

TR: Your lab has previously shown that obese and lean people have differences in their microbial populations that impact how efficiently foods are digested. What are you working on now?

JG: My lab is trying to place the human gut microbiome in the context of evolution. How was it shaped by evolution? Is it changing with our rapidly changing lifestyle? We’re just completing a large global study of the mammalian gut, including species of nonhuman primates, carnivores, herbivores, and omnivores.

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