Of Mice & Microbiomes: Evolving Gut Bacteria in Mammals

The microbiome, the microbial community that lives in our gut, has been a tremendously active research area over the last few years. From its sheer presence to its role in health, immunity and behaviour, the microbiome has caught the imagination of scientists and science communicators alike. Of course, humans aren't the only animals to harbour a microbiome, and recent research has uncovered some intriguing patterns in our relatives' microbiomes.

A 2005 study showed that there is considerable diversity in the composition of the human intestinal microbiome. Individuals have distinct microbial communities living inside them, determined by a variety of factors including their diet, where they live, and their genetics. Later work looking at the population level found that human microbiomes cluster into three groups, called enterotypes. Of all the factors influencing the make-up of the microbiome, the one separating the enterotypes seems to be diet; the effect of age, sex, and geography are secondary to this principal division. People who ate more animal fat and protein had a microbiome of one enterotype, while those with more carbohydrates had another enterotype. Despite its importance, a ten-day switch in diet wasn't enough to change enterotypes in humans, leading to the idea that enterotypes are shaped by long-term dietary habits. In 2012, researchers discovered that the chimpanzee microbiome clusters into enterotypes similar to those found in the human population, a tantalizing hint of the antiquity and importance of these communities and their interactions with their hosts.

Most recently, an international team of researchers investigated the microbiome of wild mice. A study last year catalogued the microbiome of lab mice and found two enterotypes, but that might not reflect their situation in the wild. After all, lab mice are fed a controlled, standard diet and are sometimes even inoculated with specific bacterial strains. To get an idea of the situation in wild mice, the team analyzed fecal samples from 80 mice collected from eight locations around Western Europe. They found that the microbial communities in wild mice clustered into two well-supported enterotypes, which they labeled E1 and E2. Not only do these match the enterotypes found in lab mice, but they're also similar to two of the three clusters found in chimps and humans. While mice lack the third enterotype, its characteristic bacteria group is closely related to a signature taxon in E2. So it turns out that mice, humans, and chimps all have a diverse microbial community in their intestines which cluster into similar groups.

The team also found strong evidence that enterotypes are determined by diet in mice, as they are in humans. A metagenomic analysis showed that the E1 enterotype has more genes related to protein metabolism, while E2 has a higher proportion of carbohydrate metabolism genes. Using stable isotope probing, the researchers investigated the dietary history of the mice and found that it correlated with their enterotype. And clearly demonstrating the link, wild-caught mice with an E1 microbiome consistently shifted to E2 within a week of being transferred to the lab, concomitant with the dietary shift in their new home. Why did the mice shift enterotypes after a dietary switch when humans didn't? The researchers suggest that it might be because they have a higher metabolic rate than we do. But that still leaves another question: if wild mice all switched to an E2 enterotype after being transferred to the lab, why did an earlier study find to enterotypes — E1 and E2 — in lab mice? The answer to that is less clear. It may involve changes in the metabolic and immune systems of (inbred) lab mice, and it may also be that the E1 enterotype re-emerges over time in the lab mice. As always, the only way to find out is through further research.

To my mind, the most interesting aspect of this research is its evolutionary implications. Why do humans, chimps, and mice have similar enterotypes? And what are we to make of the shared link to diet? One intriguing possibility is that similar constraints and selective forces have shaped convergent microbial communities in the different groups of mammals. After all, all three species eat a wide range of foods and have roughly similar guts, so these microbial communities might just be best-suited to those circumstances. But that would still mean that the existence of enterotypes — that is, structured variation in the microbiome — predates the diversification of the major mammalian orders 100 million years ago. Whatever their precise composition, enterotypes may well be shared traits across the range of mammalian microbiomes, offering us a glimpse into the interminable interplay between the evolution of individuals and ecosystems.

Refs
Wang J, et al. Dietary history contributes to enterotype-like clustering and functional metagenomic content in the intestinal microbiome of wild mice. Proc Natl Acad Sci USA 111:E2703–E2710. (2014) doi:10.1073/pnas.1402342111
Moeller, A and Ochman, H. Microbiomes are true to type. Proc Natl Acad Sci USA 111:9372–9373. (2014) doi:10.1073/pnas.1408654111