Together We Stand, Divided We Fall: How Microbes Cooperate in the Human Gut

Bioreactors used to culture gut microbes in the Allen-Vercoe lab (photo by S. Rosiana)

The gut microbiota has long been a source of fascination to microbiologists, including which microbes dwell there, and how they keep us healthy.  But it is only in the last decade or so that scientists have been able to truly delve into the complex microbial ecology of the human gut, thanks in part to the invention of bioreactors that can mimic the conditions found in the intestine.  These game-changing machines were developed by Prof. Emma Allen-Vercoe, Department of Molecular and Cellular Biology, and today they continue to play an essential role in her lab’s research.  Kaitlyn Oliphant, a recent PhD graduate from the Allen-Vercoe laboratory, took advantage of her lab’s “robogut” technology to explore how different species of gut microbes interact in a healthy individual.

“Therapeutics that help restore an altered microbial community in the gut have a lot of potential to treat gastrointestinal disorders and other conditions,” says Oliphant. “But in order to design effective therapeutics, we have to first understand the ecology of a healthy gut environment, including how different microbes interact with each other.”

Oliphant’s first step was to obtain a fecal sample from a healthy individual.  But what exactly does a healthy gut microbiota look like?  The short answer, says Oliphant, is that nobody knows yet. 

“We use general trends in an attempt to describe a healthy gut microbiota. For this study, a fecal donor was deemed healthy not based on gut microbe composition, but if they were generally healthy, disease free, hadn’t had antibiotics for a given period of time, and other certain criteria.”

After identifying such a donor, Oliphant isolated the different species of microbes contained in the sample.  She then recombined the individual strains in a bioreactor to recreate a healthy gut microbial community.

An identical community of microbes was formed in another bioreactor but with a twist: each species of microbe was obtained from a fecal sample from a different person, rather than all coming from one individual.

“If all the species come from one person, it should mean they are able to work together and coexist,” explains Oliphant.  But if the species come from different people, they may not cooperate in the same way.

Oliphant cultured the two communities under identical conditions in media that replicated conditions in the human gut.  

When the microbial communities reached a “steady state” after several days, the researchers discovered that overall the species composition was similar between the communities. However, the chemical by-products resulting from microbial activity in the bioreactor were a little different. In the microbial community constructed from multiple fecal donors, the microbes appeared to be degrading primarily protein instead of carbohydrates.

This preferential breakdown of protein has important consequences.  Digesting carbohydrates provides more energy than proteins, and in an actual human gut, the by-products of carbohydrate degradation are the preferred energy source for the epithelial cells lining the gut. Protein degradation, on the other hand, produces by-products such as phenols, biogenic amines, and ammonia, which can potentially be proinflammatory or toxic. This doesn’t mean consuming protein is bad, but it may not be ideal as a lone energy source.

It is thought that the difference between the two communities may be because gut microbes rely on cooperation for carbohydrate degradation, and microbes obtained from different people may simply not cooperate as well. When microbes grow together over an extended time period, they “co-adapt” to their environment and may be able to work together to produce different enzymes to break down energy sources efficiently. When microbes do not have a history of growing together, they don’t cooperate as effectively and resort to degrading proteins.

It is clear that for both gut microbiota and the person housing them, cooperation is important – and future therapeutics may need to be based on co-adapted, cooperative microbes for the best results.

Oliphant is now pursuing a post-doc at the University of Chicago. She is still studying the gut microbiota using bioreactors, but this time with a greater focus on the clinical aspect of her research.

“My hope is that this research will provide new insights into the gut and help with future development of therapeutics for those struggling with GI disorders.”

Valeria Parreira and Kyla Cochrane, Department of Molecular and Cellular Biology, also contributed to the study.  This research was funded by the Natural Sciences and Engineering Research Council and a National Institutes of Health R01 grant.

Read the full study in the ISME Journal. 

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