A team of researchers from the Snyder Institute for Chronic Diseases at the University of Calgary and the University of Colorado reported that they have discovered factors in the gut microbiome that may improve treatment for patients with gut damage or gastrointestinal disease. Using a mouse model, the researchers’ new findings improved the understanding of the underlying mechanisms that help regulate the enteric nervous system (ENS).

Their findings are published in the journal Microbiome in a paper titled, “Intestinal microbiota shapes gut physiology and regulates enteric neurons and glia.”

“The mechanisms by which the microbiota regulates GI function and the structure of the ENS are incompletely understood,” the researchers wrote. “Using a mouse model of antibiotic (Abx)-induced bacterial depletion, we sought to determine the molecular mechanisms of microbial regulation of intestinal function and the integrity of the ENS.

“We have uncovered microbial factors that help regulate the function and structural integrity of the enteric nervous system,” explained Keith Sharkey, PhD, a professor in the University of Calgary’s Cumming School of Medicine’s department of physiology and pharmacology.

“These and other gastrointestinal diseases with manifested changes in enteric neural control are all hard to treat. Our findings could impact approaches to their treatment,” said Sharkey.

“Be aware, though, that there is a big jump from mice to men. In other words, translating our findings will be important, and our results are only at the starting point of this journey.”

The researchers observed that while microbiome depletion caused a loss of neurons, natural microbiome recovery restored gut function and promoted the growth of new neurons.

“The findings from our work provide clues as to the mechanisms that control ‘plasticity’ or the ability of the gut nervous system to be repaired if it undergoes damage,” said Sharkey.

First author of the study, Fernando Vicentini, a PhD student at the University of Calgary, added, “The most challenging aspect of researching the unknown physiological roles of the intestinal microbiota lies in identifying specific microbial-derived molecules that may affect the host, as there is a myriad of molecules with the potential to do so.”

“Our results suggest a role for the gut microbiota in constantly regulating a variety of GI functions in adulthood, independent of sex,” the researchers wrote. “Depletion of gut bacteria altered GI motility, secretion, and permeability. Moreover, the microbiota is essential for the maintenance of the ENS integrity, likely regulating enteric neuronal survival and promoting neurogenesis. MAMPs, such as LPS, may regulate enteric neuronal survival, while SCFA treatment was found to be associated with both survival and neurogenesis. Thus, we provide additional understanding of host-microbe interactions that contribute to the regulation of GI structure and function and the organization of the ENS.”

Their findings pave the way for the improvement of gastrointestinal disease treatments and gut damage. The researchers are looking forward to exploring other potential microbial factors and their role in the neural control of the gut.

“As our understanding increases regarding the role the gut microbiome plays in gut health, I think we will ultimately have new ways to diagnose and treat gastrointestinal diseases on an individual level,” concluded Sharkey.

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