Gut muscle contraction by the nerve cells is regulated by microbiome

Gut muscle contraction by the nerve cells is regulated by microbiome

Micro-organisms in the gut support healthy digestion by helping nerve cells within the intestine to regulate the contraction and relaxation of the muscle wall of the colon, according to new research.

The study, published in Nature, identified how the contraction and relaxation of muscles in the colon, which is regulated by nerve cells and is needed to push food along, is influenced by the bacteria resident in our gut. When such microbes are present, a specific gene called Ahr is activated in intestinal nerves, resulting in healthy contraction and relaxation of the colon (peristalsis). This relationship can be disrupted in cases of intestinal disorders, like irritable bowel syndrome (IBS).

"There is a clear link between the presence of microbes in the colon and the speed at which food moves through the system. If this relationship goes off-kilter it could cause considerable harm," says the lead author.

A healthy gut contains trillions of microorganisms which help the digestion of food and promote the fitness of gut tissues, such as the epithelial lining of the lumen and the vast collection of immune and nerve cells within the gut wall. The levels and types of microorganisms in the gut vary from person to person and are affected by diet and commonly used drugs, such as antibiotics, which often result in abnormal gut contractions. The work described in this paper helps us understand how nerve cells sense the microbes in the gut and how they could coordinate their function with other gut tissues.

The authors demonstrate that the intrinsic neural networks of the colon exhibit unique transcriptional profiles that are controlled by the combined effects of host genetic programs and microbial colonization. Microbiota-induced expression of AHR in neurons of the distal gastrointestinal tract enables these neurons to respond to the luminal environment and to induce expression of neuron-specific effector mechanisms.

Neuron-specific deletion of Ahr, or constitutive overexpression of its negative feedback regulator CYP1A1, results in reduced peristaltic activity of the colon, similar to that observed in microbiota-depleted mice. Also, expression of Ahr in the enteric neurons of mice treated with antibiotics partially restores intestinal motility.

"Disturbances of intestinal motility are extremely common and cause a lot of suffering in patients after surgical operations or in conditions such as irritable bowel syndrome. This work provides a foundation to unravel why patients that are colonised with different groups of microbes are susceptible to these intestinal problems", explains the author.

"While it's been well-documented that the micro-organisms in our gut influence the function of many organs in our body, including the brain, there's less understanding about the role they play in maintaining the healthy functioning of the millions of nerve cells within digestive system itself. The work we describe here shows that AhR, a molecule which is very important for the function of immune and epithelial cells in the gut, is also used by intestinal nerve cells to sense the presence of microbes and regulate peristalsis, and in doing so, promote healthy digestion," says the co-lead author and group.

"In the future, the use of microbial products that change the activity of AhR in nerve cells could help us alleviate the consequences of abnormal gut peristalsis that is often associated with gastrointestinal diseases," continues the author.