The human gut is home to microorganisms that outnumber our cells by a factor of 10 to 1. Now, discoveries by scientists have redefined how the so-called gut microbiome operates and how our bodies coexist with some of the 100 trillion bacteria that make it up.

The new findings appear in the journal Science and could lead to new therapies for inflammatory bowel disease and people who've had portions of their bowels removed due to conditions like colon cancer and ulcerative colitis. They also help explain why the use of antibiotics can create a multitude of problems in the digestive system.

Using research models, a team of scientists who found the microbiome controls the creation of a sticky layer of special forms of sugar-enriched mucus that encapsulates and travels with fecal matter.

The authors found that colon mucus consists of two distinct O-glycosylated entities of Muc2: a major form produced by the proximal colon, which encapsulates the fecal material including the microbiota, and a minor form derived from the distal colon, which adheres to the major form. The microbiota directs its own encapsulation by inducing Muc2 production from proximal colon goblet cells. In turn, O-glycans on proximal colon–derived Muc2 modulate the structure and function of the microbiota as well as transcription in the colon mucosa. 

The mucus -- which the researchers showed not to be static as previously thought -- acts as a barrier between bacteria in feces and the thousands of immune cells in the colon. Without the mucus, the whole system gets thrown out of balance.

"The colon is not just a digestive organ, but an immune organ," said the senior author. "Our microbiome begins to develop at the moment of birth and evolves throughout our lives. It's essential for the growth and maturation of the acquired immune system in our body. When it's not well developed or cared for, it doesn't operate as it should, which can lead to diseases."

The overall health of the gut microbiome is dependent on the presence of its mucus. And although mucus production can be interrupted, researchers showed that it can be restored.

In the study, the researchers found that the fecal matter of mice treated with a broad-spectrum antibiotic had no trace of the mucus coating. And when mice without this protective barrier received a transplant of fecal matter with microbiome, their mucus production jump-started.

This may have significant treatment implications for patients whose microbiome is out of balance, the author explained.

"Whether because of antibiotics interrupting mucus production or a total colon removal due to ulcerative colitis, painful inflammation can result," said the author. "Now that we better understand the role and origin of this mucus, we will study how we can supplement it or restore its production."

The findings may open the door to alternatives to colonoscopies for monitoring conditions like inflammatory bowel disease. "Rather than repeated invasive procedures to track the progression of IBD, we may be able to measure the presence of the mucus in a fecal sample and assess a patient's gut health," the senior author said.

https://omrf.org/2020/10/22/omrf-discoveries-reshape-understanding-of-gut-microbiome/

https://science.sciencemag.org/content/370/6515/467