Microbiome: Caltech team discover key to healthy bacteria gut colonization

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07 May 2018 --- A Caltech study has found that a beneficial gut bacteria – Bacterioides fragilis (B. fragilis) – harnesses the body’s immune response so that it can thrive safely in the gut – enhancing human health by boosting our microbiome. These findings shed light on the question; how do mammals maintain harmonious relationships with the beneficial bacteria in the gut when our immune system has evolved to repel microbes? 

“Studies by other labs have shown that most people carry the same strain of B. fragilis throughout their lives. We wanted to understand at a molecular level how these bacteria are able to colonize the gut in a stable, long-term way,” says Gregory Donaldson, graduate student and lead author.

“It is surprising to find that an immune response actually helps beneficial bacteria to thrive, which in turn helps the host thrive,” adds Donaldson.

The research, published in Science, examined the bacteria B. fragilis which has been found to protect mice from certain inflammatory and neurological disorders such as inflammatory bowel disease and multiple sclerosis. The bacteria essentially uses the bodies immune response, designed to destroy bad bacteria, to its advantage.

The study
First, the researchers aimed to examine B. fragilis's symbiotic relationship with the gut by physically looking at the locations where the bacteria reside. Using electron microscopy imaging on samples of mouse intestines, the team was able to see that B. fragilis clumps together in aggregates deep within the thick layer of mucus lining the gut, nestled close to the epithelial cells that line the surface of the intestine.

Click to Enlarge
Electron microscopy image of the mouse gut,
showing B. fragilis aggregating close to epithelial cells
that make up the lining of the gut. 
Credit: Mazmanian laboratory

Donaldson and his collaborators theorized that this spatial niche is necessary for a single species to settle in and establish a stable foothold.

The team then aimed to determine what mechanisms allow B. fragilis to colonize such a niche within the gut. They found that each B. fragilis bacterium is encased in a thick capsule made of carbohydrates. The capsule is typically associated with pathogens (bad bacteria) attempting to cloak themselves from recognition and attack from the body's immune system. Mutant bacteria lacking this capsule cannot aggregate and do not inhabit the mucosal layer.

Thus, the researchers theorized that capsular carbohydrates are necessary for B. fragilis strains to monopolize their niche in the gut.

However, bacterial capsules are largely related to an immune response to pathogenic bacteria, therefore, there is also an immune response to the B. fragilis capsule. Antibodies and immune proteins (immunoglobulin or IgA) that typically grab onto bad bacteria, with the aim to destroy them, were also binding to the B. fragilis. This would typically mean death to the bacteria.

In the case of B. fragilis, the researchers found that it helped the bacteria stick to epithelial cells. Furthermore, in mice that lacked IgA, the bacterium was less successful at colonizing the surface of the intestine and maintaining long-term stability.

Therefore, the researchers state that the IgA response helps the B. fragilis anchor itself to the epithelial surface, which provides an advantage.

“The study of immunology has mainly been in the context of pathogenic bacteria. But there are trillions of bacteria in the gut, and most of the time none of them are making you sick. Our study shows that there is active immune recognition of these bacteria, but it helps rather than hinders them. This suggests that the immune system is more than just a defense system and antibodies are more than just weapons,” notes Donaldson.

Future research
In future work, the researchers plan to study how the gut's antibody response arises in the first place and why it helps B. fragilis while other antibodies hurt bacteria. Ultimately, this work could be used to improve colonization by other beneficial bacteria, as through the use of probiotics.

In previous news, NutritionInsight has reported on the link between the microbiome and brain diseases.

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