Symbionticism: Gut-Microbe Homeostasis in Mammals

Out of many, one.

Animals harbor a melting pot of beneficial microbes in their guts and they confer numerous fitness adaptations.

In an effort to isolate the molecular mechanisms that underpin highly specific host-microbe interactions in this community, a recent paper in Nature studied the intimate interplay between gut microbes and their hosts. This research concentrated on identifying the key colonization genes in the bacteria that make a home out of mouse guts.

First, they showed that vertebrate beneficial microbes, like that of Bacteroides fragilis, exhibit colonization resistance against themselves, i.e., resident clones inside the mouse gut are resistant to inoculations of additional clones, as if there is a shortage of space or nutrients and the bacteria know it. However, clones of one bacterial species readily get displaced by other species of Bacteroides. Its kind of like you living in a home and keeping other people out of it by not opening the door. But if a pack of chimpanzees knock on the door, and you dont notice them and open it, they could easily outcompete you and cause you to flee out your windows. So what is the molecular mechanism of the bacteria that allows them to detect self and keep the door closed?

By iteratively inserting genetic regions of Bacterioides fragilis into the genome of B. vulgatus and inoculating these transgenic bacteria back into B. fragilis-infected guts, the team found the specific regions of the genome that control colonization inhibition against itself. The genes encode SusC and SusD-like proteins involved in outer membranes. They likely bind to starches. Here they were termed commensal colonization factors. Not sure about the use of the word "commensal" here as these bacteria do play a beneficial role in fitness.

These genes are highly expressed in bacteria tethered to the colon and appear to lack expression in in vitro laboratory culture. They also hang out in mucosal tissue and particularly prefer the crypts of the colon. The wild type bacteria better colonize these crypts than the mutants carrying deletions in these same genes. And even after low dose antibiotic treatment, crypt-associated clones of Bacteroides were still present in the host colon, whereas those that were mutated in these key genes were washed away by the antibiotics. Seems like the wild type beneficial bacteria are indeed better niche colonizers.

They conclude that these genes evolved to promote long-term symbiosis between specific strains of bacteria an the host gut. I question whether they know anything about long-term symbiosis as these studies were not done in a comparative functional context. I do agree, however, with their last statement:

Discovery of a molecular mechanism for colonization fitness by gut bacteria provides a glimpse into the evolutionary forces that have shaped the assembly and dynamics of the human microbiome.

An interesting after-thought on this study that appeared in this press release is that many typical gut bacteria do not have genes similar to commensal colonization factors. So how universal this mechanism will be is up for future study.

Source: Bacterial colonization factors control specificity and stability of the gut microbiota by Lee et al, 2013, Nature.

Video from the senior author describing this research