UC Santa Cruz

The human gut microbiota houses tremendous bacterial diversity and serves many functions, such as providing colonization resistance, affecting host immune system maturation, and breaking down complex host-ingested dietary fiber, which can have implications for host health. However, unlike the oral microbiota, where organized and well-structured bacterial communities have been observed in dental plaque, the bacterial distribution, interspecies community formation, and community-level interactions between species and strains in the gut are less well characterized. Although variable at the individual level, Bacteroides thetaiotaomicron (B. theta), a fiber generalist, is one of the most abundant and variable species in the human gut microbiota, making it a species of importance with respect to human health. Studies in the field have shown that many Bacteroides adhere to food fragments and dietary particles and form interspecific interactive relationships with other gut microbes. These observations raise the question of how a non-motile bacterium such as B. theta navigates the turbulent intestinal environment and forms interspecies interactions.In chapter one, we draw on existing evidence in the field to build a theoretical framework in which adhesion by Bacteroides and their interactive partners drives the formation of bacterial communities at the microscale by drawing interactive partners into proximity and preventing their separation on the adhesive substrate, thereby sustaining bacterial interaction. In chapter two, we focus on a previously uncharacterized B. theta Type V pilus encoded on a mobile genetic element, hypothesized to serve as the adhesin for galactan adhesion. Through genomics, proteomics, transcriptomics, and functional assays, we found that expression of this novel pilus did not assist adhesion; on the contrary, it disrupted glycan, host-cell, and auto/coaggregation, potentially by increasing the distance between cells. Lastly, in chapter three, we investigated the possibility of food-residue-adhesion-based bacterial community formation by studying two B. theta strains, both capable of adhering to the dietary polysaccharide galactan. Through coculturing assays and genome sequencing, we found that adhesion and catabolism are disconnected: a co-adhering, catabolism-competent strain can rescue a co-adhering, catabolism-deficient strain, and that the catabolism deficiency in B. theta DH4087 stems from the loss of a gh53, encoding an endo-1,4-β-galactanase.