Strategies to control colonization of Bacteroides in the intestine

The human gut contains a diverse microbial community known as the microbiota. The microbiota consists of several hundred to thousands of different bacterial species whereof the genus of Bacteroides is one of the most abundant. In most individuals, Bacteroides will become a substantial part of microbiota after infancy correlating with the introduction of dietary fibers and the cessation of breastfeeding. Bacteroides species are recognized for a large capacity of utilizing complex carbohydrates including host-derived glycans such as mucus and Human Milk Oligosaccharide (HMO). How the HMO-utilizing abilities of Bacteroides affect their abundance in vivo is not well understood. We investigated if an HMO supplement added to the drinking water of conventional mice affected their microbiota. We reported that the family of Bacteroidaceae and specifically the genus of Phocaeicola (formerly part of Bacteroides) increased in both absolute and relative abundance upon HMO supplementation and showed a concurrent decrease in the genus of the butyrate-producing Lacrimispora. The decrease in Lacrmispora correlated with a decrease in fecal levels of butyrate which might be important for gut health (Manuscript I).

Gut-adapted species such as Bacteroides are candidates for next-generation probiotics (NGP). We suggested that HMOs might be a means to selectively increase the abundance of specific Bacteroides species in the gut. We isolated Bacteroidales species from human donors to obtain a large and diverse strains collection and expand the potential for strain engineering. Out of this strain collection, we genome-sequenced four strains and reported the transfer of a 94.2kb mobile genetic element between four species of Bacteroides co-residing in the gut of a single human donor. The mobile element contained a Type VI secretion system (T6SS) found to confer antagonism between Bacteroides in the gut. We identified the T6SS as a possible target for in situ engineering of Bacteroides. Lastly, as a proof-of-concept study, we conferred tetracycline resistance in the T6SS of a Bacteroides strain and showed the in vitro transfer of the mobile element to two different species of Bacteroides recipients (Manuscript II). The studies reported in this Ph.D. contribute to a better understanding of the Bacteroides species in the gut ecosystem and further aid in the development of Bacteroides as a NGP.