COMPARATIVE GENOMICS AND FUNCTIONAL ANALYSIS OF BIFIDOBACTERIUM CARBOHYDRATE ACTIVE ENZYMES IN HUMAN MILK OLIGOSACCHARIDES UTILIZATION

Abstract

The gut microbiota in early life influences host health and the risk of chronic diseases, including asthma. The infant gut microbiota composition is shaped by multiple determinants such as birth mode, breastmilk feeding practices, and the environment. Previous studies have identified specific taxa associated with protection from atopy and asthma including Bifidobacterium. Human Milk Oligosaccharides (HMOs) are an abundant component of breastmilk; however, infants cannot digest them as they lack the necessary enzymes. Bifidobacterium produce specific glycoside hydrolases (GHs) that hydrolyze HMOs and release short chain fatty acids, which are beneficial for the infants. The colonization of B. longum subsp. infantis (B. infantis) in the first year of life is predicted to be protective against asthma development. However, there are other Bifidobacterium species or B. longum subspecies that colonize the infant gut as well as strain diversity in GHs. In this study, I used both comparative genomics and phenotypic screening of 118 Bifidobacterium strains. Comparative genomics identified strain specific differences in GHs and phenotypic screening showed variability in HMOs degradation among strains. By constructing sequence similarity networks for GHs involved in HMO degradation, I assigned subtypes to GH proteins. These subtypes were hypothesized to have different functions and substrate specificity. Using the machine learning data of the GH subtype profiles combined with HMO utilization assay data, I mapped specific degradation reactions to GH subtypes. Lastly, metagenomic reads were mapped against selected Bifidobacterium strains and GH subtype genes. Although B. infantis is associated with a reduced asthma risk, I observed that this strain was also abundant in some subjects with an asthma phenotype. Overall, our metagenomic read mapping analysis suggests that asthma development is not solely determined by one Bifidobacterium strain or GH subtype. Instead, it appears that multiple factors contribute to asthma risk.