Bifidobacterial genes upregulated by resistant starch investigated using multi-omics have orthologs in infant gut isolates

Bifidobacterium species and strains are key members of the human gut microbiota, appearing soon after birth and persisting into adulthood. Resistant starch is an important dietary substrate for adult-associated bifidobacteria, where its fermentation supports host health. However, less is known about how different starch structures interact with bifidobacteria. Here we show that growth kinetics and gene expression differ depending on starch structure. Using detailed growth assays, genomics, and metabolomic analyses, bifidobacterial starch hydrolysis capabilities were closely associated with their CAZyme profiles. In one isolate of Bifidobacterium globosum, we identified a gene cluster encoding three multi-functional amylase enzymes complemented by several starch-binding modules, the genes and proteins of which were significantly upregulated in response to starch. Homologs of genes in the cluster were found in the genomes of bifidobacterial isolates from weaning infants providing insights into their role in the maturation process of the microbiota. Uncovering mechanisms of metabolic interaction between starch structures and bifidobacteria underscores the importance of this ecological function and potential health implications.