Polysaccharide utilization loci in Bacteroides determine population fitness and community-level interactions. Feng et al.
Polysaccharide utilization loci (PULs) in the human gut microbiome have critical roles in shaping human health and ecological dynamics. We develop a CRISPR-FnCpf1-RecT genome-editing tool to study 23 PULs in the highly abundant species B. uniformis (BU). We identify the glycan-degrading functions of multiple PULs and elucidate transcriptional coordination between PULs that enables the population to adapt to the loss of PULs. Exploiting a pooled BU mutant barcoding strategy, we demonstrate that the in vitro fitness and the colonization ability of BU in the murine gut is enhanced by deletion of specific PULs and modulated by glycan availability. We show that BU PULs can mediate complex glycan-dependent interactions with butyrate producers that depend on the mechanism of degradation and the butyrate producer glycan utilizing ability. In sum, PULs are major determinants of community dynamics and butyrate production and can provide a selective advantage or disadvantage depending on the nutritional landscape.