<i>In situ</i> Analysis of Mucus Residing Bacterial Community Reveals an Ecological Niche Key for Gut Microbiome Stability

Abstract

Colonic mucus bacterial communities are critical for determining disease pathology and promoting colonization resistance. Yet the key ecological properties of mucus resident communities that make them crucial for maintaining homeostatic microbiome function remain poorly defined. Using an approach that combine in situ hybridization, laser microdissection and 16s rRNA sequencing of spatially distinct regions of the mouse gut lumen, we discovered that the microbial community embedded in the mucus layer is structurally and compositionally distinct and drives stability of the gut microbiome. Structurally, the mucus residing microbial community had a higher density of bacteria than in the lumen and formed a biofilm-like structure whose integrity was dependent on Gram-positive commensals. Compositionally the dense mucus community excluded bacteria belonging to phylum Proteobacteria. Additionally, the dense bacterial community in the mucus was significantly more diverse and consisted of bacterial species that were unique to it. Upon antibiotic treatment, the species-rich and dense bacterial community in the mucus lost fewer Firmicutes and showed smaller bloom of Proteobacteria compared to the lumen. Taken together our work discloses a crucial role for the mucus layer in promoting stability of the gut microbiome in the perfused intestinal ecosystem by spatially entrenching unique and diverse bacterial species.