Differences in Gut Mucus Microbiota Precede Dysbiosis in Inflammatory Bowel Disease

Impaired tolerance to the gut microbiota is associated with inflammatory bowel diseases (IBD), such as Crohn’s disease and Ulcerative colitis. The microbiota is complex and in the colon resides in the gut lumen and the thick outer mucus layer covering the epithelium, leaving the inner mucus sterile. The mucus bacteria are likely to have most impact on the epithelium and underlying lamina propria. Studies investigating microbiota in IBD pathogenesis have mainly focused on stool microbial analysis leaving mucus bacteria understudied.  To determine the importance of mucus bacteria in IBD development, we investigated colitis progression in the mdr1a^-/- spontaneous model of colitis. Microbial differences between mdr1a^-/- and wild-type littermate controls were evident before colitis onset but restricted to the mucus. Despite mucus microbial composition differing between controls and mdr1a^-/-mice, bacterial location and mucus thickness were similar. Upon emergence of early inflammation in mdr1a^-/- mice, differences in bacterial composition extended from the mucus to the luminal compartment. Furthermore, the mucus layer became thinner. Although bacterial load was not increased overall during colitis onset, bacterial localization with respect to host tissue was altered with bacteria penetrating the inner mucus. Our results show that microbial dysbiosis starts in specific niches before IBD onset.