Defect in TLR5 expression enhances spontaneous visceral hypersensitivity and decreases anxiety behavior

Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Diseases (IBD), intestinal disorders associated with colonic hypersensitivity (CHS) and abdominal pain, are believed to result in part from breakdown of homeostasis between intestinal microbiota and the mucosal immune system. In addition, such patients also suffered from several associated disorders, such as anxiety and depression. Among alterations in immune innate function, some are related to the Toll-Like Receptor 5 (TLR5) responsible for the primary defense of the organism against microbial intruders especially potentially virulent invasive bacteria expressing flagellin. Mice deficient for TLR5 (TLR5KO) have been described to uniformly exhibit altered microbiota and increased levels of inflammatory markers. The aim of this work was to assess visceral sensitivity of TLR5KO mice and to determine if visceral pain was associated with anxiety and depressive disorders.

            TLR5KO mice uniformly exhibited greater CHS in comparison to their WT littermates, revealed by an increase of the visceromotor activity of the abdominal muscle in response to a colorectal distention. Surprisingly, TLR5KO mice showed decreased anxiety while depressive phenotype and cognitive disorders were not observed.

This study demonstrated an involvement of TLR5 and innate immunity in CHS and anxiety behavior. Such impact could be direct, depending on its expression at the nervous level, or indirect and related to its role in the modulation of the intestinal microbiota.