Modulation of visceral sensitivity by faecal microbiota transplantation (FMT): the active role of gut microbiota in the persistence of abdominal pain

Background: Recent findings linked gastrointestinal disorders characterized by abdominal pain to gut microbiota composition. The present work aimed to evaluate the power of gut microbiota as a visceral pain modulator and, consequently, the relevance of its manipulation as a therapeutic option in reversing the persistence of visceral hypersensitivity consequent to colitis induced by the intra-rectal injection of 2,4-dinitrobezenesulfonic acid (DNBS) in rats. Results: The effect of faecal microbiota transfer (FMT) from viscerally hypersensitive DNBS and naïve donors was evaluated in control rats after an antibiotic-mediated microbiota depletion. FMT from DNBS donors induced a long-lasting visceral hypersensitivity in control rats. Pain threshold trend correlated with major modifications in the composition and structure of the gut microbiota at phylum (Proteobacteria and Firmicutes to Bacteroides ratio) and family levels (Enterobacteriaceae, Akkermansiaceae and Lachnospiraceae). Acetic acid was significantly increased in the recipients FMT from DNBS donors. Gut cytokine profile, as well as tryptophan metabolism were similarly altered after FMT from both DNBS and naïve donors. By contrast, no significant alterations of colon histology, permeability and monoamines levels were detected. Finally, following FMT from healthy donors to DNBS-treated animals, a counteraction of persistent visceral pain was achieved. Conclusions: The present results provide novel insights into the relationship between intestinal microbiota and visceral hypersensitivity, highlighting the therapeutic potential of microbiota modulation on persistent abdominal pain.