Abstract: The perception of visceral pain is a complex process involving the spinal cord and
higher order brain structures. Increasing evidence implicates the gut microbiota as a key regulator
of brain and behavior, yet it remains to be determined if gut bacteria play a role in visceral
sensitivity. We used germ-free mice (GF) to assess visceral sensitivity, spinal cord gene expression
and pain-related brain structures. GF mice displayed visceral hypersensitivity accompanied by
increases in Toll-like receptor and cytokine gene expression in the spinal cord, which were
normalized by postnatal colonization with microbiota from conventionally colonized (CC). In GF
mice, the volumes of the anterior cingulate cortex (ACC) and periaqueductal grey, areas involved in
pain processing, were decreased and enlarged, respectively, and dendritic changes in the ACC
were evident. These findings indicate that the gut microbiota is required for the normal visceral
pain sensation.
