Many childhood diseases such as autism spectrum disorders, allergic disease, and obesity are on the increase. Although environmental factors are thought to play a role in this increase. The mechanisms at play are unclear but increasing evidence points to an interaction with the gastrointestinal microbiota as being potentially important. Recently this community of bacteria and perturbation of its colonization in early life has been linked to a number of diseases. Many factors are capable of influencing this colonization and ultimately leading to an altered gut microbiota which is known to affect key systems within the body. The impact of the microbial composition of our gastrointestinal tract on systems outside the gut is also becoming apparent. Here we highlight the factors that are capable of impacting on microbiota colonization in early-life and the developing systems that are affected and finally how this may be involved in the manifestation of childhood diseases.

A highly regulated crosstalk exists between the immune and neuroendocrine systems with the altered immune responses in stress-related disorders being a valid example of this interaction. The Wister Kyoto (WKY) rat is an animal model with a genetic predisposition towards an exaggerated stress response and is used to study disorders such as depression and irritable bowel syndrome (IBS), where stress plays a substantial role. The impact of a lipopolysaccride (LPS) immune challenge has not yet been investigated in this animal model to date. Hence our aim was to assess if the stress susceptible genetic background of the WKY rat was associated with a differential response to an acute immune challenge. Central and peripheral parameters previously shown to be altered by LPS administration were assessed. Under baseline conditions, WKY rats displayed visceral hypersensitivity compared to Sprague Dawley (SD) control rats. However, only SD rats showed an increase in visceral sensitivity following endotoxin administration. The peripheral immune response to the LPS was similar in both strains whilst the central neurochemistry was blunted in the WKY rats. Sickness behaviour was also abrogated in the WKY rats. Taken together, these data indicate that the genetic background of the WKY rat mitigates the response to infection centrally, but not peripherally. This implies that heightened stress-susceptibility in vulnerable populations may compromise the coordinated CNS response to peripheral immune activation.

Summary Visceral hypersensitivity (VH) is a hallmark of many functional gastrointestinal disorders including irritable bowel syndrome and is categorized by a dull, diffuse sensation of abdominal pain. Recently, the gut microbiota has been implicated in VH in male mice, but the effects in females have yet to be explored fully. To this end, we now show that somewhat surprisingly, female germ-free mice have similar visceral pain responses to colorectal distension (CRD) as their conventional controls. However, we show that although sensitivity to CRD is estrous cycle stage-dependent in conventional mice, it is not in germ-free mice. Further, ovariectomy (OVX) induced VH in conventional but not germ-free mice, and induced weight gain regardless of microbiota status. Finally, we show that estrogen-replacement ameliorated OVX-induced VH. Taken together, this study provides evidence for a major role of female sex hormones and the gut microbiota in sensation of visceral pain in females.