Post-infection disorders of gut-brain interaction (PI-DGBI) are a subset of chronic gastrointestinal disorders triggered by acute infectious gastroenteritis. These conditions impose a significant burden on patients’ quality of life.
This study aimed to determine the prevalence of PI-DGBI and assess associated risk factors among participants in the Rome Foundation Global Epidemiology Study.
Data were extracted from an online survey involving 54 127 participants across 26 countries. PI-DGBI were diagnosed based on self-reported gastrointestinal symptoms following acute gastroenteritis. Statistical analyses included multivariate logistic regression to identify factors associated with PI-DGBI and comparisons with DGBI not associated with infection.
Of 21 713 individuals with at least one DGBI, 987 (10.5%) were classified as having PI-DGBI. PI-DGBI prevalence varied geographically, with the highest rates in Asia (7.1%) and Latin America (6.4%). Younger age, male sex, urban residence, anxiety and higher somatic symptom scores were positively associated with subjects reporting PI-DGBI, while female sex and rural living had negative associations. Subjects with PI-DGBI reported more severe psychological and physical health impairments and distinct gastrointestinal profiles, including higher rates of functional dyspepsia (32.2%), irritable bowel syndrome (23.5%) and anorectal disorders (35.3%).
PI-DGBI represents a significant subset of DGBI, with distinct sociodemographic and clinical characteristics. These findings highlight the role of acute gastroenteritis in triggering the onset of long-term gastrointestinal disorders and underscore the need for targeted interventions to mitigate its impact on patient health.
Dipeptidyl peptidase-4 inhibitors (DPP-4is) have been reported to exhibit therapeutic effects in Parkinson’s disease (PD), increasing their potential for drug repurposing. One aspect of PD pathogenesis is thought to be associated with the gut-brain axis, where α-synuclein from the gut is transmitted to the brain via the vagus nerve (VN).
We explored whether sitagliptin, a DPP-4i, exhibits a protective effect in a low-dose rotenone-treated gut-brain axis-associated PD model.
To explore the effect of sitagliptin, we used the oral rotenone-treated mouse model, which showed spreading of pathological α-synuclein from the intestine in a stereotypic manner via the VN into the midbrain with motor deficits.
Sitagliptin mitigated rotenone-induced gut inflammation and toll-like receptor 2 (TLR2) expression, reduced α-synuclein accumulation in the gut, VN and brain and lessened neuronal loss in the medulla and midbrain with recovery of motor performance. In addition, sitagliptin suppressed inflammation in response to a TLR2 agonist and rotenone in macrophages, enteric glial cells and enteroendocrine cell lines in vitro. In secretin tumour cell 1, an enteroendocrine cell line, sitagliptin also decreased rotenone-induced endogenous α-synuclein levels. The beneficial effects of sitagliptin were maintained even under glucagon-like peptide-1 receptor blockade. Notably, sitagliptin significantly altered the gut microbiome, shifting towards a profile that may counteract PD pathology.
These findings demonstrated that sitagliptin alleviated α-synuclein deposition in the gut and brain through modulation of TLR2-mediated inflammation and altered the gut microbiome composition towards a more favourable profile, which indicates that DPP-4is can offer a novel therapeutic avenue for managing PD.