Integrated fecal microbiome-metabolome signatures reflect stress and serotonin metabolism in irritable bowel syndrome.

To gain insight into the complex microbiome-gut-brain axis in irritable bowel syndrome (IBS), several modalities of biological and clinical data must be combined. We aimed to identify profiles of fecal microbiota and metabolites associated with IBS and to delineate specific phenotypes of IBS that represent potential pathophysiological mechanisms. Fecal metabolites were measured using proton nuclear magnetic resonance (1H-NMR) spectroscopy and gut microbiome using shotgun metagenomic sequencing (MGS) in a combined dataset of 142 IBS patients and 120 healthy controls (HCs) with extensive clinical, biological and phenotype information. Data were analyzed using support vector classification and regression and kernel t-SNE. Microbiome and metabolome profiles could distinguish IBS and HC with an area-under-the-receiver-operator-curve of 77.3% and 79.5%, respectively, but this could be improved by combining microbiota and metabolites to 83.6%. No significant differences in predictive ability of the microbiome-metabolome data were observed between the three classical, stool pattern-based, IBS subtypes. However, unsupervised clustering showed distinct subsets of IBS patients based on fecal microbiome-metabolome data. These clusters could be related plasma levels of serotonin and its metabolite 5-hydroxyindoleacetate, effects of psychological stress on gastrointestinal (GI) symptoms, onset of IBS after stressful events, medical history of previous abdominal surgery, dietary caloric intake and IBS symptom duration. Furthermore, pathways in metabolic reaction networks were integrated with microbiota data, that reflect the host-microbiome interactions in IBS. The identified microbiome-metabolome signatures for IBS, associated with altered serotonin metabolism and unfavorable stress response related to GI symptoms, support the microbiota-gut-brain link in the pathogenesis of IBS.

Significantly higher rates of multiple and proximally located adenomas among patients with diabetes mellitus: A cross-sectional population-based study.

BACKGROUND: Diabetes mellitus (DM) is associated with a greater risk for colorectal cancer (CRC). OBJECTIVE: The objective of this article is to examine the endoscopic phenotype and histopathology of colorectal polyps in patients with vs without DM. METHODS: We conducted a cross-sectional study of patients who underwent colonoscopy at our university hospital and who completed a questionnaire. We collected endoscopy and histopathology data regarding colorectal adenomas and serrated polyps. Cox regression analyses were used to estimate adjusted prevalence ratios (PRs). RESULTS: We examined a total of 3654 patients (mean age (SD): 62 (12) years, 47% males). Of them, 360 (9.9%) had DM. Overall, the prevalence of colorectal adenomas (42% vs 32%, p < 0.01), multiple (≥3) adenomas (12% vs 7%, p = 0.01) and proximal adenomas (30% vs 19%, p < 0.01) was higher in patients with vs without DM. Multivariable analysis showed that the prevalence of adenomas (PR 1.17, 95% CI; 1.02-1.34), multiple (PR 1.37, 95% CI; 1.00-1.86) and proximal (PR 1.37, 95% CI; 1.16-1.62) adenomas was higher in patients with vs without DM, especially in men. CONCLUSION: Patients with DM harbor more frequently multiple and proximal adenomas than those without DM. Close colonoscopic surveillance of DM patients is important to maximize the effectiveness of colonoscopic CRC prevention.