Objective: Irritable bowel syndrome (IBS) is associated with alterations along the brain-gut-microbiota axis. Previous studies have suggested a parallel segregation of microbial features and psychological burden in IBS. This study aimed at exploring the microbial correlates of psychological distress in patients with IBS. Methods: Forty-eight patients with IBS (Rome III criteria, M (SD) age = 42 (15) years, 35 female, 25 diarrhea-dominant, 5 constipation-dominant, and 18 alternating-type IBS) were assessed for psychological and clinical variables with validated questionnaires, fecal samples underwent microbial 16S rRNA analyses (regions V1–2). Microbial analyses comprised examination of alpha and beta diversity, correlational analyses of bacterial abundance and comparisons among subgroups defined by thresholds of psychological and IBS symptom variables, and machine learning to identify bacterial patterns corresponding with psychological distress. Results: Thirty-one patients (65%) showed elevated psychological distress, 22 (31%) anxiety, and 10 depression (21%). Microbial beta diversity was significantly associated with distress and depression (q = .036 each, q values are p values false discovery rate–corrected for multiple testing). Depression was negatively associated with Lachnospiraceae abundance (Spearman's ρ = −0.58, q = .018). Patients exceeding thresholds of distress, anxiety, depression, and stress perception showed significantly higher abundances of Proteobacteria (q = .020–.036). Patients with anxiety were characterized by elevated Bacteroidaceae (q = .036). A signature of 148 unclassified species accounting for 3.9% of total bacterial abundance co-varied systematically with the presence of psychological distress. Conclusions: Psychological variables significantly segregated gut microbial features, underscoring the role of brain-gut-microbiota interaction in IBS. A microbial signature corresponding with psychological distress was identified. Clinical Trial Registration: ClinicalTrials.gov identifier NCT02536131, retrospectively registered.

Irritable bowel syndrome (IBS) is a disorder with brain-gut-microbiome alterations. Gut-directed hypnotherapy (GHT) has been shown to improve quality of life and symptoms in IBS. This therapy targets psychological coping, central nervous processing and brain-gut interaction. Studies have also demonstrated effects of hypnosis on intestinal transit and the mucosal immune system. So far, no study has examined the effect of GHT on the intestinal microbiome. This study aimed at examining microbial composition, IBS symptoms, and psychological distress before and after GHT. Methods: Fecal samples were collected from 38 IBS patients (Rome-III criteria, mean age 44 years, 27 female, 11 male, 22 diarrhea-dominant, 12 alternating-type and 4 constipation-dominant IBS) before and after 10 weekly group sessions of GHT. Assessments in psychological (perceived stress, PSQ; psychological distress, HADS-D; quality of life, visual analogue scales) and IBS symptom-related variables (IBS severity, IBS-SSS; single symptoms, visual analogue scales) were performed with validated questionnaires. Fecal samples underwent microbial 16S rRNA analyses (regions V1–2). Results: Microbial alpha diversity was stable before and after GHT (chao1 2591 ± 548 vs. 2581 ± 539, p = 0.92). No significant differences were found in relative bacterial abundances but trends of reduced abundance of Lachnospiraceae 32.18 (4.14–39.89) Median (Q1–Q3) vs. 28.11 (22.85; 35.55) and Firmicutes: Bacteroidetes ratio after GHT were observable. Significant reductions in symptom severity (323 (266–371) vs. 264 (191–331), p = 0.001) and psychological distress 17.0 (12.6–21.8) vs. 12.0 (8.3–18.0), p = 0.001, and increased well-being were found after GHT. Adequate relief after therapy was reported by 32 (84%) patients. Conclusion: Reductions in IBS symptoms and psychological burden were observed after gut-directed hypnotherapy, but only small changes were found in intestinal microbiota composition. The findings suggest that hypnosis may act by central nervous impact and other factors largely independent from microbiota composition modulating the brain-gut axis, possibly alterations in vagus nerve functioning and microbiota metabolism.