Effect of Japanese traditional medication on males with diarrhea-predominant irritable bowel syndrome and gut microbiome: A single-arm prospective study

• We examined Kampo's effects on diarrhea-predominant irritable bowel syndrome (IBS-D). • Male IBS-D symptoms were decreased after hangeshashinto and rikkunshito treatment. • IBS-related quality of life improved and anxiety decreased after treatment. • IBS-D patients' gut microbiota dysbiosis recovered post-treatment. • We identified gut microbial species altered by Kampo treatment. Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common disorder of gut-brain interaction. In Japan, IBS-D is treated using Japanese traditional medicine (Kampo medicine); however, its clinical effects and influence on the gut microbiome are unknown. The purpose of this study was 1) to compare the characteristics of IBS-D patients with healthy controls (HCs), and 2) to investigate the effect of Kampo medicine on the symptoms and gut microbiome of patients with IBS-D. We conducted two studies stepwise. First, we compared the clinical characteristics and gut microbiome of the patients with IBS-D to HCs. Second, we conducted a single-arm prospective clinical study to investigate the effectiveness and safety of Kampo treatment for IBS-D and its effects on gut microbiome alterations in patients with IBS-D. Newly diagnosed male patients with IBS-D received a four-week Kampo treatment (hangeshashinto or rikkunshito). Data on overall clinical improvement, scores on quality of life (QOL), gastrointestinal symptoms, diarrhea, anxiety, and depression were obtained. Fecal microbiomes were analyzed at four time points: (1) before treatment with remission; (2) before treatment with exacerbation; (3) after treatment; and (4) four weeks after treatment. Study 1: No significant difference was observed in the variety of gut microbiome (alpha diversity) between HCs and IBS-D patients. Study 2: After treatment, 81% of the patients with IBS-D showed clinical improvement. Compared with the baseline, significant improvement was observed in IBS-related QOL, diarrhea, and trait anxiety scores after treatment and after follow-up, with no adverse effects. Microbiome analysis revealed significantly increased alpha diversity, decreased Blautia abundance, and increased Oscillospira abundance after treatment and 4 weeks after treatment compared with those during the exacerbation period before Kampo treatment. Our study shows that no significant difference was observed in gut microbiome diversity between the patients with IBS-D and HCs. After Kampo treatment, abdominal symptoms and anxiety in male IBS-D patients were observed to improve and microbial diversity with specific microbial alterations appeared to be restored. These findings suggest that Kampo medicine could be considered as a potential approach for the symptoms and dysbiosis of IBS-D.