Probiotic Bifidobacterium bifidum G9-1 attenuates 5-fluorouracil-induced intestinal mucositis in mice via suppression of dysbiosis-related secondary inflammatory responses.

Bifidobacterium, a major component of the intestinal microbiota, has been clinically used for the treatment of diarrhoea and constipation. 5-Fluorouracil (5-FU), widely used for cancer chemotherapy, is known to frequently induce intestinal mucositis accompanied by severe diarrhoea. The present study examined the effect of Bifidobacterium bifidum G9-1 (BBG9-1) on 5-FU-induced intestinal mucositis in mice. Intestinal mucositis was induced by repeated administration of 5-FU for 6 days. BBG9-1 was administered orally once daily for 9 days, beginning 3 days before the onset of 5-FU treatment. Repeated administration of 5-FU caused severe intestinal mucositis, characterised by shortening of villi and destruction of crypts, accompanied by increases in intestinal myeloperoxidase activity and inflammatory cytokine expression, body weight loss, and diarrhoea on day 6. Daily administration of BBG9-1 significantly reduced the severity of intestinal mucositis and inflammatory responses and tended to attenuate clinical symptoms. In contrast, BBG9-1 failed to prevent apoptosis induction on day 1 after the first 5-FU administration. The structure of the intestinal microbiota, as analysed by weighted UniFrac distance, was largely altered by 5-FU treatment, but this change was mitigated by daily administration of BBG9-1. Moreover, 5-FU treatment decreased the abundance of Firmicutes and increased the abundance of Bacteroidetes, but these responses were also significantly inhibited by daily administration of BBG9-1. These results suggest that BBG9-1 has an ameliorative effect against 5-FU-induced intestinal mucositis through the attenuation of inflammatory responses via improve dysbiosis. BBG9-1 could be useful for the prevention of intestinal mucositis during cancer chemotherapy.

The Effects of Metformin on the Gut Microbiota of Patients with Type 2 Diabetes: A Two-Center, Quasi-Experimental Study.

Metformin is reported to affect human gut microbiota; however, the nature of this association in Japanese patients with type 2 diabetes mellitus (T2DM) is unknown. We enrolled 31 patients with T2DM who took metformin for the first time in this study. We compared them before and after four weeks of taking metformin. Fecal samples were collected and 16S rDNA sequences were performed to identify the gut microbiota. Blood samples and Gastrointestinal Symptom Rating Scale (GSRS) questionnaire results, denoting gastro-intestinal symptoms, were also collected. In the whole-group analysis, no significant differences were found at the phylum level. In a subgroup of 21 patients that excluding those using medications affecting gut microbiota, there was a significant decrease of the phylum Firmicutes (p = 0.042) and of the ratio of the Firmicutes and Bacteroidetes abundances (p = 0.04) after taking metformin. Changes in abdominal pain (r = -0.56, p = 0.008) and regurgitation (r = -0.53, p = 0.01) were associated with Parabacteroides. Despite there being no direct association with abdominal symptoms, our study revealed that the composition of gut microbiota in Japanese individuals with T2DM partially changed after starting metformin.