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Background: Immune checkpoint inhibitors (ICIs) are crucial in cancer treatment; however, they carry the risk of immune-related adverse events (irAEs), such as enteritis. Case presentation: This study investigated the role of the gut microbiota during the onset and remission of irAE enteritis in a patient with stage IV melanoma undergoing anti-PD-1 and anti-CTLA-4 therapy. Following commencement of ICI treatment, the patient developed severe diarrhea and was diagnosed with grade 3 irAE enteritis. Steroid and probiotic treatments provided swift symptom relief and remission, as confirmed by reduced fecal calprotectin levels and gastrointestinal imaging. Microbiota diversity analysis conducted via 16S rRNA gene sequencing identified a decrease in Streptococcus prevalence with improvement in enteritis symptoms. Conversely, genera Fusobacterium, Faecalibacterium, Bacteroides, Prevotella, and Bifidobacterium showed increased representation after remission. These genera are associated with anti-inflammatory properties and fibrous substrate degradation, aiding gut health. Immunological assessment demonstrated fluctuations in cytokine expression and the modulation of costimulatory molecules, aligning with therapeutic interventions and microbiota alterations. Conclusions: Our findings indicate a significant correlation between gut microbiota and immune responses in irAE enteritis. This underscores the potential utility of microbiome profiling in predicting irAE occurrence and in providing treatment strategies, thereby promoting a more comprehensive approach to managing the adverse effects of ICIs. [ABSTRACT FROM AUTHOR]

Background and Aim: Fluoropyrimidines (FPs) are key drugs in many chemotherapy regimens; however, recipients are often prone to diarrhea due to gastrointestinal toxicity. Disruption of the intestinal epithelial barrier function by FPs leads to dysbiosis, which may exacerbate intestinal epithelial cell damage as a secondary effect and trigger diarrhea. However, despite studies on chemotherapy-induced changes in the intestinal microbiome of humans, the relationship between dysbiosis and diarrhea is unclear. In this study, we aimed to investigate the relationship between chemotherapy-induced diarrhea and the intestinal microbiome. Methods: We conducted a single-center prospective observational study. Twenty-three patients who received chemotherapy, including FPs as first-line chemotherapy for colorectal cancer, were included. Stool samples were collected before the start of chemotherapy and after one cycle of treatment to analyze intestinal microbiome composition and perform PICRUSt predictive metagenomic analysis. Results: Gastrointestinal toxicity was observed in 7 of 23 patients (30.4%), diarrhea was observed in 4 (17.4%), and nausea and anorexia were observed in 3 (13.0%). In 19 patients treated with oral FPs, the α diversity of the microbial community decreased significantly following chemotherapy only in the diarrheal group. At the phylum level, the diarrheal group showed a significant decrease in the abundance of Firmicutes and a significant increase in the abundance of Bacteroidetes with chemotherapy (p = 0.013 and 0.011, respectively). In the same groups, at the genus level, Bifidobacterium abundance was significantly decreased (p = 0.019). In contrast, in the non-diarrheal group, Actinobacteria abundance increased significantly with chemotherapy at the phylum level (p = 0.011). Further, Bifidobacterium, Fusicatenibacter, and Dorea abundance significantly increased at the genus level (p = 0.006, 0.019, and 0.011, respectively). The PICRUSt predictive metagenomic analysis revealed that chemotherapy caused significant differences in membrane transport in KEGG pathway level 2 and in 8 KEGG pathway level 3, including transporters and oxidative phosphorylation in the diarrhea group. Conclusion: Organic-acid-producing bacteria seem to be involved in diarrhea associated with chemotherapy, including FPs. [ABSTRACT FROM AUTHOR]

Background and Aim: Gut microbiota composition is associated with the pathogenesis of non‐alcoholic fatty liver disease. However, the association between gut microbiota composition and non‐alcoholic fatty liver disease in non‐obese patients remains unclear. We compared clinical parameters and gut microbiota profiles of healthy controls and non‐obese and obese patients with non‐alcoholic fatty liver disease. Methods: We examined the clinical parameters and gut microbiota profiles by 16S rRNA sequences and short‐chain fatty acid levels in fecal samples from 51 non‐obese patients with non‐alcoholic fatty liver disease (body mass index <25 kg/m2) and 51 obese patients with non‐alcoholic fatty liver disease (body mass index ≥30 kg/m2) who underwent pathological examination and 87 controls at five hospitals in Japan. Results: Although no significant differences between the non‐obese and other groups were observed in alpha diversity, a significant difference was found in beta diversity. We observed a significant decrease in serum alanine aminotransferase levels, Eubacterium population, and butyric acid levels in non‐obese patients with non‐alcoholic fatty liver disease compared with those in obese patients with non‐alcoholic fatty liver disease. A significant negative correlation was found between the stage of hepatic fibrosis and Eubacterium abundance in non‐obese patients with non‐alcoholic fatty liver disease. Conclusions: The decrease in the abundance of Eubacterium that produces butyric acid may play an important role in the development of non‐alcoholic fatty liver disease in non‐obese individuals. This study was registered at the University Hospital Medical Information Network clinical trial registration system (UMIN000020917). [ABSTRACT FROM AUTHOR]

Diarrhea is largely caused by dysbiosis accompanying the hyperproliferation of Escherichia coli (E. coli). While current treatments can resolve the symptoms, they cannot suppress the proliferation of pathogenic bacteria in the intestine. Probiotics have numerous beneficial effects on host health, including restoring the balance of the intestinal microbiota. This study investigated the effect of the probiotic Bifidobacterium bifidum G9‐1 (BBG9‐1), which is active in intestinal dysbiosis, in the incidence of diarrhea, in the composition of the intestinal microbiota, and in the intestinal tissue of a rat model of phytohemagglutinin (PHA)‐induced diarrhea. The rats were treated with PHA, with and without BBG9‐1, and the microbiota composition throughout the intestine and stool was examined using high‐throughput 16S rRNA sequencing. In line with previous reports, PHA administration caused diarrhea as well as dysbiosis due to E. coli hyperproliferation. Histological findings indicated that the jejunal villus length was shortened. Rats that received BBG9‐1 showed clear improvements in dysbiosis, diarrhea symptoms, and jejunal villus length. Principal coordinates analysis demonstrated the microbiota profile to be more similar between the BBG9‐1 and normal groups than between the PHA and normal groups. These results indicated that BBG9‐1 suppresses the hyperproliferation of E. coli and restores the jejunal villus length, thereby improving dysbiosis, and in turn, alleviating the symptoms of diarrhea. [ABSTRACT FROM AUTHOR]

Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-018-30943-3, published online 17 August 2018 The original version of this Article contained an error in the legend of Figure 4. The original article can be found online at https://doi.org/10.1038/s41598-018-30943-3. [Extracted from the article]

The aim of this research was to reveal the characteristics of gut microbiome altered by acarbose intervention in Japanese patients with type 2 diabetes (T2D) and its possible association with habitual dietary intake. Eighteen patients with T2D were administered acarbose for four weeks. The abundances of two major phyla, namely Actinobacteria and Bacteroidetes, were reciprocally changed accompanied by the acarbose intervention. There were also significant changes in the abundances of ten genera, including the greater abundance of Bifidobacterium, Eubacterium, and Lactobacillus and the lower abundance of Bacteroides in the group after the intervention than that before the intervention. Hierarchical clustering of habitual dietary intake was performed based on the pattern of changes in the gut microbiota and were classified into distinct three clusters. Cluster I consisted of sucrose, cluster II mainly included fat intake, and cluster III mainly included carbohydrate intake. Moreover, the amount of change in Faecalibacterium was positively correlated with the intake of rice, but negatively correlated with the intake of bread. The intake of potato was negatively correlated with the amount of change in Akkermansia and Subdoligranulum. Acarbose altered the composition of gut microbiome in Japanese patients with T2D, which might be linked to the habitual dietary intake. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Although dysbiosis is likely to disturb the mucosal barrier system, the mechanism involved has remained unclear. Here, we investigated alterations of colonic mucosal permeability and tight junction (TJ) molecules in mice with antibiotic-induced dysbiosis. Mice were orally administered vancomycin or polymyxin B for 7 days, and then fecal samples were subjected to microbial 16S rRNA analysis. The colonic mucosal permeability was evaluated by chamber assay. The colonic expression of TJ molecules and cytokines was examined by real-time RT-PCR, Western blotting, and immunohistochemistry. Caco2 cells were stimulated with cytokines and their transepithelial electric resistance (TEER) was measured. Vancomycin-treated mice showed significantly lower gut microbiota diversity than controls, and the same tendency was evident in polymyxin B-treated mice. The colonic mucosal permeability was significantly elevated in both vancomycin- and polymyxin B-treated mice. The expression of claudin 4 in the colonic mucosa was decreased in both vancomycin- and polymyxin B-treated mice. Colonic expression of TNF-α and/or IFN-γ was significantly increased in mice that had been administered antibiotics. TNF-α and IFN-γ stimulation dose-dependently decreased TEER in Caco2 cells. Antibiotic-induced dysbiosis is correlated with the enhancement in colonic tissue permeability, accompanied by a reduction in claudin 4 expression and enhancement in TNF-α and/or IFN-γ expression in mice. [ABSTRACT FROM AUTHOR]