Fecal Coprococcus, hidden behind abdominal symptoms in patients with small intestinal bacterial overgrowth.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is the presence of an abnormally excessive amount of bacterial colonization in the small bowel. Hydrogen and methane breath test has been widely applied as a non-invasive method for SIBO. However, the positive breath test representative of bacterial overgrowth could also be detected in asymptomatic individuals. METHODS: To explore the relationship between clinical symptoms and gut dysbiosis, and find potential fecal biomarkers for SIBO, we compared the microbial profiles between SIBO subjects with positive breath test but without abdominal symptoms (PBT) and healthy controls (HC) using 16S rRNA amplicon sequencing. RESULTS: Fecal samples were collected from 63 SIBO who complained of diarrhea, distension, constipation, or abdominal pain, 36 PBT, and 55 HC. For alpha diversity, the Shannon index of community diversity on the genus level showed a tendency for a slight increase in SIBO, while the Shannon index on the predicted function was significantly decreased in SIBO. On the genus level, significantly decreased Bacteroides, increased Coprococcus_2, and unique Butyrivibrio were observed in SIBO. There was a significant positive correlation between saccharolytic Coprococcus_2 and the severity of abdominal symptoms. Differently, the unique Veillonella in the PBT group was related to amino acid fermentation. Interestingly, the co-occurrence network density of PBT was larger than SIBO, which indicates a complicated interaction of genera. Coprococcus_2 showed one of the largest betweenness centrality in both SIBO and PBT microbiota networks. Pathway analysis based on the Kyoto Encyclopedia of Genes and Genome (KEGG) database reflected that one carbon pool by folate and multiple amino acid metabolism were significantly down in SIBO. CONCLUSIONS: This study provides valuable insights into the fecal microbiota composition and predicted metabolic functional changes in patients with SIBO. Butyrivibrio and Coprococcus_2, both renowned for their role in carbohydrate fermenters and gas production, contributed significantly to the symptoms of the patients. Coprococcus's abundance hints at its use as a SIBO marker. Asymptomatic PBT individuals show a different microbiome, rich in Veillonella. PBT's complex microbial interactions might stabilize the intestinal ecosystem, but further study is needed due to the core microbiota similarities with SIBO. Predicted folate and amino acid metabolism reductions in SIBO merit additional validation.

Berberine and rifaximin effects on small intestinal bacterial overgrowth: Study protocol for an investigator-initiated, double-arm, open-label, randomized clinical trial (BRIEF-SIBO study).

Introduction: Small intestinal bacterial overgrowth (SIBO) leads to non-specific abdominal discomfort and nutrient malabsorption. Currently, rifaximin is widely applied in SIBO based on its antibacterial and non-absorbable nature. Berberine is a natural component of many popular medicine plants that ameliorates intestinal inflammation in humans through its modification of the gut microbiota. Potential effect of berberine to the gut may provide therapeutic target for SIBO. We aimed to evaluate the effect of berberine compared with rifaximin on SIBO patients. Methods: This is an investigator-initiated, single-center, open-label, double-arm randomized controlled trial, termed BRIEF-SIBO (Berberine and rifaximin effects for small intestinal bacterial overgrowth). In total, 180 patients will be recruited and allocated to an intervention group (berberine) and a control group (rifaximin). Each participant will receive one 400 mg drug twice a day (800 mg daily) for 2 weeks. The total follow-up period is 6 weeks from the start of medication. The primary outcome is a negative breath test. The secondary outcomes include abdominal symptom relief and alteration in gut microbiota. Efficacy assessment will be performed every 2 weeks, as well as safety assessment during the treatment. The primary hypothesis is that berberine is not inferior to rifaximin for SIBO. Discussion: The BRIEF-SIBO study is the first clinical trial assessing the eradication effects of 2 weeks of berberine treatment in SIBO patients. The effect of berberine will be fully verified by using rifaximin as the positive control. The findings of this study may have implications for the management of SIBO, especially increasing the awareness of both physicians and patients who are suffering from long-term abdominal discomfort and avoiding excessive examination.