Fecal microbiota transplantation ameliorates experimental colitis via gut microbiota and T-cell modulation

Summary: Cepharanthine (CEP) is an active alkaloid isolated from Stephania Cepharantha Hayata. It is reported that the anti‐inflammatory properties of CEP could be employed to treat a variety of diseases. In this study, we first found that CEP ameliorates ulcerative colitis (UC) induced by DSS. The effect of CEP on gut microbiota was further evaluated by 16S rRNA gene sequencing, antibiotic pretreatment and faecal microbiota transplantation (FMT). Results showed that the abundances of gut microbiota, such as Romboutsia , Turicibacter and Escherichia‐Shigella (especially Romboutsia ), were significantly reduced after CEP treatment. Additionally, we explored the mechanisms of CEP by a strategy integrating transcriptomics with network pharmacology. The transcriptome data confirmed that CEP functioned through cytokine and cytokine receptor pathways. The expression levels of 10 pro‐inflammatory hub genes (such as CXCL1, CXCL9, CCL7) were positively correlated with the abundance of Romboutsia . Our data identified Romboutsia as a potential pathobiont in UC. Collectively, we confirmed that CEP relieved colon inflammation by modulating gut microbiota and pro‐inflammatory cytokine expression. CEP can be adopted to design novel effective therapeutic strategies for UC.

Growing evidence supports the efficacy and safety of fecal microbiota transplantation (FMT) in treating Parkinson's disease (PD). Fecal microbiota are commonly transplanted via oral capsules, a nasojejunal tube, or colonoscopy, but freezing often decreases the diversity and viability of transplanted microbiota. This single-center, double-blind, randomized, placebo-controlled trial aims to explore the efficacy and safety of fresh FMT via colonoscopy in dealing with PD. Thirty patients with mild-to-moderate PD (Hoehn-Yahr stage I-III) were randomly assigned into the FMT group (fresh FMT via colonoscopy) and placebo group (saline injection via colonoscopy) in a 1:1 ratio. Motor and non-motor symptoms, constipation, quality of life, cognitive function, emotional state and sleep quality were assessed using relevant scales. Fecal samples were harvested before and at 4, 8 and 12 weeks after treatment for metagenomic and metabolomics analyses. A total of 30 patients with mild-to-moderate PD were enrolled in the present study, involving 18 males and 12 females with a median age of 68 years, a median age of onset of 63.5 years, and a median disease duration of 3 years. At 12 weeks, scores of the UPDRS Ⅲ (group × time effect, B = - 8.80 [-13.79, -3.81]), PAC-QOL (group × time effect, B = - 29.67 [-45.35, -13.98]), UPDRS Ⅱ (group × time effect, B = - 5.07 [-8.85, -1.28]), NMSS (group × time effect, B = - 35.60 [-53.59, -17.61]), PDQ-39 (group × time effect, B = - 17.80 [-28.21, -7.39]), HAMA (group × time effect, B = - 1.66 [-2.92, -0.40]), and HAMD (group × time effect, B = - 1.33 [-2.49, -0.16]) were significantly reduced in the FMT group, while CSBM per week (group × time effect, B = 3.03 [1.42, 4.63]) and the Bristol Stool Scale score (group × time effect, B = 1.95 [0.12, 3.79]) significantly increased (all P < 0.05). Significant alterations were seen in the gut microbiota and fecal metabolites in the FMT group. No adverse events were observed during the follow-up period. Fresh FMT via colonoscopy is a safe and well-tolerated procedure for treating mild-to-moderate PD. It effectively alleviates motor and non-motor symptoms, thus facilitating defecation and improving the quality of life. These effects can be maintained for a minimum of 12 weeks and may be attributed to the optimization of gut microbiota and fecal metabolites.