The gut microbiota has been implicated in onset and progression of ulcerative colitis (UC). Here, we assess potential causal involvement of the microbiota and -associated fecal water (FW) metabolome in altering key functional parameters of the colonic epithelium. Fecal samples were collected from N = 51 healthy controls (HC), N = 36 patients with active UC (UC-A), and N = 41 subjects in remission N = 41 (UC-R). Using in vitro incubation experiments, the FW metabolome's impact on butyrate oxidation rates/gene expression and cell death (cytotoxicity) of HT-29 cells, cytokine production by PBMC, and barrier integrity of Caco2 monolayers was evaluated. The FW metabolome from patients and individuals hosting the Bacteroides 2 (Bact2) enterotype (69% of UC-A, 31% of UC-R, 3% of HC), characterized by lower levels of median- and short-chain fatty acids and furan compounds, left butyrate oxidation rates unaltered but affected associated gene expression profiles. UC patients/Bact2-carriers' FW lowered PBMC IL-8 production and increased IL-1β production. Patients' FW increased cytotoxicity, associated with sulfide compound levels. Bact2 carriers' FW, displaying higher levels of bile acids, lowered barrier function upon incubation of monolayers. The FW metabolome of patients and individuals hosting a dysbiotic microbiota could contribute to the disruption of functional processes of the colonic epithelium as observed in UC.

中文翻译：

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肠道微生物群和代谢组对溃疡性结肠炎病理机制的不同贡献：体外分析。


肠道菌群与溃疡性结肠炎 （UC） 的发病和进展有关。在这里，我们评估了微生物群和相关粪水 （FW） 代谢组在改变结肠上皮关键功能参数方面的潜在因果关系。从 N = 51 名健康对照者 （HC） 、N = 36 名活动性 UC （UC-A） 和 N = 41 名缓解期 N = 41 （UC-R） 受试者中收集粪便样本。使用体外孵育实验，评估了 FW 代谢组对 HT-29 细胞丁酸盐氧化速率/基因表达和细胞死亡（细胞毒性）、PBMC 产生细胞因子以及 Caco2 单层屏障完整性的影响。来自承载拟杆菌门 2 （Bact2） 肠型 （69% 的 UC-A、31% 的 UC-R、3% 的 HC） 的患者和个体的 FW 代谢组，其特征是中位和短链脂肪酸和呋喃化合物的水平较低，丁酸盐氧化速率未改变，但影响了相关的基因表达谱。UC 患者/Bact2 携带者的 FW 降低了 PBMC IL-8 的产生并增加了 IL-1β 的产生。患者的 FW 增加了与硫化物化合物水平相关的细胞毒性。Bact2 载体的 FW 显示更高水平的胆汁酸，在单层孵育时降低了屏障功能。正如在 UC 中观察到的那样，宿主菌群失调微生物群的患者和个体的 FW 代谢组可能导致结肠上皮功能过程的破坏。