粪便微生物移植治疗慢传输型便秘的疗效及其基于蛋白质消化吸收途径的相关机制。

BACKGROUND: Fecal microbiota transplantation (FMT) is considered an effective treatment for slow transit constipation (STC); nevertheless, the mechanism remains unclear. METHODS: In this study, eight patients with STC were selected according to the inclusion and exclusion criteria; they then received three treatments of FMT. The feces and serum of STC patients were collected after each treatment and analyzed by integrating 16 s rRNA microbiome and metabolomic analyses. RESULTS: The results showed that the percentage of clinical improvement reached 62.5% and the rates of patients' clinical remission achieved 75% after the third treatment. At the same time, FMT improved the Wexner constipation scale (WCS), the Gastrointestinal Quality-of-Life Index (GIQLI) and Hamilton Depression Scale (HAMD). Fecal microbiome alpha diversity and beta diversity altered significantly after FMT. Analysis of the 16 s rRNA microbiome showed that the numbers of Bacteroidetes (Prevotell/Bacteroides) and Firmicute (Roseburia/Blautia) decreased, whereas Actinobacteria (Bifidobacterium), Proteobacteria (Escherichia), and Firmicute (Lactobacillus) increased after FMT. The metabolomics analyses showed that the stool of FMT-treated patients were characterized by relatively high levels of N-Acetyl-L-glutamate, gamma-L-glutamyl-L-glutamic acid, Glycerophosphocholine, et al., after FMT. Compared with baseline, the serum of treated patients was characterized by relatively high levels of L-Arginine, L-Threonine, Ser-Arg, Indoleacrylic acid, Phe-Tyr, 5-L-Glutamyl-L-alanine, and lower levels of Erucamide after the treatment. The correlation analysis between the metabolites and gut microbiota showed a significant correlation. For example, L-Arginine was positively correlated with lactobacillus, et al. L-Threonine was positively correlated with Anaerovibrio, Sediminibacterium but negatively correlated with Phascolarctobacterium. Erucamide had significant negative correlations with Sediminibacterium and Sharpea, while being positively correlated with Phascolarctobacterium. Enriched KEGG pathways analysis demonstrated that the protein digestion and absorption pathways gradually upregulated with the increase of FMT frequency. The L-Arginine and L-Threonine were also involved in the pathway. A large amount of Na + was absorbed in the pathway, so that it might increase mucus secretion and electrical excitability of GI smooth muscle. CONCLUSIONS: Therefore, we speculated that FMT changed the patients' gut microbiota and metabolites involved in the protein digestion and absorption pathways, thereby improving the symptoms of STC. Study on the effectiveness and safety of FMT in the treatment of STC. The study was reviewed and approved by Ethics Committee of Tianjin People's Hospital (ChiCTR2000033227) in 2020.

背景：粪便微生物群移植（FMT）被认为是治疗慢传输型便秘（STC）的有效方法；然而，其机制仍不清楚。

方法：本研究根据纳入和排除标准选择了 8 例 STC 患者，他们接受了 3 次 FMT 治疗。在每次治疗后收集 STC 患者的粪便和血清，并通过整合 16s rRNA 微生物组和代谢组学分析进行分析。

结果：结果显示，第三次治疗后临床改善率达到 62.5%，临床缓解率达到 75%。同时，FMT 改善了 Wexner 便秘量表（WCS）、胃肠道生活质量指数（GIQLI）和汉密尔顿抑郁量表（HAMD）。FMT 后粪便微生物组 α多样性和 β多样性明显改变。16s rRNA 微生物组分析显示，FMT 后拟杆菌/双歧杆菌和厚壁菌门（Roseburia/Blautia）数量减少，而放线菌（双歧杆菌）、变形菌（埃希氏菌）和厚壁菌门（乳杆菌）数量增加。代谢组学分析表明，FMT 治疗后患者的粪便以 N-乙酰-L-谷氨酸、γ-L-谷氨酰-L-谷氨酸、甘油磷酸胆碱等水平较高为特征。与基线相比，治疗后患者的血清以 L-精氨酸、L-苏氨酸、丝氨酸-精氨酸、吲哚丙烯酸、苯丙氨酸-酪氨酸、5-L-谷氨酰-L-丙氨酸水平较高，而神经酰胺水平较低。代谢物与肠道微生物群的相关性分析表明，两者之间存在显著相关性。例如，L-精氨酸与乳杆菌等呈正相关。L-苏氨酸与 Anaerovibrio、Sediminibacterium 呈正相关，与 Phascolarctobacterium 呈负相关。神经酰胺与 Sediminibacterium 和 Sharpea 呈显著负相关，与 Phascolarctobacterium 呈正相关。富集的 KEGG 通路分析表明，蛋白消化吸收途径随着 FMT 频率的增加逐渐上调。L-精氨酸和 L-苏氨酸也参与了该途径。该途径中大量吸收 Na+，可能会增加 GI 平滑肌的黏液分泌和电兴奋性。

结论：因此，我们推测 FMT 改变了患者参与蛋白消化吸收途径的肠道微生物群和代谢物，从而改善了 STC 的症状。研究 FMT 治疗 STC 的有效性和安全性。本研究于 2020 年经天津市人民医院伦理委员会（ChiCTR2000033227）审查和批准。