Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China.
J Gastroenterol Hepatol. 2024 Apr;39(4):762-771. doi: 10.1111/jgh.16484. Epub 2024 Jan 17.
Patients with decompensated cirrhosis face poor prognosis and increased mortality risk. Rifaximin, a non-absorbable antibiotic, has been shown to have beneficial effects in preventing complications and improving survival in these patients. However, the underlying mechanisms of rifaximin's effects remain unclear.
We obtained fecal samples from decompensated cirrhotic patients undergoing rifaximin treatment and controls, both at baseline and after 6 months of treatment. Shotgun metagenome sequencing profiled the gut microbiome, and untargeted metabolomics analyzed fecal metabolites. Linear discriminant and partial least squares discrimination analyses were used to identify differing species and metabolites between rifaximin-treated patients and controls.
Forty-two patients were enrolled and divided into two groups (26 patients in the rifaximin group and 16 patients in the control group). The gut microbiome's beta diversity changed in the rifaximin group but remained unaffected in the control group. We observed 44 species with reduced abundance in the rifaximin group, including Streptococcus_salivarius, Streptococcus_vestibularis, Haemophilus_parainfluenzae, etc. compared to only four in the control group. Additionally, six species were enriched in the rifaximin group, including Eubacterium_sp._CAG:248, Prevotella_sp._CAG:604, etc., and 14 in the control group. Furthermore, rifaximin modulated different microbial functions compared to the control. Seventeen microbiome-related metabolites were altered due to rifaximin, while six were altered in the control group.
Our study revealed distinct microbiome-metabolite networks regulated by rifaximin intervention in patients with decompensated cirrhosis. These findings suggest that targeting these specific metabolites or related bacteria might be a potential therapeutic strategy for decompensated cirrhosis.
失代偿期肝硬化患者预后较差，死亡风险增加。利福昔明是一种不可吸收的抗生素，已被证明可预防并发症并改善这些患者的生存率。然而，利福昔明作用的潜在机制仍不清楚。
我们从接受利福昔明治疗和未接受治疗的失代偿期肝硬化患者中获得粪便样本，基线和治疗 6 个月后均进行了检测。 shotgun 宏基因组测序对肠道微生物组进行了分析，非靶向代谢组学分析了粪便代谢物。线性判别和偏最小二乘判别分析用于鉴定利福昔明治疗组和对照组患者之间不同的物种和代谢物。
共纳入 42 例患者，分为两组（利福昔明组 26 例，对照组 16 例）。利福昔明组的肠道微生物组β多样性发生了变化，而对照组则没有受到影响。与对照组相比，我们观察到利福昔明组有 44 个物种的丰度降低，包括链球菌_唾液链球菌、链球菌_vestibularis、流感嗜血杆菌等。此外，利福昔明组有 6 个物种富集，包括真细菌_ CAG:248、普雷沃氏菌_ CAG:604 等，对照组有 14 个物种富集。此外，利福昔明与对照组相比，调节了不同的微生物功能。由于利福昔明的作用，有 17 种微生物相关代谢物发生了变化，而对照组有 6 种代谢物发生了变化。
本研究揭示了利福昔明干预失代偿期肝硬化患者的独特肠道微生物群-代谢物网络。这些发现表明，针对这些特定的代谢物或相关细菌可能是治疗失代偿期肝硬化的一种潜在治疗策略。
