背景:个体差异表征了利那洛肽治疗后便秘型肠易激综合征(IBS-C)患者的缓解。在肠道微生物群和各种临床药物之间发生复杂的双向相互作用。迄今为止,没有确凿的证据阐明肠道微生物群和利那洛肽之间的相互作用。我们旨在探索利那洛肽对肠道微生物群的影响,并确定可能参与利那洛肽功效的关键细菌属。
方法:IBS-C患者在六周内每天服用290µg的利那洛肽,然后在治疗后4周的观察期内记录他们的症状.收集治疗前和治疗后的粪便样品进行16SrRNA测序,以评估肠道微生物组成的变化。此外,对短链脂肪酸(SCFA)浓度进行靶向代谢组学分析.
结果:大约43.3%的患者在服用利那洛肽6周后达到FDA应答终点,85%的患者报告腹痛和便秘有所缓解。利那洛肽显著改变了肠道微生物组和SCFA代谢。值得注意的是,利那洛肽的较高功效与布劳特氏菌属的富集有关,利那洛肽治疗后布劳特氏菌的丰度高于健康志愿者。有趣的是,在IBS-C患者中,Blautia丰度和SCFA浓度与临床症状改善呈正相关.
结论:肠道菌群,尤其是布劳特属,在接受利那洛肽治疗的IBS-C患者中,可能是症状缓解的重要预测微生物。
背景:该试验已在中国临床试验注册中心(Chictr.org。cn,ChiCTR1900027934)。
Interindividual variation characterizes the relief experienced by constipation-predominant irritable bowel syndrome (IBS-C) patients following linaclotide treatment. Complex bidirectional interactions occur between the gut microbiota and various clinical drugs. To date, no established evidence has elucidated the interactions between the gut microbiota and linaclotide. We aimed to explore the impact of linaclotide on the gut microbiota and identify critical bacterial genera that might participate in linaclotide efficacy.
IBS-C patients were administered a daily linaclotide dose of 290 µg over six weeks, and their symptoms were then recorded during a four-week posttreatment observational period. Pre- and posttreatment fecal samples were collected for 16S rRNA sequencing to assess alterations in the gut microbiota composition. Additionally, targeted metabolomics analysis was performed for the measurement of short-chain fatty acid (SCFA) concentrations.
Approximately 43.3% of patients met the FDA responder endpoint after taking linaclotide for 6 weeks, and 85% of patients reported some relief from abdominal pain and constipation. Linaclotide considerably modified the gut microbiome and SCFA metabolism. Notably, the higher efficacy of linaclotide was associated with enrichment of the
Blautia genus, and the abundance of
Blautia after linaclotide treatment was higher than that in healthy volunteers. Intriguingly, a positive correlation was found for the
Blautia abundance and SCFA concentrations with improvements in clinical symptoms among IBS-C patients.
The gut microbiota, especially the genus
Blautia, may serve as a significant predictive microbe for symptom relief in IBS-C patients receiving linaclotide treatment.
This trial was registered with the Chinese Clinical Trial Registry (Chictr.org.cn, ChiCTR1900027934).