肠道微生物群参与了利那洛肽治疗便秘型肠易激综合征（IBS-C）患者的疗效：一项多中心、前瞻性、前后研究。
The gut microbiota participates in the effect of linaclotide in patients with irritable bowel syndrome with constipation (IBS-C): a multicenter, prospective, pre-post study.
机构信息
Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037.
Department of Gastroenterology, The Ninth People's Hospital of Chongqing, No. 69 Jialing Village, Beibei District, Chongqing, China, 400700.
出版信息
J Transl Med. 2024 Jan 23;22(1):98. doi: 10.1186/s12967-024-04898-1.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
The gut microbiota, especially the genus Blautia, may serve as a significant predictive microbe for symptom relief in IBS-C patients receiving linaclotide treatment.
TRIAL REGISTRATION
This trial was registered with the Chinese Clinical Trial Registry (Chictr.org.cn, ChiCTR1900027934).
背景
Linaclotide 治疗后，便秘型肠易激综合征（IBS-C）患者的缓解程度存在个体差异。肠道微生物群与各种临床药物之间存在复杂的双向相互作用。迄今为止，尚无明确证据阐明肠道微生物群与 Linaclotide 之间的相互作用。我们旨在探讨 Linaclotide 对肠道微生物群的影响，并确定可能参与 Linaclotide 疗效的关键细菌属。
方法
IBS-C 患者接受 290µg 每日 Linaclotide 剂量治疗 6 周，然后在治疗后 4 周的观察期内记录症状。收集治疗前后粪便样本进行 16S rRNA 测序，以评估肠道微生物群组成的变化。此外，还进行靶向代谢组学分析以测量短链脂肪酸（SCFA）浓度。
结果
约 43.3%的患者在服用 Linaclotide 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。Linaclotide 显著改变了肠道微生物组和 SCFA 代谢。值得注意的是，Linaclotide 的更高疗效与 Blautia 属的富集相关，并且 Linaclotide 治疗后 Blautia 的丰度高于健康志愿者。有趣的是，在 IBS-C 患者中，Blautia 丰度与 SCFA 浓度与临床症状改善呈正相关。
结论
肠道微生物群，特别是 Blautia 属，可能是接受 Linaclotide 治疗的 IBS-C 患者症状缓解的重要预测微生物。
试验注册
该试验在中国临床试验注册中心（Chictr.org.cn，ChiCTR1900027934）注册。
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