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

Abstract

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).

Short-chain Fatty Acids and Human Health: from Metabolic Pathways to Current Therapeutic Implication

“…Zhou et al recently set out to investigate how linaclotide affects the gut microbiota and pinpoint essential bacterial genera that could influence linaclotide's effectiveness. Interestingly, they discovered a direct link between higher levels of Blautia and SCFA concentrations and the amelioration of clinical symptoms in patients with IBS-C [259].…”

Short-Chain Fatty Acids and Human Health: From Metabolic Pathways to Current Therapeutic Implications

“…Zhou et al, recently set out to investigate how linaclotide affects the gut microbiota and pinpointed essential bacterial genera that could influence linaclotide's effectiveness. Interestingly, they discovered a direct link between higher levels of Blautia and SCFAs concentrations and the amelioration of clinical symptoms in patients with IBS-C [245].…”