RESUMO
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).
Assuntos
Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Peptídeos , Humanos , Estudos Prospectivos , RNA Ribossômico 16S , Constipação IntestinalRESUMO
Supramolecular gels, a fascinating class of soft materials, are of great interest for their wide applications. In this work, a series of organic gelators derived from phenyllactic acid were prepared, and their gelation properties were further investigated. It was found that the gelator 1e bearing a hydrazine moiety could congeal 17 kinds of common organic liquids (polar and non-polar) efficiently. Meanwhile, the morphological structures and dominant factors of the gel were examined by scanning electron microscope (SEM), transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), concentration and temperature-dependent 1H NMR. Crucially, the gelator displayed outstanding performances in toxic phenol removal and spilled oil and petroleum products recovery. Moreover, it also displayed a satisfactory recyclability, which will greatly promote its application in practice. These impressive results will provide a novel avenue for the water treatment and the development of functional supramolecular gel materials.