Therapeutic potential of Lachnospiraceae strains in irritable bowel syndrome via differential gut-brain pathways

Background: Irritable bowel syndrome (IBS) is a highly prevalent disorder that significantly impairs quality of life, yet effective treatments remain limited. While prior work from our laboratory linked the Lachnospiraceae family to IBS severity, conflicting sequencing data necessitated a deeper investigation into this taxonomic group. Methods: We evaluated the therapeutic potential of four representative Lachnospiraceae strains in IBS mice with standardized gut microbiota baseline (SynCom-23). Core symptoms were assessed via body weight, fecal status, and visceral hypersensitivity. Intestinal inflammation, oxidative stress, and barrier function were evaluated by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (RT-qPCR), and gut microbiota and metabolites were analyzed by 16S rRNA sequencing, gas chromatography-flame ionization detector (GC-FID), and liquid chromatography-mass spectrometry (LC-MS), together with brain neurotransmitter systems. Results: We found that all four strains effectively alleviated IBS symptoms, reducing weight loss (P < 0.001) and visceral hypersensitivity markers calcitonin gene-related peptide (CGRP) and transient receptor potential vanilloid 1 (TRPV1) (P < 0.0001), potentially through distinct pathways: Blautia wexlerae MW-022 produces substantial acetic acid, stimulates Lactobacillaceae proliferation, and targets the γ-aminobutyric acid/glutamate (GABA/Glu) system. Roseburia faecis MW-024 produces butyrate, affecting the GABA/Glu system. Dorea longicatena MW-023 enhances the serotonin (5-HT) system at synthesis and reception levels; and Coprococcus eutactus DSM107541 modulates the 5-HT system via the “clearance-reception” mode. Combined strains achieved more comprehensive gut micro-ecology restoration. Conclusion: This study systematically elucidates the heterogeneity in the mechanisms by which Lachnospiraceae strains treat IBS at the strain level. Different strains achieve precise regulation through their specific gut-brain axes. These findings offer strain-level insights and a foundation for developing Lachnospiraceae-based microbial therapies.