Lachnospiraceae strains alleviate IBS symptoms in mice via distinct gut-brain axis modulation

Irritable bowel syndrome (IBS) is a highly prevalent and debilitating disorder with limited effective treatments. Current approaches often target bowel dysfunction or central neuromodulators, but a significant gap remains in understanding the precise role of specific gut microbiota. Prior research linked the Lachnospiraceae family to IBS severity, yet conflicting data necessitated a deeper investigation into the heterogeneous mechanisms by which individual strains within this family might influence the gut-brain axis, visceral hypersensitivity, and intestinal barrier function.

Researchers evaluated four representative Lachnospiraceae strains in IBS mice with a standardized gut microbiota baseline (SynCom-23). Core IBS symptoms were assessed via body weight, fecal status, and visceral hypersensitivity. Intestinal inflammation, oxidative stress, and barrier function were quantified using ELISA and RT-qPCR. Gut microbiota and metabolites were analyzed by 16S rRNA sequencing, GC-FID, and LC-MS, alongside brain neurotransmitter systems. The study compared the effects of individual strains and a combined strain approach against control groups.

All four Lachnospiraceae strains effectively alleviated IBS symptoms in mice. They significantly reduced weight loss (P < 0.001) and markers of visceral hypersensitivity, specifically calcitonin gene-related peptide (CGRP) and transient receptor potential vanilloid 1 (TRPV1) (P < 0.0001). Each strain demonstrated distinct mechanistic pathways:

Blautia wexlerae MW-022 produced substantial acetic acid, stimulated Lactobacillaceae proliferation, and targeted the γ-aminobutyric acid/glutamate (GABA/Glu) system. Roseburia faecis MW-024 primarily produced butyrate, also affecting the GABA/Glu system. Dorea longicatena MW-023 enhanced the serotonin (5-HT) system at both synthesis and reception levels, while Coprococcus eutactus DSM107541 modulated the 5-HT system via a "clearance-reception" mode. Combined strains achieved more comprehensive gut micro-ecology restoration, suggesting synergistic effects.