Novel identified Faecalibacterium prausnitzii metabolites fortify the intestinal barrier: A multi-omics study

Revealing strain-level diversity in the gut microbiome is critical to understanding its impact on health. Genomic and metabolomic advances enable strain-level dissection of the gut microbiome. Faecalibacterium prausnitzii , a prevalent commensal bacterium in the human gut, is a promising candidate for next-generation probiotics. However, the study on genomic and metabolomic diversity of F. prausnitzii strains remains insufficient. In this study, 12 F. prausnitzii strains were isolated and whole genome sequencing was conducted. Results showed that these strains were classified into three phylogenetic clades (clade B, C, and D). Additionally, strain FP3003 displayed typical characteristics, marked by significant acetate consumption and butyrate production. Further integration of non-targeted metabolomics analysis and an in vitro intestinal epithelial cell model confirmed the established intestinal protective effects of F. prausnitzii and butyrate. Moreover, we identified four novel beneficial F. prausnitzii -derived metabolites, including indolelactic acid (ILA), hydroxyphenyllactic acid, hydroxyisocaproic acid, and butoxyacetic acid, among which ILA upregulated Occludin and Ecadherin expression in vitro . In summary, our results systematically elucidated the strain-level insights into the metabolic diversity and functional heterogeneity of F. prausnitzii . This study expanded the current knowledge on F. prausnitzii and established a key research paradigm for investigating the functional potential of next-generation probiotics.