Phylogenetic and Comparative Genomic Analysis of Lactobacillus fermentum Strains and the Key Genes Related to their Intestinal Anti-Inflammatory Effects

Abstract

• Pan-genomic and phylogenetic characterizations of 109 L. fermentum strains. • Evolution of L. fermentum lineages was not associated with geographical location. • Immunomodulatory properties of L. fermentum were strain-dependent. • Candidate genes that may account for the anti-inflammatory effects were identified. Emerging evidence shows that some Lactobacillus fermentum strains can contribute to the prevention and treatment of ulcerative colitis (UC). In this study, 105 isolates of L. fermentum strains were separated from fecal samples of populations in different regions in China and their draft genomes were sequenced. Pan-genomic and phylogenetic characterizations of these strains and four model strains ( L. fermentum 3872, CECT5716, IFO3956 and VRI003) were performed. Phylogenetic analysis indicated that there was no significant adaptive evolution between the genomes of L. fermentum strains and the geographical location, sex, ethnicity and age of the hosts. Three L. fermentum strains (FWXBH115, FGDLZR121, and FXJCJ61) from different branches of the phylogenetic tree and strain type L. fermentum CECT5716 were selected and their anti-inflammatory and immune modulatory activities in a dextran sulphate sodium (DSS)-induced colitis mouse model were further investigated. Both L. fermentum FXJCJ61 and CECT5716 significantly alleviated UC by reducing all colitis-associated histological indices, maintaining mucosal integrity, and stimulating replenishment of short-chain fatty acids (SCFAs), while the other two strains failed to offer similar protection. The anti-inflammatory mechanisms of L. fermentum FXJCJ61 and CECT5716 were related to the inhibition of nuclear factor kappa-B (NF-κB) signaling pathway activation and enhancement of interleukin 10 (IL-10) production. Comparative genomic analysis of these strains identified candidate genes that may contribute to the anti-inflammatory effects of specific L. fermentum strains.