Comparative genomics reveals immunomodulatory and anti-obesity traits of Lactococcus lactis subsp. lactis

Lactococcus lactis subsp. lactis strains have been widely recognized for their probiotic potential, including their immunomodulatory and anti-obesity effects. This study aims to determine the genomic basis of the health-promoting properties of L. lactis subsp. lactis CAB701 and WiKim0124 using whole-genome sequencing and comparative genomic analysis. Taxonomic classification using average nucleotide identity and digital DNA-DNA hybridization confirms both strains as L. lactis subsp. lactis. Genome alignment reveals high synteny among CAB701, WiKim0124, and the reference strains, with minor structural variations. Functional annotation identifies genes associated with carbohydrate metabolism, biofilm formation, and immune modulation. Pan-genome analysis shows a substantial proportion of strain-specific genes, suggesting niche-specific adaptation. Notably, L. lactis subsp. lactis CAB701 and WiKim0124 harbor unique biosynthetic gene clusters for nisin Z and sactipeptides, which may contribute to their antimicrobial and immunomodulatory functions. Additionally, genes involved in short-chain fatty acid metabolism are identified, highlighting their potential role in metabolic regulation. These findings provide valuable insights into the functional genetics of L. lactis subsp. lactis and their applicability as probiotics for immune modulation and obesity management. KEY POINTS: • Comparative genomics revealed strain-specific immune- and metabolism-linked genes • CAB701 and WiKim0124 uniquely harbor nisin Z and sactipeptide biosynthetic clusters • Genomic features support L. lactis application as functional probiotics.