WGS analysis and functional studies illustrate promising gene-signatures for probiotic attributes and molecular-targeted therapeutic prospects of Lactiplantibacillus plantarum LP-ARP2.

Gene-signatures for probiotic attributes expedite screening of novel probiotic strains as well as identify molecular basis of probiotic benefits. Therefore, strain-specific genomic-studies correlating functional-assays are in demand. Here, we present the same for Lactiplantibacillus plantarum LP-ARP2 using genomic-metabolomic-functional approaches. Genomic-features of LP-ARP2 are further compared with clinically relevant L. plantarum strains to elucidate gene-specific commonality. We find robust stress-resilience genetic set-up (usp/hsl/clp/ABC-transporters/ ATP-synthase/chaperons dna/gro/grp) in LP-ARP2-genome. Our acid/bile tolerance assays also indicate survivability (> 60%) of the strain in harsh conditions. Presence of adhesion-related (lspA/mapA/eno/srtA/glycosyltransferases/glycosylhydrolases/lipoproteins) and biofilm-forming genes (veg/luxS) further align with its efficacy in autoaggregation (> 60%), adhesion (Caco-2), and biofilm-formation (24 h). CAZyme-genes with significant prebiotic utilization indicate the strain's ability for gut-microbial-modulation and adaptation. Metabolic-profiling of LP-ARP2-derived-CFS (HRMS analysis) validates the presence of related genes for SCFAs/vitamins/amino-acids/neurotransmitters GABA/serotonin/acetylcholine etc. Besides, many metabolites are reported antimicrobials. Indeed LP-ARP2 shows significant antibacterial potential against multidrug-resistant bacteria (Gram-positive/Gram-negative), gut-pathogen Salmonella Typhimurium and pathogenic-biofilm (MRSA). Presence of antioxidant-genes in LP-ARP2-genome (thioredoxin/NADH-dependent-nox/npr/ndh/glutathione-reductase/glutaredoxin/catalase/peroxidases/methionine sulfoxide reductase) are validated by high radical-scavenging activity of LP-ARP2 (ABTS > 40%, DPPH 25 U/mL, superoxide > 80%, and hydroxyl > 70%). Moreover, in-silico functional-network-analysis reveals LP-ARP2-derived metabolites target oxidative stress, neuroinflammation, amyloid-beta metabolism, tau-phosphorylation, neurogenesis, and synaptic function, indicating molecular relevance of the therapeutic potential of LP-ARP2. Fascinatingly, genomic-analysis between LP-ARP2 with clinically relevant (depression and intestinal disorders) L. plantarum strains (299v and Lp01) elucidate comparable genetic-features for beneficial probiotics. Thus, study offers potential gene-signatures for probiotic-benefits of L. plantarum and project LP-ARP2 as a promising probiotic with antibacterial, antioxidant and psychobiotic potential.