Lactiplantibacillus plantarum: Systems Biology of a Versatile Microbe.

Lactiplantibacillus plantarum is a metabolically versatile lactic acid bacterium found in fermented foods and the human gastrointestinal tract. Its relatively large genome (3.0-3.6 Mb) features an open pan-genome with 1,436-2,100 core genes and over 13,000 cloud genes, enabling remarkable adaptation to diverse environments. This species encodes a diverse repertoire of CAZymes that degrade plant polysaccharides and host glycans, yielding short-chain fatty acids that modulate epithelial barrier integrity, host metabolism, and immune signaling. Pattern-recognition receptors (PRRs, including TLR2, TLR9, and NOD2) detect L. plantarum at the host interface, primarily through cell-surface molecules such as lipoteichoic acids, peptidoglycan, and exopolysaccharides. These interactions can influence NF-κB signaling, leading to either inflammatory or regulatory responses, depending on the specific strain. Certain strains also possess the glutamate decarboxylase system (GadB/GadC), which transforms dietary glutamate into gamma-aminobutyric acid (GABA), linking L. plantarum to the biology of the gut-brain axis. Despite substantial mechanistic evidence, clinical outcomes are inconsistent due to the significant variability among strains, marked differences in host microbiomes, and the absence of predictive multiomic markers for colonization and efficacy. This review consolidates current insights on genome organization, metabolic characteristics, and mechanisms of host interaction, with a specific focus on the challenges that continue to hinder the advancement of L. plantarum as a precision biotherapeutic.