Functional Equivalence of Heat-Inactivated (HI) and Live Probiotic RSB11 in Suppressing Inflammation: Expanding Formulation and Application Potential

The clinical potential of probiotics has been widely recognized, but their translation into reliable therapeutic products has been hindered by major limitations such as undesirable immunogenic responses, the need to maintain viability, instability during storage and transport, and concerns regarding safety in vulnerable populations. Postbiotics, defined as inanimate microbial cells or their components with pro-health activities, overcome many of these limitations by offering enhanced stability, reproducibility, and safety. However, it is very vital to understand if the heat inactivation (conversion of a probiotic to its postbiotic inert form) compromise its functional efficacy. Here, we systematically compared a novel probiotic-derived candidate, <i>Lactiplantibacillus plantarum</i> RSB11 strain, in its live (RSB11 Life, probiotic) and heat-inactivated (RSB11-HI, postbiotic) forms across multiple human epithelial and non-epithelial models relevant to inflammation driven pathologies. To investigate the gut-tissue(s)-axis concept we used gut (Caco-2), lung (HBE), ovary (BG1), bone (osteoblasts, MG-63), kidney (A-498) and liver (HepG2) cells exposed to <i>E-coli</i> or lipopolysaccharide (LPS), and quantified matrix metalloproteinase-9 (MMP-9), an inflammatory mediator, by qPCR and pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), IL-6, and IL-1β by ELISA. In addition, we assessed β-glucuronidase activity and estrogen modulation to explore gut-ovarian axis signaling. Across all models, both RSB11 Life and RSB11-HI robustly suppressed MMP-9, TNF-α, IL-6 and IL-1β induction, with equivalent magnitude of effect. The inactivated form retained full cytokine-suppressive capacity and, notably, enhanced β-glucuronidase activity, suggesting additional benefits in microbiome hormone cross-talk. Our findings demonstrate that heat inactivation does not compromise, and may even expand, the functional range of RSB11. By maintaining bioactivity while eliminating the drawbacks of live biotics, heat inactivated RSB11 emerges as a robust, scalable, and versatile postbiotic with potential applications in systemic inflammatory disorders.