A Defined Synbiotic Produces Immunomodulatory Metabolites, Engages Gut-Immune Pathways Relevant to Inflammaging, and...

Chronic low-grade aging-associated inflammation, or inflammaging, is a central pillar of age-related decline in quality of life. Inflammaging is partially mediated by impaired intestinal, immune, and microbiome function, and it has been hypothesized that probiotics could be used to promote healthy aging. SBD121, a defined synbiotic containing food-derived microbial strains and prebiotic fibers, has previously been shown to improve grip strength in male rats, an important indicator of healthspan, and is under evaluation in a clinical trial of 143 newly diagnosed rheumatoid arthritis patients (NCT06005220). However, the mechanisms underlying its potential benefits have not been determined. Here, we examined the function of SBD121 in microbial, cellular, and animal models relevant to inflammaging. SBD121 inhibited the growth of potential microbial pathogens, produced immunomodulatory metabolites in vitro, and improved human intestinal cell barrier function under both basal and challenge conditions, while reducing inflammatory chemokine secretion following inflammatory challenge. SBD121 also reduced the secretion of multiple chemokines in lipopolysaccharide-stimulated human intestinal and immune cells. Finally, SBD121 improved survival and locomotor activity in a C. elegans longevity model, providing evidence of benefits to lifespan and healthspan. Together, these data demonstrate that SBD121 exhibits beneficial microbial, epithelial, immune, and longevity effects and support continued investigation of SBD121 as a candidate intervention for healthy aging.