Staunch the Age Related Decline into Depression, Dementia, Diabetes, Obesity, Cancer, Long Covid, and Other Diseases with a Prebiotic, Probiotic, Postbiotic Triple Play

Abstract

“All diseases originate in the gut.” Hippocrates (400 BC) A healthy gut microbiome via the gut-brain-axis (GBA) elevates heart rate variability (HRV), a general measure of health and well-being. A dysbiotic gut microbiome, low in biodiversity and butyrate producers, triggers altered tryptophan metabolism and release of proinflammatory cytokines, predominantly TNF-α, IL-6, and IL-1β, that also characterize chronic inflammation, oxidative stress, and a multitude of diseases, all exhibiting low HRV. Gut dysbiosis upregulates IFN-γ and with it IDO (indoleamine 2,3 dioxygenase). Tryptophan pivots from serotonin synthesis to that of kynurenine, increasing the kynurenine to tryptophan ratio (KTR). An elevated KTR is positively linked to neurodegenerative and autoimmune diseases and negatively linked to HRV. Elevated IDO activity is not only enzymatic but also an intracellular signal transducer potentiated by TGF-β. This cytokine is the primary determinant of the TME. The triple play of a prebiotic (d-mannose), probiotic (bifidobacteria and lactobacilli), and postbiotic (butyrate) might improve intestinal barrier integrity, suppress the inflammatory cytokine triad, balance IFN-γ and TGF-β, depress KTR, elevate HRV, and extend lifespan.