Probiotic induced synthesis of microbiota polyamine as a nutraceutical for metabolic syndrome and obesity-related type 2 diabetes

Abstract

The gut microbiota regulates multiple facets of host metabolism and immunity through the production of signaling metabolites, such as polyamines which are small organic compounds that are essential to host cell growth and lymphocyte activation. Polyamines are most abundant in the intestinal lumen, where their synthesis by the gut microbiota is influenced by microbiome composition and host diet. Disruption of the host gut microbiome in metabolic syndrome and obesity-related type 2 diabetes (obesity/T2D) results in potential dysregulation of polyamine synthesis. A growing body of evidence suggests that restoration of the dysbiotic gut microbiota and polyamine synthesis is effective in ameliorating metabolic syndrome and strengthening the impaired immune responses of obesity/T2D. In this review, we discuss existing studies on gut microbiome determinants of polyamine synthesis, polyamine production in obesity/T2D, and evidence that demonstrates the potential of polyamines as a nutraceutical in obesity/T2D hosts.

Keywords: metabolic syndrome; nutraceutical; obesity; polyamine; type 2 diabetes.

Figure 1

Distribution of natural polyamines in healthy adults. The three most abundant polyamines in humans are putrescine, spermidine, and spermine. Total polyamine is highest in the intestine because diet and gut microbiome are the primary sources of polyamines. From the gastrointestinal tract, polyamines are readily absorbed and enter circulation where they are found in a variety of organs including the brain, kidneys, and in metabolic fluids such as urine, and breastmilk. Studies that reported concentrations in ng/mL or μg/mL were transformed to μM using the molecular weights of putrescine (88.15 g/mol), spermidine (145.25 g/mol), and spermine (202.34 g/mol) for better comparisons.

Figure 2

Proposed health benefits of dietary polyamines in obesity-related diseases. Polyamines are essential to human health, with their abundance altered by obesity-related diseases. This figure highlights a summary of potential benefits of polyamines on obesity-related diseases including metabolic syndrome and type 2 diabetes. Polyamines ameliorate metabolic syndrome by reducing weight gain, insulin resistance, lipid metabolism, gut barrier function, and metabolic endotoxemia. Polyamines also regulate both innate and adaptive immunity including proinflammatory cytokine production, autophagy, macrophage polarization, T cell differentiation, and B cell senescence. Further investigation is needed to elucidate polyamine-mediated health benefits in obesity-related diseases.