జర్నల్ ఆఫ్ మైక్రోబియల్ & బయోకెమికల్ టెక్నాలజీ

నైరూప్య

Ferulic Acid Produced by Lactobacillus fermentum NCIMB 5221 Reduces Symptoms of Metabolic Syndrome in Drosophila melanogaster

Susan Westfall, Nikita Lomis, Surya Pratap Singh and Satya Prakash

Abstract

The gut microbiota is an intricate community of thousands of bacterial species living in the gastrointestinal tract critical for vitamin synthesis, mineral absorption, digestion of otherwise indigestible fibers and the extraction of energy from food. Recently, the health of the gut microbiota’s community architecture has become linked to energy-regulatory diseases including metabolic syndrome: a collection of symptoms including hyperglycemia, hypercholesterolemia, high blood pressure, increased abdominal fat and triglyceride levels. However, the mechanism of communication between the gut microbiota and the host energy metabolism remains elusive. The current study shows that ferulic acid (FA) produced by the intrinsic ferulic acid esterase activity of the probiotic bacteria Lactobacillus fermentum NCIMB 5221 (Lf5221) can dose-dependently rescue the phenotypic markers of diet-induced diabetes and obesity in Drosophila melanogaster. In Drosophila exposed to either a high-sugar or high-fat diet, living Lf5221 at 2.5 or 7.5 × 109 CFU/ml media effectively rescued whole-body weight, glucose, trehalose and triglyceride levels. All of the aforementioned effects were lost in heat-inactivated bacteria indicating that a metabolic product is responsible. Likewise, FA at 0.5 mM in the metabolically challenged Drosophila models reared similar effects on the physiological markers while also reducing hyperglycemia in the circulating hemolymph. On the signaling level, the high-sugar diet predictably had elevated expression of the Drosophila insulin-like peptides 2, 3 and 5 and in the high-fat diet, an increase in fatty acid synthase, acetyl-CoA carboxylase and phosphoenolpyruvate carboxykinase expression. On both diets, Lf5221 and FA rescued gene expression, at different concentrations, to the level of controls. Examining the mechanistic gene expression, both Lf5221 and FA rescued expression of dFOXO and dTOR, but not dAkt indicating that FA produced by Lf5221 is acting on one of the downstream-signaling molecules from the insulin receptor, possibly dTOR: an overall energy regulator in flies and humans alike. The present study for the first time outlines a streamlined mechanism for how the gut microbiota communicates with the host’s energy-regulating metabolism. Proper supplementation with ferulic acid esterase active probiotics such as Lf5221 could potentially prevent or alleviate symptoms of metabolic syndrome and other energy-regulating diseases including diabetes, obesity and neurodegeneration.