Leuconostoc mesenteroides mediates an electrogenic pathway to attenuate the accumulation of abdominal fat mass induced by high fat diet.

Although several electrogenic bacteria have been identified, the physiological effect of electricity generated by bacteria on host health remains elusive. We found that probiotic Leuconostoc mesenteroides (L. mesenteroides) can metabolize linoleic acid to yield electricity via an intracellular cyclophilin A-dependent pathway. Inhibition of cyclophilin A significantly abolished bacterial electricity and lowered the adhesion of L. mesenteroides to the human gut epithelial cell line. Butyrate from L. mesenteroides in the presence of linoleic acid were detectable and mediated free fatty acid receptor 2 (Ffar2) to reduce the lipid contents in differentiating 3T3-L1 adipocytes. Oral administration of L. mesenteroides plus linoleic acid remarkably reduced high-fat-diet (HFD)-induced formation of 4-hydroxy-2-nonenal (4-HNE), a reactive oxygen species (ROS) biomarker, and decreased abdominal fat mass in mice. The reduction of 4-HNE and abdominal fat mass was reversed when cyclophilin A inhibitor-pretreated bacteria were administered to mice. Our studies present a novel mechanism of reducing abdominal fat mass by electrogenic L. mesenteroides which may yield electrons to enhance colonization and sustain high amounts of butyrate to limit ROS during adipocyte differentiation.

Production of electricity and reduction of high-fat diet-induced IL-6 by glucose fermentation of Leuconostoc mesenteroides.

Electrogenic bacteria can mediate electron transfer to conserve energy and promote growth. To examine bacterial electrogenicity, an L. mesenteroides EH-1 strain was cultured in rich media in the presence and absence of 2% glucose. After 12 h incubation, glucose triggered fermentation of L. mesenteroides EH-1 to produce >10 mmol/l acetate and elicit electricity measured by voltage changes. The electricity production was mediated by glucose fermentation since pre-treatment of L. mesenteroides EH-1 with furfural, a fermentation inhibitor, completely diminished the voltage increases. The deficiency of furfural pre-treated L. mesenteroides EH-1 in electricity production can be restored by the external addition of acetate into the bacterial culture, suggesting the function of acetate as an electron donor. Oral administration of HFD-fed mice with L. mesenteroides EH-1 in the presence or absence of glucose significantly attenuated the high level of pro-inflammatory IL-6 cytokine in blood. Bacterial electricity can be elicited by fermentation. Supplementation of fermenting and electrogenic L. mesenteroides EH-1 may provide a novel approach for the reduction of pro-inflammatory IL-6 cytokine that increased in chronic inflammation, autoimmune diseases, cancers, and infections.

Mouse Abdominal Fat Depots Reduced by Butyric Acid-Producing Leuconostoc mesenteroides.

The activation of peroxisome proliferator-activated rece ptor gamma (PPAR-γ) is known to induce the differentiation of adipocytes. This study aimed to investigate the probiotic effect of Leuconostoc mesenteroides (L. mesenteroides) on high-fat diet (HFD)-induced PPAR-γ activation and abdominal fat depots. Incubation of differentiated 3T3-L1 adipocytes with media of L. mesenteroides EH-1, a butyric acid-producing strain, significantly reduced the amounts of lipid droplets. The oral administration of L. mesenteroides EH-1 produced large amounts (>1 mM) of butyric acid in cecum and attenuated the HFD-induced upregulation of PPAR-γ and accumulation of abdominal fats in mice. The combination of 2% glucose with L. mesenteroides EH-1 increased the production of butyric acid and potentiated the probiotic activity of L. mesenteroides EH-1 against the formation of lipid droplets in 3T3-L1 adipocytes as well as abdominal fats in HFD-fed mice. The inhibition of free fatty acid receptor 2 (Ffar2) by its antagonist, GLPG-0974, markedly diminished the probiotic effects of L. mesenteroides EH-1 plus glucose on the suppression of HFD-induced PPAR-γ and abdominal fats. Besides demonstrating the probiotic value of L. mesenteroides EH-1, our results highlight the possible therapy targeting the butyric acid-activated Ffar2 pathway to reduce abdominal fats.