Luting Hu

Obesity is associated with impaired intestinal barrier function and dysbiosis of the gut microbiota. Spermidine, a polyamine that acts as an autophagy inducer, has important benefits in patients with aging-associated diseases and metabolic dysfunction. However, the mechanism of spermidine on obesity remains unclear. Here, we show that spermidine intake is negatively correlated with obesity in both humans and mice. Spermidine supplementation causes a significant loss of weight and improves insulin resistance in diet-induced obese (DIO) mice. These effects are associated with the alleviation of metabolic endotoxemia and enhancement of intestinal barrier function, which might be mediated through autophagy pathway and TLR4-mediated microbial signaling transduction. Moreover, spermidine causes the significant alteration of microbiota composition and function. Microbiota depletion compromises function, while transplantation of spermidine-altered microbiota confers protection against obesity. These changes might partly be driven by an SCFA-producing bacterium, Lachnospiraceae NK4A136 group, which was decreased in obese subjects and subsequently increased by spermidine. Notably, the change of Lachnospiraceae NK4A136 group is significantly correlated with enhanced gut barrier function induced by spermidine. Our results indicate that spermidine supplementation may serve as a viable therapy for obesity.

Inflammatory bowel disease (IBD) is associated with acute and chronic inflammation of the gastrointestinal tract and has emerged to be a global disease. Spermidine, a natural polyamine, plays a critical role in maintaining cellular homeostasis. Herein, we investigated the impact and mechanism of spermidine on both dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced colitis in mice. We found that spermidine exerted protective effects against acute colitis, evidenced by reduced disease activity index (DAI) and colonic inflammation, increased colonic length, and upregulated tight junction proteins in these two colitis models. Importantly, spermidine exerted significant therapeutic and preventive effects against DSS-induced colitis. Pre- and post-treatment with spermidine reduced the expression of proinflammatory cytokines, phosphorylation of (nuclear factor-κB) NF-κB and (mitogen-activated protein kinase) MAPK, and the activation of F4/80 macrophages and T cells in the colon. Furthermore, spermidine upregulated M2 macrophage markers, whereas it downregulated M1 markers in the inflamed colons. In parallel, spermidine reduced M1 pro-inflammatory markers and enhanced M2 anti-inflammatory genes in RAW264.7 cells. These results revealed that spermidine-ameliorated colitis might be through the regulation of M1/M2 macrophage polarization. In addition, spermidine treatment also alleviated LPS/TNF-α-induced inflammation in Caco-2 cells. Taken together, spermidine prevented and reversed colonic inflammation in colitis mice and might be a promising candidate for IBD intervention.

SCOPE: The impacts of longevity-promoting probiotic Bifidobacterium animalis subsp. lactis LKM512 (LKM512) on metabolic disease remain unclear. Here, the authors aim to explore the potential of LKM512 on the host physiological function and gut microbiota in high-fat diet-induced obese mice. METHODS AND RESULTS: LKM512 are orally administrated for 12 weeks, and the effects of LKM 512 on systemic inflammation and insulin resistance, as well as gut microbiota, are investigated in high-fat (HF) diet-induced obese mice. LKM512 supplementation ameliorates hepatic lipid accumulation, attenuates hepatic and adipose tissue inflammation, and improves intestinal barrier function. These results are associated with improved insulin sensitivity and metabolic endotoxemia. Furthermore, the colonization of LKM512 induces an increase in polyamine metabolism and production, together with significant alternations in the composition and function of gut microbiota in obese mice, which are correlated with these improved metabolic phenotypes in the host. CONCLUSION: The probiotic strain LKM512 may become a promising strategy to improve obesity and related metabolic disorders.