Liujie Zheng

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.

SCOPE: Age-related degeneration is associated with imbalances of gut microbiota and its related immune system, thus gut microbiota dysbiosis is considered to be a key target to improve senescence. The potential roles of probiotics on physiological function and cognitive ability in aged mice are investigated in this study. METHODS AND RESULTS: Lactobacillus casei LC122 or Bifidobacterium longum BL986, are orally administrated for 12 weeks, and the anti-aging effects, as well as the composition and function of gut microbiota, are investigated in aged mice. Probiotics supplementation ameliorates hepatic lipid accumulation, enhances muscle strength and function, attenuates oxidative stress and inflammation in peripheral tissues, and improves gut barrier function. These results are associated with improved learning and memory ability as assessed by behavioral tests and upregulation of neurodegenerative and neurotrophic factors expressions in hippocampus. Moreover, the diversity and composition of gut microbiota are altered in aged mice, and both probiotics treatment display distinguished features of gut microbiota. Comparisons of two probiotic strains reveal significant differences in the taxa at family and genus level, leading to the functional profile change of the microbial community. CONCLUSION: L. casei LC122 and B. longum BL986 might be used as novel and promising anti-aging agents in human.

SCOPE: Irregular eating habits, such as late-night eating, will cause increased risk of obesity and other metabolic diseases. The aim of this study is to elucidate the impacts of late-night eating on physiological function and gut microbiota. METHODS AND RESULTS: Male Wistar rats under 16 h/8 h-light/dark cycle are divided into four groups with specific dietary habits, which mimicked breakfast, lunch, dinner, and late-night eating. Late-night eating, including skipping dinner for a night eating (BLN) and skipping breakfast and having a night eating (LDN), causes an increase of body weight, which is associated with decreased physical activity. Additionally, late-night eating results in hepatic lipid accumulation and systemic inflammation in peripheral tissues, compared to those of free feeding (FF) or breakfast, lunch, and dinner (BLD) groups. The phases of key clock genes are similar in FF, BLD, and BLN groups, while LDN feeding causes an overall 4 h phase delay in peripheral tissues. Moreover, late-night eating, especially LDN feeding, results in a significant alternation in the compositions and functions of gut microbiota, which further contributes to the development of metabolic disorder. CONCLUSION: Late-night eating causes physiological dysregulation and misalignment of circadian rhythm, together with microbial dysbiosis.