Spermidine improves gut barrier integrity and gut microbiota function in diet-induced obese mice

Abstract

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 SCFAproducing 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.

Intestinal microbiota influences clinical outcome and side effects of early breast cancer treatment

“…Polyamines constitute major products of the colonic microbiota, as shown after oral administration of the immunogenic commensal A. muciniphila [ 43 ]. Polyamines can improve the intestinal barrier function [ 44 ] and cancer immune-surveillance [ 45 ].…”

Oral administration of Akkermansia muciniphila elevates systemic antiaging and anticancer metabolites

“…The nutritional uptake of polyamines has been correlated with reduced mortality from cancer and cardiovascular disease in two independent population studies [ 36 , 37 ]. Moreover, in mice, spermidine improve the gut barrier function [ 38 ] and has marked antiobesity, antidiabetic and cancer immunosurveillance-improving effects [ 39 – 41 ]. These effects of polyamines are due to the induction of autophagy in host cells [ 40 , 42 , 43 ].…”

Symbiotic polyamine metabolism regulates epithelial proliferation and macrophage differentiation in the colon

“…We previously reported that the abundance of luminal polyamines is positively correlated with longevity in mice 5 . Likewise, exogenous spermidine administration extends the lifespan in model organisms and improves cardiac dysfunction as well as metabolic syndrome in mice by inducing autophagy [6][7][8] . Furthermore, the enhancement of luminal putrescine production by administration of probiotics and arginine improved reactive hyperaemia index representing endothelial function in randomised controlled clinical trial 9 .…”