The Gut Microbiota-Produced Indole-3-Propionic Acid Confers the Antihyperlipidemic Effect of Mulberry-Derived 1-Deoxynojirimycin

Abstract

Hyperlipidemia has been intensively focused on by researchers around the world owing to its major contribution to cardiovascular diseases. Various evidence reveals that women are more susceptible than male counterparts to dyslipidemia, making sex-dependent therapeutic strategies and drugs urgently needed. In the present work, we demonstrate that DNJ, the main active component of mulberry leaves, exerts an obvious female-preferential antihyperlipidemic effect through specifically enriching Akkermansia and Clostridium XIVa and elevating an active microbial metabolite, indole-3-propionic acid (IPA), in female mice. Moreover, we have corroborated the potent lipid-lowering efficacy of IPA both in vitro and in vivo. These findings not only indicate a potential mechanism by which gut microbes and their metabolites confer the beneficial role of DNJ in ameliorating hyperlipidemia but also provide an in-depth theoretical basis for therapeutic exploitation of DNJ as a female-specific intervention against hyperlipidemia.

Feeding of cuticles from Tenebrio molitor larvae modulates the gut microbiota and attenuates hepatic steatosis in obese Zucker rats

“…76 In addition, cell culture studies reported that IPA decreases paracellular permeability by increasing expression of tight junction proteins and strengthening the mucus barrier in intestinal epithelial cells 77 and lowers lipid accumulation in liver cells. 78 Thus, these findings suggest that feeding of dietary insects’ cuticles has improved the gut barrier function, likely as a consequence of the modulation of the gut microbiota composition. In agreement with this, a recent study clearly demonstrated that chitin oligosaccharides – one of the main components of insects’ cuticles – strongly increased the expression of tight junction-related genes, such as tight junction protein ( Tjp ) 1 and Tjp2 and occludin in the distal small intestine of mice.…”

Indole-3-Propionic Acid as a Potential Therapeutic Agent for Sepsis-Induced Gut Microbiota Disturbance

“…The beneficial effects of IPA on multiple diseases such as steatohepatitis, hyperlipidemia, and diabetes have been demonstrated ( 18 , 30 , 31 ). IPA also modulates astrocyte activation and neuroinflammation and inhibits neuronal death induced by endoplasmic reticulum stress ( 32 ).…”

Dose-Dependent Beneficial Effects of Tryptophan and Its Derived Metabolites on Akkermansia In Vitro: A Preliminary Prospective Study

“…IPA could maintain the integrity of the intestinal barrier via pregnant X receptor and toll-like receptor 4 [ 38 ]. Meanwhile, Li et al observed that 1-deoxynojirimycin treatment significantly increased the level of IPA in the feces of mice, and simultaneously enriched Akkermansia [ 39 ]. These results revealed that A. muciniphila might be able to utilize the tryptophan metabolites, which are produced by other commensal intestinal flora.…”