These findings support a gut microbiota-butyrate-PPARγ/p21 axis through which soybean polysaccharide protects against aging-related endothelial dysfunction, providing a nutritional basis for targeting the gut-vascular axis in cardiovascular aging.
Twelve weeks of soybean polysaccharide (SP) supplementation restored endothelium-dependent relaxation in 20-month-old naturally aged mice.
SP reduced markers of vascular oxidative stress and endothelial activation in the aorta of aged mice.
SP attenuated colon senescence, improved gut barrier integrity, and reduced systemic inflammation in aged mice.
SP enriched butyrate-producing gut bacteria and increased gut and serum butyrate.
Direct butyrate supplementation reproduced the vascular and colonic benefits seen with SP.
Butyrate activated PPARγ signaling and downregulated senescence and adhesion molecules, while PPARα and PPARδ were unchanged.
The authors propose a gut microbiota–butyrate–PPARγ/p21 axis through which SP protects against aging-related endothelial dysfunction.
This study in naturally aged mice (20 months old) tested whether soybean polysaccharide, a dietary fiber-like compound from soybeans, could protect blood vessels from aging. After 12 weeks of supplementation, the mice's blood vessels relaxed better, and there were fewer signs of oxidative stress and inflammatory adhesion molecules in the aorta. The gut also looked healthier: signs of colon aging were lower, the gut barrier was improved, and blood levels of inflammatory and gut-derived compounds (LPS, IL-1β, TNF-α, and TMA/TMAO) were reduced. The researchers found that soybean polysaccharide increased gut bacteria that produce butyrate, a short-chain fatty acid, and raised butyrate levels in the gut and blood. Giving butyrate directly produced similar benefits for blood vessels and colon. Butyrate appeared to work by activating a cellular pathway called PPARγ and lowering aging-related proteins such as p21 and p16, as well as adhesion molecules ICAM-1 and VCAM-1. Two related pathways, PPARα and PPARδ, were not changed. This research suggests that diet-based approaches that support gut bacteria may help protect blood vessels during aging via a gut-to-blood-vessel connection. These findings come from mice, so whether the same effects occur in people remains to be tested.
Zhang Q, Zhou Z, Yeung H, Cheung Y, Wong Y, He C, et al.. (2026). PPARγ/P21 Signaling Mediates Butyrate-Driven Protection against Aging-Related Endothelial Dysfunction: A Novel Effect of Soybean Polysaccharide via the Gut-Vascular Axis.. Journal of agricultural and food chemistry. https://doi.org/10.1021/acs.jafc.6c10019