Combined Probiotics and Phenolics in Western Diet-fed Rats Enhance Parasympathetic Tone in the Gut–Brain Axis by Attenuating Inflammasome Signaling, and Reshaping Gut Microbiome

Western dietary patterns are major drivers of cardiometabolic dysfunction, partly mediated by gut microbiome dysbiosis and sustained inflammation along the gut-brain axis. In this study, we investigated whether a synbiotic formulation combining Limosilactobacillus (L.) fermentum strains with polyphenols, quercetin, and resveratrol could mitigate cardiovascular and neuroinflammatory alterations induced by a Western diet. Male Wistar rats were assigned to three groups receiving a standard diet, a Western diet, or a Western diet supplemented with the synbiotic. Arterial pressure and cardiac autonomic function were assessed, alongside gut microbiome diversity and composition, and gene expression analyses of intestinal permeability and inflammatory markers in colonic tissue and in the brainstem. Synbiotic supplementation prevented the Western diet-induced cardiac autonomic imbalance. These functional benefits were accompanied by marked modulation of the gut microbiome, characterized by increased abundance of beneficial bacterial taxa (Gemmiger formicilis, Lactobacillus acidophilus, Flavonifractor plautii, Blautia glucerasea, Blautia stercoris, Roseburia faecis, Marvinbryantia formatexigens, and Romboutsia timonensis) and significant shifts in microbial community structure. In parallel, synbiotic supplementation attenuated pro-inflammatory gene expression in both peripheral and central tissues associated with the gut-brain axis (Nlrp3, Casp1, Il-1β). These findings demonstrate that synbiotic supplementation exerts integrated anti-inflammatory and neuroautonomic protective effects through the gut-brain axis. Our results support the therapeutic potential of combined probiotic-phenolic strategies to counteract cardiometabolic dysfunction induced by Western diets.