The gut microbiota, shaped by factors such as diet, lifestyle, and genetics, plays a pivotal role in regulating host metabolism, immune function, and overall health. The diversity and balance of the gut microbiota are closely linked to the onset and progression of various chronic diseases. A growing body of evidence has demonstrated that alterations in the composition, function, and metabolites of the gut microbiota are significantly associated with cardiovascular diseases, including hypertension, atherosclerosis, and heart failure; metabolic disorders such as obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease; and gastrointestinal conditions like inflammatory bowel disease and colorectal cancer. Despite substantial advances in microbiome research, challenges remain in fully elucidating the causal relationships between the gut microbiota and disease, as well as in translating these insights into clinical applications. This review aims to investigate the regulatory pathways via which the gut microbiota affects cardiovascular health, metabolic function, and gastrointestinal disease. Additionally, it highlights emerging strategies for the prevention and treatment of these chronic conditions, focusing on microbiota-targeted therapies and personalized dietary interventions as promising approaches for improving health outcomes.

The pregnane X receptor (PXR), a ligand-activated nuclear receptor, plays a central role in regulating the metabolism of both endogenous substances and xenobiotics. In recent years, increasing evidence has highlighted its involvement in chronic diseases, particularly metabolic disorders and cancer. PXR modulates drug-metabolizing enzymes, transporters, inflammatory factors, lipid metabolism, and immune-related pathways, contributing to the maintenance of hepatic–intestinal barrier homeostasis, energy metabolism, and inflammatory responses. Specifically, in type 2 diabetes mellitus (T2DM), PXR influences disease progression by regulating glucose metabolism and insulin sensitivity. In obesity, it affects adipogenesis and inflammatory processes. In atherosclerosis (AS), PXR exerts protective effects through cholesterol metabolism and anti-inflammatory actions. In metabolic dysfunction-associated steatotic liver disease (MASLD), it is closely associated with lipid synthesis, oxidative stress, and gut microbiota balance. Moreover, PXR plays dual roles in various cancers, including hepatocellular carcinoma, colorectal cancer, and breast cancer. Currently, PXR-targeted strategies, such as small molecule agonists and antagonists, represent promising therapeutic avenues for treating metabolic diseases and cancer. This review comprehensively summarizes the structural features, signaling pathways, and gene regulatory functions of PXR, as well as its role in metabolic diseases and cancer, providing insights into its therapeutic potential and future drug development challenges.

Polysaccharides derived from edible fungi can alleviate ulcerative colitis (UC) by enriching beneficial probiotics. However, the mechanisms underlying their interaction with probiotics remain unclear. Here, The current study investigated how Poria cocos polysaccharide (PCP) enriches L. gasseri and the effects of L. gasseri on dextran sulfate sodium (DSS)-induced UC. Genomic analyses predicted multiple polysaccharide utilization loci in L. gasseri, and growth kinetics together with gene expression assays confirmed that PCP promoted L. gasseri growth and upregulated glycoside hydrolases (GH1 and GH3). In UC induced mice, L. gasseri alleviated weight loss, colon shortening, and Disease activity index score, increased goblet cells, and decreased pro-inflammatory cytokines. In addition, targeted metabolomics revealed that L. gasseri intervention was associated with the restoration of indole-3-lactic acid (ILA) and indole-3-propionic acid (IPA) levels in the tryptophan-indole metabolic pathway. RT-qPCR, Western blot, and immunofluorescence analyses showed that L. gasseri intervention induced the upregulation of AHR expression and the downstream genes CYP1A1 and IL-22. Treatment with the AHR antagonist CH223191 further confirmed that the anti-inflammatory and barrier-protective effects were dependent on the AHR pathway. Notably, It was further verified through ABX depletion experiments that PCP exerts its indirect therapeutic effect via L. gasseri. Consequently, this study provided new insights into the interaction between PCP and probiotics the mechanism underlying the protective role of L. gasseri in the intestinal barrier, and proposes promising preliminary combination strategy for the treatment and prevention of UC.