Front Nutr. 2026 Sep 22;13:1931405. doi: 10.3389/fnut.2026.1931405. eCollection 2026.
ABSTRACT
Rapid global population ageing is accelerating the burden of cardiometabolic disease, and inflammageing-the chronic, low-grade, sterile inflammation that accompanies advancing age-has emerged as a shared pathological substrate linking cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus in older adults. Increasing evidence identifies the gut microbiota as an upstream driver of this process, forming a modifiable feedback loop with the intestinal barrier, the immune system, and cardiometabolic homeostasis. With advancing age, beneficial taxa such as Bifidobacterium and Faecalibacterium prausnitzii decline in abundance, whereas pro-inflammatory taxa expand; this dysbiosis compromises tight-junction integrity, producing the "leaky gut" phenotype and permitting translocation of lipopolysaccharide and other pathogen-associated molecular patterns into the portal circulation. The resulting metabolic endotoxaemia activates TLR4/NF-κB signalling and sustains systemic elevations of IL-6, TNF-α, and IL-1β, which converge on insulin resistance, endothelial dysfunction, oxidative stress, and vascular injury. Microbiota-derived metabolites further shape this trajectory: trimethylamine-N-oxide (TMAO) has been implicated in the acceleration of atherosclerosis, foam-cell formation, and platelet reactivity-largely on the basis of rodent studies and observational human data-whereas short-chain fatty acids reinforce barrier function and induce regulatory T cells. This review systematically synthesises current mechanistic and clinical evidence on the gut microbiota-inflammageing axis and its contribution to cardiometabolic deterioration during ageing, and critically appraises dietary intervention strategies as the most direct and actionable entry point into this feedback loop. The Mediterranean, Green-Mediterranean, and plant-based dietary patterns, together with intermittent fasting, have been shown to remodel the gut microbiota, reduce systemic inflammatory tone, and improve cardiometabolic risk profiles. Key dietary components-fibre-derived short-chain fatty acids, polyphenols and their microbial metabolites, omega-3 polyunsaturated fatty acids together with specialised pro-resolving mediators, and age-appropriate protein intake-act through distinct but converging molecular mechanisms to preserve barrier integrity, restore immunometabolic balance, and support healthy vascular ageing. Emerging translational approaches, including precision nutrition guided by individual microbiome profiles, next-generation probiotics, prebiotics and postbiotics, and small-molecule inhibitors targeting TMAO biosynthesis, are also examined, alongside their current translational limitations-including the absence of standardised microbiome analytical pipelines, strain-specific heterogeneity of probiotic effects, and the lack of formal recommendations in current cardiovascular and diabetes guidelines. Safety considerations relevant to frail older adults-such as hypoglycaemia risk during intermittent fasting, bleeding risk with high-dose omega-3 supplementation, and rare bacteraemia associated with probiotic use in immunocompromised individuals-are also highlighted. Research gaps such as scarce long-term follow-up, under-representation of non-Western populations, and heterogeneity across ageing stages are discussed. By integrating mechanistic insight with translational evidence, this review provides a theoretical foundation for the development of individualised nutritional strategies aimed at extending cardiometabolic healthspan in older adults.
PMID:42840755 | PMC:PMC13641114 | DOI:10.3389/fnut.2026.1931405