Natural products as modulators of age-associated gut microbiota dysbiosis: a systematic review of animal models

Abstract

Ageing is increasingly recognised as a microbiota-driven process, with dysbiosis contributing to oxidative stress, chronic inflammation, and cognitive and functional decline. Natural products, long valued in traditional medicine, are emerging as targeted modulators of the gut ecosystem. This systematic review synthesised current evidence on natural product interventions in ageing animal models. Searches of four databases (2000–2024) yielded 762 records, of which 17 studies met eligibility criteria, encompassing naturally aged rodents, D-galactose-induced, genetically accelerated (SAMP8, ob/ob), and diet-induced models. Interventions spanned plant-derived compounds, probiotics, prebiotics, marine microalgae, and animal-derived products. Across models, natural products frequently normalized microbial communities, lowering the Firmicutes/Bacteroidetes ratio, suppressing pro-inflammatory taxa (Helicobacter, Desulfovibrio), and enriching beneficial genera (Lactobacillus, Bifidobacterium, Akkermansia). These shifts are linked to improved systemic outcomes, including enhanced antioxidant defences (SOD, GSH-Px, CAT), reduced levels of inflammatory mediators (IL-6, TNF-α, COX-2), and gains in memory, learning, and motor performance. Taken together, these findings demonstrate that natural products exert multi-targeted benefits in ageing by restoring microbial balance and attenuating hallmarks of decline. Yet, wide heterogeneity in animal models, intervention types, and outcome measures limits comparability. Standardised, long-term, and multi-omics approaches are urgently needed to establish mechanistic pathways and accelerate translation into human ageing interventions. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420250602174.