Gut microbiota-fatty acid oxidation interplay in aging: Mechanisms, controversies, and translational perspectives

Table 1 Microbiota-derived mediators potentially linking gut microbiota remodeling to fatty acid oxidation during aging

Mediator	Microbial source or pathway	Major host targets	Proposed link to fatty acid oxidation	Relevance to aging	Ref.
Short-chain fatty acids	Fermentation of dietary fiber by commensal bacteria	AMP-activated protein kinase, hepatic substrate utilization, mitochondrial metabolism	May influence substrate preference, improve metabolic flexibility, and modulate oxidative metabolism	Aging is often accompanied by reduced short-chain fatty acid production and loss of short-chain fatty acid-producing taxa	[13,30,31]
Secondary bile acids	Microbial transformation of primary bile acids	Farnesoid X receptor, Takeda G protein-coupled receptor 5, mitochondrial signaling	May reshape lipid handling, energy expenditure, and host oxidative metabolism	Centenarian-associated microbiota shows distinct bile acid-related functional signatures	[11,14,32,33]
Lipid-derived microbial signals	Microbiota-associated lipid processing and metabolite generation	Mitochondrial function, inflammatory tone, insulin sensitivity	May indirectly alter fatty acid oxidation through changes in redox balance and substrate availability	Likely contributes to tissue-specific metabolic remodeling during aging	[28,29,44,46]
Inflammatory mediators linked to dysbiosis	Barrier dysfunction, endotoxin exposure, altered microbial ecology	Immune-metabolic signaling, mitochondrial stress pathways	May shift host metabolism away from coordinated oxidative balance and promote maladaptive fatty acid oxidation responses	Chronic low-grade inflammation is a common feature of aging and microbial dysbiosis	[8,18,37,47]
Diet-microbiota interaction	Dietary fiber, fat quality, long-term dietary patterns	Microbial metabolite production, host substrate availability	May modify fatty acid oxidation indirectly by altering metabolite pools and nutrient flow	Especially relevant for translational strategies in older adults	[48-50,57]
Microbiota transfer or ecological manipulation	Fecal microbiota transplantation, microbiota-targeted interventions	Whole-body metabolic phenotype, tissue energetics	Useful for testing whether microbial states causally modify fatty acid oxidation-related phenotypes	Provides experimental leverage, but direct tissue-specific fatty acid oxidation effects remain insufficiently defined	[22,39,41,60]