Beyond the gut—dietary fiber mediated interorgan crosstalk and systemic health: Mechanistic insights and human evidence

Dietary fibers (DFs) are increasingly recognized as key modulators of systemic physiology, exerting effects beyond the gastrointestinal tract through coordinated interorgan communication. Advances in nutrition and microbiome research indicate that physicochemical properties of DFs, including structure, viscosity, fermentability, and molecular weight, shape their metabolic and immunological functions. By serving as substrates for microbial fermentation, DFs promote the production of short‑chain fatty acids and other bioactive metabolites that influence epithelial integrity, immune regulation, bile‑acid signaling, and host metabolic pathways across multiple gut–organ axes. Human studies consistently demonstrate that higher fiber intake is associated with reduced cardiovascular risk, improved hepatic lipid metabolism in non‑alcoholic fatty liver disease, lower gut‑derived uremic toxins in chronic kidney disease, enhanced pulmonary outcomes in inflammatory airway diseases, and potential benefits for mood, cognition, and sleep via neuroimmune pathways. Despite these well-established effects, global intake remains below recommended levels (25–38 g/day), contributing to a measurable burden of noncommunicable diseases, including an estimated ∼453,000 deaths attributable to low fiber intake worldwide. This review provides a focused synthesis of DF-mediated interorgan crosstalk by integrating mechanistic insights with human evidence across major gut–organ axes, with particular emphasis on the role of fiber characteristics in shaping clinical outcomes. Collectively, the evidence positions DFs as a low‑risk, scalable, and mechanism‑guided intervention for improving systemic health. Addressing the global “fiber gap” represents a promising strategy for reducing chronic disease risk through precision nutrition approaches. However, the current evidence remains heterogeneous, with several extraintestinal outcomes supported mainly by observational studies and a limited number of long-term randomized trials.