Microbiota-driven mechanisms in multisystem diseases: integrative evidence across cardiovascular, metabolic, neurological and autoimmune disorders

Abstract

The human microbiota represents one of the body's most influential biological systems, engaging in constant metabolic, immunological, and neuroendocrine communication with the host. Disruption of this intricate ecosystem, or dysbiosis, has emerged as a fundamental determinant in the onset and progression of numerous chronic diseases. This review consolidates contemporary evidence on how alterations in microbial composition, metabolite production, and barrier integrity contribute to pathophysiological changes across multiple organ systems. Gut-derived metabolites-including short-chain fatty acids, bile acid derivatives, trimethylamine-N-oxide, and lipopolysaccharide-serve as key mediators linking microbial imbalance to systemic inflammation, metabolic dysfunction, autoimmunity, and neurodegeneration. We outline the mechanistic pathways through which dysbiosis promotes hypertension, atherosclerosis, obesity, type 2 diabetes, Parkinson's disease, Alzheimer's disease, rheumatoid arthritis, inflammatory bowel disease, asthma, chronic obstructive pulmonary disease, urinary tract infections, and chronic kidney disease. Particular emphasis is placed on the gut-brain, gut-lung, and gut-kidney axes, which facilitate bidirectional immune and metabolic signalling between the intestine and distant tissues. Additionally, the review highlights emerging therapeutic interventions aimed at restoring microbial homeostasis, including targeted dietary strategies, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and microbiome-directed pharmacological approaches. Collectively, the evidence positions the microbiota as a central regulator of human health and disease, offering a compelling platform for next-generation diagnostic and therapeutic innovation. Advancing mechanistic understanding of host-microbe interactions will be essential to developing personalized microbiome-based strategies capable of preventing, mitigating, or reversing disease across diverse clinical contexts.

Keywords: Gut microbiota; Gut-brain axis; Metabolic disorders; Microbiome dysbiosis; Microbiome-targeted therapies.