Gut microbiota: origin or panacea for all ills? Gut microbiota and systemic diseases

Chronic non-communicable diseases (CNCDs) extend beyond the metabolic domain, affecting neurological, cardiovascular, rheumatologic, respiratory, gastrointestinal, and renal systems. These conditions share underlying mechanisms involving low-grade inflammation, immune dysregulation, and metabolic imbalance, often influenced by gut microbiota alterations. The microbiota mediates systemic effects via microbial metabolites, immune modulation, and barrier integrity. Recent research has highlighted that these microbiota-mediated interactions are not unidirectional but involve complex bidirectional signaling between the gut and distal organs. Microbial metabolites such as short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), and tryptophan-derived indoles are messengers that influence neuroinflammation, endothelial function, immune responses, and even behavior. The gut microbiota is now viewed as an endocrine-like organ that can modulate systemic physiology. Understanding these pathways has opened new avenues for treating systemic diseases by modulating the gut ecosystem, offering novel perspectives for therapeutic intervention in conditions that were traditionally managed without considering microbiota. • CNCDs affect multiple organ systems and are characterized by low-grade inflammation and immune dysregulation. • Gut microbiota alterations play a crucial role in mediating systemic effects through microbial metabolites and immune modulation. • Gut microbiota influences health via complex signaling pathways, that connect gut and brain (gut-brain axis), gut and lungs (gut-lung axis), and gut and kidneys (gut-kidney axis), impacting systemic inflammation and functionality. • Dysbiosis is linked to various CNCDs, such as cardiovascular, gastrointestinal, neurodegenerative, respiratory, rheumatologic, renal, and neuropsychiatric ones. In fact, specific microbial taxa are associated with various disease severity and progression. • Microbial metabolites such as short-chain fatty acids (SCFAs) are vital for maintaining systemic health, reducing inflammation. • Biomodulators and FMT show promise in restoring gut microbiota balance and improving outcomes in certain systemic diseases. Ongoing studies are exploring their potential in treating CNCDs. • Advances in microbiome research are paving the way for precision medicine approaches, including personalized biomodulators and targeted dietary interventions. • Longitudinal studies and clinical trials are needed to precisely establish causal relationships and therapeutic efficacy of microbiota modulation.