Deciphering the mitochondria–gut microbiota axis in irritable bowel syndrome: pathogenic insights and therapeutic frontiers

Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder involving multiple pathogenic mechanisms. Gut microbiota dysbiosis and mitochondrial dysfunction are key drivers of IBS, as they weaken the intestinal barrier, promote inflammation, and alter metabolism. However, the underlying mechanisms of crosstalk between these factors remain largely understudied, which hinders the clinical translation of targeted therapeutic strategies. Drawing on recent literature, this review clarifies the intricate interplay between mitochondrial health and gut microbiota balance in IBS. We summarize the core pathophysiological mechanisms of IBS including neuroendocrine, immune-inflammatory, and gastrointestinal motility-related pathways. We further elaborate on the individual roles of mitochondrial dysfunction and gut microbiota dysbiosis in IBS pathogenesis, discussing the bidirectional crosstalk between mitochondria and the gut microbiota, and the regulatory role of diet in this axis. Current therapeutic approaches targeting IBS, such as Western medications; probiotics; fecal microbiota transplantation; low-fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diet; traditional Chinese medicine; and mitochondria-targeted interventions, are also reviewed. Building on this, the review summarizes the advantages and limitations of existing research on the mechanisms and therapies for IBS and identifies the challenges and directions for future basic and clinical research. The interplay between mitochondrial dysfunction and gut microbiota dysbiosis is a critical research focus for understanding IBS pathophysiology. Elucidating the underlying mechanisms of their crosstalk provides a foundation for future research and facilitates the development of innovative therapeutic strategies targeting mitochondrial health and gut microbiota balance. This multifaceted approach holds promise for improving IBS management and enhancing the quality of life of affected patients.