Pyroptosis the Emerging Link Between Gut Microbiota and Multiple Sclerosis

Hua Fan,* Ruile Shen,* Junqiang Yan,* Yongjie Bai, Qizhi Fu, Xiaofei Shi, Ganqin Du, Dongmei Wang The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, 471003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ganqin Du; Dongmei Wang, Email [email protected]; [email protected]: This review elucidates the pivotal role of pyroptosis, triggered by gut microbiota, in the development of multiple sclerosis (MS), emphasizing its significance within the gut-brain axis. Our comprehensive analysis of recent literature reveals how dysbiosis in the gut microbiota of MS patients—characterized by reduced microbial diversity and shifts in bacterial populations—profoundly impacts immune regulation and the integrity of the central nervous system (CNS). Pyroptosis, an inflammatory form of programmed cell death, significantly exacerbates MS by promoting the release of inflammatory cytokines and causing substantial damage to CNS tissues. The gut microbiota facilitates this detrimental process through metabolites such as short-chain fatty acids and neuroactive compounds, or self-structural products like lipopolysaccharides (LPS), which modulate immune responses and influence neuronal survival. This review highlights the potential of modulating gut microbiota to regulate pyroptosis, thereby suggesting that targeting this pathway could be a promising therapeutic strategy to mitigate inflammatory responses and preserve neuronal integrity in patients with MS.Keywords: multiple sclerosis, gut microbiota, pyroptosis, gut-brain axis, neuroinflammation, therapeutic targets