The Gut Microbiota and Oxidative Stress as Converging Mechanisms in Environmental Chemical-Mediated Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a complex autoimmune disease (AD) characterized by chronic inflammation and multi-organ damage, driven by a combination of genetic, hormonal and environmental factors. Ample evidence links specific environmental agents, such as solvents, PFAS, microplastics, bisphenol A, mercury, pesticides, smoking and silica, to the development of SLE. Despite growing evidence highlighting the pivotal role of these environmental agents in initiating, modulating or exacerbating autoimmune responses, substantial gaps remain in our understanding of their precise role and mechanisms driving disease pathogenesis. Oxidative stress (OS) plays an important role in the pathogenesis of a variety of ADs, including SLE, and many environmental factors actively participate in this process. Furthermore, with the recent surge in microbiome research, numerous studies have provided insight into how changes in the gut microbiota contribute to the onset and progression of the disease. Importantly, understanding the interplay among OS, gut dysbiosis, and immune dysregulation will not only deepen our insight into environmental pathophysiology but also open new avenues for microbiota-targeted prevention and therapy in SLE. This review aims to provide an updated overview of the existing literature concerning the role of gut microbiome-OS-host interactions in the pathogenesis of SLE, while also exploring potential novel therapies.