Environmental Exposures and Autoimmune Diseases: Contribution of Gut Microbiome

Abstract

Environmental agents have been gaining more attention in recent years for their role in the pathogenesis of autoimmune diseases (ADs). Increasing evidence has linked environmental exposures, including trichloroethene (TCE), silica, mercury, pristane, pesticides, and smoking to higher risk for ADs. However, potential mechanisms by which these environmental agents contribute to the disease pathogenesis remains largely unknown. Dysbiosis of the gut microbiome is another important environmental factor that has been linked to the onset of different ADs. Altered microbiota composition is associated with impaired intestinal barrier function and dysregulation of mucosal immune system, but it is unclear if gut dysbiosis is a causal factor or an outcome of ADs. In this review article, we first describe the recent epidemiological and mechanistic evidences linking environmental/occupational exposures with various ADs (especially SLE). Secondly, we discuss how changes in the gut microbiome composition (dysbiosis) could contribute to the disease pathogenesis, especially in response to exposure to environmental chemicals.

Keywords: autoimmune diseases; dysbiosis; environmental agents; microbiome; oxidative stress.

Figure 1

Schematic presentation of the proposed mechanistic pathways linking environmental agents to the development of ADs. Environmental agents are associated with the development of ADs in susceptible hosts. OS appears to be a common mechanism of many environmental agents that contribute to ADs. OS-mediated disturbance of nuclear factor erythroid 2-related factor 2 (Nrf2) and induction of NF-kB, Poly (ADP-ribose) polymerase 1 (PARP1), and NLR family pyrin domain containing 3 (NLRP3) can cause activation of both innate and adaptive immune systems, resulting in pro-inflammatory cytokines and production of autoantibodies, leading to tissue damage in ADs. Reactive oxygen species (ROS) and lipid peroxidation-derived reactive aldehydes (i.e., HNE and MDA) have the potential to cause protein medications and neoantigen formation, which will activate antigen presentation cells including dendritic cells (DCs) and macrophages (MΦ), that consequently promote activation of T and B cells.

Figure 2

The proposed link between gut dysbiosis and ADs in genetically susceptible individuals. Chemical-induced gut microbiome dysbiosis can alter intestinal barrier function, mucosal inflammation and immunity, resulting in increased translocation of bacteria, or its metabolites, such as circulating endotoxin lipopolysaccharides (LPS), thus promoting systemic aberrant auto-inflammatory responses, and eventually leading to ADs.