Gut Barrier Damage and Gut Translocation of Pathogen Molecules in Lupus, an Impact of Innate Immunity (Macrophages and Neutrophils) in Autoimmune Disease

Abstract

The gut barrier is a single cell layer that separates gut micro-organisms from the host, and gut permeability defects result in the translocation of microbial molecules from the gut into the blood. Despite the silent clinical manifestation, gut translocation of microbial molecules can induce systemic inflammation that might be an endogenous exacerbating factor of systemic lupus erythematosus. In contrast, circulatory immune-complex deposition and the effect of medications on the gut, an organ with an extremely large surface area, of patients with active lupus might cause gut translocation of microbial molecules, which worsens lupus severity. Likewise, the imbalance of gut microbiota may initiate lupus and/or interfere with gut integrity which results in microbial translocation and lupus exacerbation. Moreover, immune hyper-responsiveness of innate immune cells (macrophages and neutrophils) is demonstrated in a lupus model from the loss of inhibitory Fc gamma receptor IIb (FcgRIIb), which induces prominent responses through the cross-link between activating-FcgRs and innate immune receptors. The immune hyper-responsiveness can cause cell death, especially apoptosis and neutrophil extracellular traps (NETosis), which possibly exacerbates lupus, partly through the enhanced exposure of the self-antigens. Leaky gut monitoring and treatments (such as probiotics) might be beneficial in lupus. Here, we discuss the current information on leaky gut in lupus.

The Regulatory Roles of Ezh2 in Response to Lipopolysaccharide (LPS) in Macrophages and Mice with Conditional Ezh2 Deletion with LysM-Cre System

“…The presence of lipopolysaccharide (LPS), a microbial molecule from Gram-negative bacteria, in blood has been clinically demonstrated as endotoxemia in several conditions, including sepsis [ 55 , 56 , 57 ], partly through gut barrier damage [ 1 , 22 , 24 , 58 ]. The activation of macrophages by LPS is possibly important in sepsis because macrophages are the innate immune cells responsible for the recognition of foreign molecules [ 51 , 59 ]. Among several alterations in LPS-stimulated macrophages, the epigenetic modifications, especially DNA methylation at the cytosine-phosphate-guanine (CpG) sites and the methylation at the N-terminal tails of histones, are critical regulators of chromatin structure that determine gene expression for responses, differentiation, and proliferation [ 60 ].…”

The leaky gut and the gut microbiome in sepsis – targets in research and treatment

“…The importance of PAMPs in sepsis implicates the gastrointestinal tract as an endogenous reservoir of several groups of organisms, including prokaryotes, i.e., bacteria and archaea, eukaryotes, i.e., fungi, and viruses, mostly bacteriophages, which are jointly referred to as ‘gut microbiota’. These organisms are separated from the host by only a single layer of enterocytes containing tight junction molecules [ 14 , 15 ]. During sepsis, enterocytes experience hyperpermeability caused by several factors, including intestinal hypoperfusion, enterocyte apoptosis, a systemic cytokine storm, and gut dysbiosis, which could promote the translocation of microbial molecules from the gut into systemic circulation.…”

Lacticaseibacillus rhamnosus dfa1 Attenuate Cecal Ligation-Induced Systemic Inflammation through the Interference in Gut Dysbiosis, Leaky Gut, and Enterocytic Cell Energy

“…As such, gut dysbiosis is an imbalance of gut microbiota (gut normal flora) correlating with unhealthy outcomes, that is affected by alterations in the intra-intestinal lumen and in the systemic situation [ 6 ]. For the intra-intestinal factors, increased gut pathogens, some diets, antibiotics, and the local inflammation (infection or non-infection) [ 7 , 8 , 9 , 10 ] induce gut dysbiosis, in part, through the enhanced intestinal immune cells that might have a different impact on different groups of gut organisms causing selective growth in some groups of bacteria (dysbiosis) [ 11 , 12 , 13 , 14 ].…”