The Relationship Between Gut Microbiota and Inflammatory Diseases: The Role of Macrophages

Abstract

Gut microbiota, an integral part of the human body, comprise bacteria, fungi, archaea, and protozoa. There is consensus that the disruption of the gut microbiota (termed "gut dysbiosis") is influenced by host genetics, diet, antibiotics, and inflammation, and it is closely linked to the pathogenesis of inflammatory diseases, such as obesity and inflammatory bowel disease (IBD). Macrophages are the key players in the maintenance of tissue homeostasis by eliminating invading pathogens and exhibit extreme plasticity of their phenotypes, such as M1 or M2, which have been demonstrated to exert proand anti-inflammatory functions. Microbiota-derived metabolites, short-chain fatty acids (SCFAs) and Gram-negative bacterial lipopolysaccharides (LPS), exert anti-inflammatory or pro-inflammatory effects by acting on macrophages. Understanding the role of macrophages in gut microbiota-inflammation interactions might provide us a novel method for preventing and treating inflammatory diseases. In this review, we summarize the recent research on the relationship between gut microbiota and inflammation and discuss the important role of macrophages in this context.

Dual Carbonic Anhydrase IX/XII Inhibitors and Carbon Monoxide Releasing Molecules Modulate LPS-Mediated Inflammation in Mouse Macrophages

“…They express pattern recognition molecules, such as Toll-like Receptor (TLR) 4, to recognize foreign pathogens, remove toxic molecules, and protect against infection. The pro-inflammatory endotoxin or lipopolysaccharide (LPS) is produced by Gram-negative microorganisms and binds to TLR4, triggering the inflammation process [ 53 ]. In the present investigation, RAW 264.7 macrophages were stimulated with LPS 0.1 μg/mL to establish pro-inflammatory conditions in vitro.…”

Exploring the Triple Interaction between the Host Genome, the Epigenome, and the Gut Microbiome in Type 1 Diabetes

“…This was consistent with another study that indicated the immunoinhibitory properties of Bacteroides LPS, making it less effective in providing early life signals required to maintain mucosal homeostasis (and prevent inflammation) than other forms of LPS [ 101 , 103 ]. Interestingly, it is well known that the balance between the activation or suppression of the M1 or M2 macrophages can either enhance or terminate the auto-immune response in the gut which can be affected by the gut microbiome [ 106 ]. The low-grade intestinal inflammation in individuals with T1D was shown to enhance the polarization of the pancreatic macrophages into the M1 classically activated macrophages [ 107 ], in which the bacterial LPS acts as an activation signal affecting the classically activated M1 macrophages by interacting with its Toll-like receptor 4 (TLR4) receptor and inducing the phosphorylation of both STAT1α and STAT1β [ 108 ].…”

“…Furthermore, LPS affects the expression of the inflammatory genes by downregulating the expression of the ( P2Y(2)R ) G-protein-coupled which is necessary for TLR4 phosphorylation in macrophages, mediating the production of the pro-inflammatory cytokines and the type I interferon (IFN) [ 80 ]. These cytokines are involved in organizing the trafficking of autoreactive CD8 + T cells towards the islets which are associated with the initiation of T1D [ 88 , 106 , 108 , 109 , 110 , 111 ]. The dynamic role of the microbiota in modulating the immune system is well known [ 46 , 47 ].…”

“…This was associated with a significant increase in Firmicutes , Bacteroidetes , Ruminococcaceae , Proteobacteria , Akkermansia mucinophila , and Enterococcus that preceded the auto-immune response in T1D in SPF NOD mice [ 150 , 151 , 152 ], which further supports the role of the gut microbiota in the development and progression of T1D [ 73 , 151 ]. It is expected that the lack of a healthy gut microbiota affects the regulation and the maturation of the immune system [ 74 , 90 , 106 , 161 ]. This, in turn, leads to a deficiency in the development of mucosal-associated lymphoid tissue, specifically plasma cells and CD4 + T cells, and in turn promotes a differentiation imbalance between Th1, Th17 (T-helper cells), and Treg cells, which is associated with a higher rate of insulitis [ 151 ] as shown in Figure 1 .…”

Effects of Maresin 1 (MaR1) on Colonic Inflammation and Gut Dysbiosis in Diet-Induced Obese Mice

“…Obesity seems to aggravate the burden of inflammatory bowel disease in humans. However, the complex relationship between dysbiosis of gut microbiota and gut inflammation in bowel diseases still needs to be better elucidated in obese humans [11,12]. Dysbiosis is directly related to a higher intestinal permeability due to the epithelial barrier deterioration, increased lipopolysaccharide (LPS) levels in the circulation, small intestine bacterial overgrowth, tight junctions' alteration, and even the whole bacterial translocation, among others, causing endotoxemia, which can reach and damage the liver through the portal vein [13].…”