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 pro- and 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.

Keywords: gut microbiota; inflammatory bowel disease; inflammatory diseases; macrophage; obesity.

FIGURE 1

Macrophages are involved in the interaction between gut microbiota and IBD or Obesity. (A) Under gut homeostasis, bone marrow derived Ly6C⁺ monocytes are constantly recruited to gut to replenish the intestinal macrophages (CD14^– macrophages) which recognize the pathogen through TLR4 receptor and secret anti-inflammatory cytokine IL-10 to promote Treg cell expansion. (B) In IBD, the inflammatory environment lead to gut dysbiosis included increased number of AIEC which can survive and replicate in macrophages, and decreased butyrate bacteria like Ruminococcaceae, Eubacterium, Clostridia, and Firmicutes, which impairs the ability of butyrate exert anti-inflammatory role through inhibiting HDACs/NF-κB (GPR43/41) or promoting IL-10 secretion (GPR109a). Additionally, blood Ly6C⁺ monocytes are recruited to intestinal to become inflammatory macrophages (CX3CR1⁺ macrophages) and secrete pro-inflammatory cytokines such as IL-23 and TNF-α to participated in inflammatory response. (C) In Obesity, the alteration of gut microbiota composition caused by HFD-diet lead to an increase of intestinal permeability, therefore LPS enter system circulation (i.e., metabolic endotoxemia). Adipose tissue macrophages are response to LPS activation and transform to M1 phenotype.