The Gut-Immune Axis | A Brief Review of Anatomy

The Gut-Immune Axis: Intestinal Barrier Focus

The intestinal barrier — in conjunction with the intestinal microbiome, immune status, and more — serves an integral role in regulating homeostasis along the "gut-immune axis." In briefly expanding upon the intestinal barrier: intestinal epithelial cells, intestinal mucus, tight junction proteins, and more work in concert, aiding in supporting intestinal barrier integrity both physically and chemically. Likewise, these physical and chemical barriers aid in preventing the unintended translocation of luminal antigens (1, 2, 3).

Intestinal Barrier Anatomy

The intestinal barrier separates the internal milieu of the intestinal lumen from the systemic environment of the body. From the innermost to the outermost layer, the intestinal wall is composed of the mucosa (It may be noted that the intestinal mucosa includes the epithelium, lamina propria, and muscularis mucosae.), the submucosa, the muscularis propria (It may be noted that the muscularis propria includes an inner circular muscle layer, intermuscular space, and an outer longitudinal muscle layer.), and the serosa (3, 4).

1. Mucus Layer: Intestinal mucus is located on the luminal surface of the intestinal epithelium, forming a protective gel-like barrier between the intestinal contents and the epithelial cells. Moreover, along the intestinal tract, the organization of the mucus barrier varies in relation to microbial density and functional requirements. In the small intestine, the mucus exists as a single layer that permits closer interaction between the epithelium and luminal contents. By contrast, the large intestine features a more elaborate, two-tiered mucus organization—comprising a dense, inner layer that remains largely free of bacteria, and a looser outer layer that interfaces with the resident microbial community (4).

2. Intestinal Epithelium: The intestinal epithelium is located beneath the intestinal mucus and is composed of a single layer of epithelial cells including enterocytes, goblet cells, enteroendocrine cells, and paneth cells (3, 4). Moreover, tight junctions are composed of various proteins that aid in "sealing" the spaces between adjacent epithelial cells. The primary transmembrane proteins involved are claudins, occludin, tricellulin, and junctional adhesion molecule (JAM) (5). Likewise, zonula occludens proteins act as scaffolding bridges that link transmembrane tight-junction proteins to the actin cytoskeleton (5). Tight junctions play a role in maintaining the selective permeability of the epithelial barrier, aiding in regulating the paracellular passage (It may be noted that "paracellular" refers to passage which is between epithelial cells.) of ions, water, and other molecules.

3. Lamina Propria: The lamina propria, beneath the epithelium, is rich in connective tissue, blood vessels, lymphatics, and a diverse array of immune cells including T cells, B cells, macrophages, dendritic cells, and more (6). Likewise, these cells play a central role in mucosal immune defense, and it may be noted that the mucosal immune system must maintain a delicate balance between responsiveness and tolerance. When this regulation becomes disrupted, immune reactions to commensal microorganisms or dietary components can contribute to inflammation and tissue stress within the intestinal environment (6).

The Intestinal Microbiome & The Gut-Immune Axis

The gut microbiota contributes to the development of the intestinal immune system and, likewise, plays an important role in immune tolerance (7). Moreover, both the innate and adaptive immune systems aid in regulating microbial balance, helping sustain stability between commensal and potentially pathogenic species. Through this reciprocity, the gut microbiota and the host immune system function in concert to maintain immune homeostasis (7).

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There are several mechanisms through which the intestinal microbiome has an effect on immune health. Likewise, this relationship can be regarded as bidirectional, as immune function aids in regulating the intestinal microbiome (7).

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