Intestinal barrier and gut microbiota: Shaping our immune responses throughout life

Abstract

The gastrointestinal (GI) tract is considered the largest immunological organ in the body having a central role in regulating immune homeostasis. Contrary to earlier belief, the intestinal epithelial barrier is not a static physical barrier but rather strongly interacts with the gut microbiome and cells of the immune system. This intense communication between epithelial cells, immune cells and microbiome will shape specific immune responses to antigens, balancing tolerance and effector immune functions. Recent studies indicate that composition of the gut microbiome affects immune system development and modulates immune mediators, which in turn affect the intestinal barrier. Moreover, dysbiosis may favor intestinal barrier disruption and could be related to increased susceptibility to certain diseases. This review will be focused on the development of the intestinal barrier and its function in host immune defense and how gut microbiome composition throughout life can affect this role.

Keywords: ageing; development; gut immunity; microbiota; mucosal barriers.

Figures

Figure 1.

Schematic representation of mucosa, villi, crypts of Lieberkühn and cells of the small intestine. The intestinal lining of the lower intestine is highly folded to maximize absorption and contains finger-like mucosal projections that form structures called villi, in between the villi downward invaginations, called crypts of Lieberkuhn, extend down to the muscularis mucosae. Underlying the epithelium, the lamina propria, harbors dendritic cells, important antigen-presenting cells, which regulate humoral and cellular gut immunity. The muscularis externa layer contains two layers of smooth muscle that enable continuous peristaltic activity of the small intestine. On the left, the epithelium of a crypt and part of a villus are represented and different epithelial cells can be identified: enterocytes, tall columnar absorptive cells with ‘brush-like border’ on the apical surface, called microvilli; goblet cells, which secrete mucin, for lubrication of the intestinal contents and protection of the epithelium; enteroendocrine cells that secrete various gut hormones; stem cells that lie near the base of the crypt and give rise to the specialized epithelial cells; above the stem cells are transit amplifying cells; and Paneth cells, which have a defensive function secreting antimicrobial molecules into the lumen.

Figure 2.

Changes in human microbiota throughout life. The uterus is not a sterile environment, studies have found bacteria in placentae, fetal membranes, umbilical cord blood and meconium. Colonization of the infant gut will depend on the mode of birth, vaginally-delivered and Cesarean section (C-section) children acquire distinct bacterial communities. In young children, the composition of the gut microbiota often varies, is very diverse and less stable, with age gut microbiota becomes more stable. In old age, the gut microbiota alters, it is less diverse compared to younger age and presents reduction in short chain fatty acid-producing bacteria and increase in gram-negative LPS-secreting bacteria.,144