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Méndez-Sánchez et al. Hepatoma Res 2020;6:5  I  http://dx.doi.org/10.20517/2394-5079.2019.29                             Page 5 of 13































               Figure 3. Composition of a “healthy” gut microbiota


               this layer. Similarly, Paneth cells secrete the derived regenerating islet (Reg) 3β in the mucus layer. These
               molecules are involved in gut homeostasis and exhibit antimicrobial activity that shapes the composition
                                        [22]
               of the intestinal microbiome . All these gut defense mechanisms are reinforced by numerous immune
               cells in the lamina propria that play an essential role in the protection of the intestinal mucosa against the
               invasion of bacteria. Of this large number of immune cells, it is worth highlighting T cells, mast cells, and
                                                         [23]
                                                                                                         +
               eosinophils due to their important contributions . First, T cells regulate cell permeability through Na /
               K  ATPase pumps, as well as the release of proinflammatory cytokines such as interferon-gamma (IFNγ),
                +
               tumor necrosis factor-alpha (TNF-α), and delta-positive intestinal intraepithelial lymphocytes (iIELγδ+),
               which are also found in the basolateral membrane of epithelial cells, involved in the maintenance of its
               function. Mast cells release different proinflammatory mediators such as histamine, leukotrienes, platelet-
               activating factor, and cytokines, with important immune-mediated functions throughout the entire
               GI tract. Ultimately, eosinophils increase intestinal permeability through different mediators such as
               histamine, prostaglandins, and TNF-α .
                                                [22]
               Composition of a “healthy” gut microbiota
               In the small intestine, food and nutrients absorption is mainly done in the duodenum through the release
               of digestive enzymes. At this site, food transit is faster, and the presence of oxygen limits bacterial density
                  3-4
               [10  Colony-forming unit (CFU)/mL]. Firmicutes and Actinobacteria predominate in this site with an
               important growth of Gram-positive aerobes and facultative anaerobes, including Lactobacilli, Enterococci,
                                                                                                  [25]
                                                                          3-7
               and Streptococci with a progressive increase in bacterial density (10  CFU/mL) in the jejunum . In the
               first part of the ileum, the bacterial density increases with a predominance of aerobic species (10  CFU/
                                                                                                    9
               mL). In contrast, the distal part of the ileum (near the ileocecal valve) is inhabited by anaerobes and
               Gram-negative microorganisms similar to those found in the colon (characterized by a slower transit and
               its anaerobic condition). In the colon, the number of anaerobes exceeds aerobes microorganisms with
               a bacterial density of 10  CFU/mL and an important predominance of Firmicutes and Bacteroidetes.
                                     12
               Moreover, in the GI lumen, Bacteroides, Bifidobacterium, Streptococcus, Enterobacteriaceae, Enterococcus,
               Clostridium, Lactobacillus and Ruminococcus spp. are the bacterial genera that predominate, while
               Clostridium, Lactobacillus, Enterococcus, and Akkermansia spp. are more frequent in the mucosa [Figure 3].
               In addition, some pathogenic bacteria including Campylobacter jejuni, Salmonella enterica, Vibrio cholera,
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