Diet and microbiome in the beginning of the sequence of gut inflammation

Figure 1 Commensal microbiota modulates the response of the immune system in the intestinal mucosa and participates in the metabolism of the epithelium. A: In the case of immune regulation, dendritic cells (DCs), activated in M cells, modulate regulatory T lymphocytes (Tregs) through anti-inflammatory signals (such as interleukin [IL]-10), which in turn inhibit other anti-inflammatory signals (such as IL-10 and transforming growth factor-beta [TGFβ]) of T helper cells 1-17 and macrophages. In the case of epithelial metabolism, the synthesis of short chain fatty acids (SCFAs), the secretion of prostaglandins (PGEs, such as PGE2) and the activity of nuclear factor-kappa B (NF-kB) contributes to an adequate secretion of defensins α and β, to the appropriate functioning of the mucus layer and even the microbiome state in homeostasis; B: The persistence of bacteria adhering to a deteriorated mucus film, the decrease in defensins and the invasion of the epithelium produces the activation of DCs and macrophages, that in turn activate the T helper (Th) cells, Th1 and Th17, by proinflammatory signals (IL-1, IL-6, IL-12, and IL-23), thereby promoting a low apoptosis, clonal expansion with loss of response to anti-inflammatory signals, and contributing to tissue damage mediated by interferon gamma (INFγ) and tumor necrosis factor alpha (TNFα). This figure is based upon data published in Reference 11.

Figure 2 Metabolic epithelial changes in dysbiosis due to loss of obligate anaerobes. A: The eubiosis microbiome contains a significant number of obligate anaerobes that convert dietary fiber into short chain fatty acids (SCFAs), contributing to a C2-type epithelial trophism with high oxygen consumption (O₂), which limits its diffusion to the intestinal lumen and maintains the epithelium in relative hypoxia; B: The deterioration of the microbiome with loss of obligate anaerobes and SCFAs orients the metabolism of the epithelium to a C1-type, with greater glucose fermentation, low O₂ consumption, and generation of lactic acid and nitric oxide (NO). The higher partial pressure of the O₂ not consumed by the C1 colonocytes and the conversion of NO to nitrate (NO₃^-) causes an overgrowth of facultative anaerobes; C: The persistence of the loss of strict anaerobes and their fermentation products ends up causing epithelial damage (via polymorphonuclear neutrophils R-spondin 2), the response of which is crypt hyperplasia and the multiplication of stem cells (SCs). The sustained increase in NO₃^- and O₂ contributes to the persistence of facultative anaerobes and dysbiosis. This figure is based upon data published in reference 39.