A Cross-Talk Between Microbiota-Derived Short-Chain Fatty Acids and the Host Mucosal Immune System Regulates Intestinal Homeostasis and Inflammatory Bowel Disease

Abstract

Gut microbiota has a fundamental role in the energy homeostasis of the host and is essential for proper "education" of the immune system. Intestinal microbial communities are able to ferment dietary fiber releasing short-chain fatty acids (SCFAs). The SCFAs, particularly butyrate (BT), regulate innate and adaptive immune cell generation, trafficing, and function. For example, BT has an anti-inflammatory effect by inhibiting the recruitment and proinflammatory activity of neutrophils, macrophages, dendritic cells, and effector T cells and by increasing the number and activity of regulatory T cells. Gut microbial dysbiosis, ie, a microbial community imbalance, has been suggested to play a role in the development of inflammatory bowel disease (IBD). The relationship between dysbiosis and IBD has been difficult to prove, especially in humans, and is probably complex and dynamic, rather than one of a simple cause and effect relationship. However, IBD patients have dysbiosis with reduced numbers of SCFAs-producing bacteria and reduced BT concentration that is linked to a marked increase in the number of proinflammatory immune cells in the gut mucosa of these patients. Thus, microbial dysbiosis and reduced BT concentration may be a factor in the emergence and severity of IBD. Understanding the relationship between microbial dysbiosis and reduced BT concentration to IBD may lead to novel therapeutic interventions.

Alterations in the gut microbiota and metabolite profiles of thyroid carcinoma patients

“…The abundance of Bacteroides , Megamonas and Lachnospiraceae genera was decreased in TC patients; these genera are known to benefit from participating in carbohydrate fermentation into SCFAs . Decreased levels of SCFA lead to increased colonocyte death and increased cell turnover and may partially explain the 3.two‐fold higher lifetime risk of CRC observed in patients with Crohn's disease (CD) .…”

“…24 The abundance of Bacteroides, Megamonas and Lachnospiraceae genera was decreased in TC patients; these genera are known to benefit from participating in carbohydrate fermentation into SCFAs. 48,49 Decreased levels of SCFA lead to increased colonocyte death and increased cell turnover and may partially explain the 3.two-fold higher lifetime risk of CRC observed in patients with Crohn's disease (CD). 50 However, propionic acid and butyric acid were not identified in our fecal metabolomics study, likely due to the inability to detect low concentrations or metabolite detection platform is unsuitable.…”

Gut Dysbacteriosis Is Associated with an Imbalanced Cytokines Network in Women with Unexplained Miscarriage

“…Moreover, a decrease in Prevotella and Prevotellaceae may cause a degeneration in the abundance of SCFAs, particularly butyrate, which can serve as the energy substrates for epithelial cells of the gut [42]. Thus, a decrease in Prevotella and Prevotellaceae leads to the reduction of inducible regulatory T cells (iTregs) and activation of proinflammatory cells [43,44]. The negative correlation between the decreased abundance of Prevotella_1, Prevotellaceae_UCG_003 and serum levels of IL-17A found in our study provide further evidence for this association.…”

Current understanding of the role of gut dysbiosis in type 1 diabetes

“…Prebiotics are non‐digestible carbohydrates that are resistant to the action of hydrolytic enzymes but can be metabolized by the gut microbiota, and their fermentation products, mainly SCFAs, beneficially affect the host . Short‐chain fatty acids resulting from the breakdown of different types of prebiotics maintain the integrity of all components of the gut barrier . Moreover, a reduction in SCFA‐producing bacteria was noted in T1D at the time of onset of autoimmunity, which was associated with impaired gut barrier functions .…”

“…130 Short-chain fatty acids resulting from the breakdown of different types of prebiotics maintain the integrity of all components of the gut barrier. 131 Moreover, a reduction in SCFA-producing bacteria was noted in T1D at the time of onset of autoimmunity, which was associated with impaired gut barrier functions. 132,133 Dietary intake of 1% authentic HMOs during early life for a period of 6 weeks delayed T1D development in NOD mice.…”