Use of Short-Chain Fatty Acids for the Recovery of the Intestinal Epithelial Barrier Affected by Bacterial Toxins

Abstract

Short-chain fatty acids (SCFAs) are carboxylic acids produced as a result of gut microbial anaerobic fermentation. They activate signaling cascades, acting as ligands of G-protein-coupled receptors, such as GPR41, GPR43, and GPR109A, that can modulate the inflammatory response and increase the intestinal barrier integrity by enhancing the tight junction proteins functions. These junctions, located in the most apical zone of epithelial cells, control the diffusion of ions, macromolecules, and the entry of microorganisms from the intestinal lumen into the tissues. In this sense, several enteric pathogens secrete diverse toxins that interrupt tight junction impermeability, allowing them to invade the intestinal tissue and to favor gastrointestinal colonization. It has been recently demonstrated that SCFAs inhibit the virulence of different enteric pathogens and have protective effects against bacterial colonization. Here, we present an overview of SCFAs production by gut microbiota and their effects on the recovery of intestinal barrier integrity during infections by microorganisms that affect tight junctions. These properties make them excellent candidates in the treatment of infectious diseases that cause damage to the intestinal epithelium.

Physicochemical properties and bioactivity of polysaccharides from Isaria cicadae Miquel with different extraction processes: effects on gut microbiota and immune response in mice

“…34 Furthermore, SCFAs act as ligands for G protein-coupled receptors, which could activate signaling cascades, regulate inflammatory responses and increase intestinal barrier integrity by enhancing the function of tight junction proteins. 58 In particular, butyrate has been shown to restore barrier function by positively regulating the expression of Claudin-1, ZO-1, and occludin in intestinal epithelial cells, resulting in increased transepithelial electrical resistance. 59 The intestinal barrier protects the host from gut microbes, food antigens, and endotoxins, which provide protection against metabolic, autoimmune, and aging-related diseases.…”

The Therapeutic Effect of SCFA-Mediated Regulation of the Intestinal Environment on Obesity

“…Researchers have found an increased number of white blood cells in the intestinal mucosal barrier, a shift to proinflammatory cell types (such as Th1 cells, total macrophages, dendritic cells, and natural killer (NK) cells) in obese people, and an increased incidence of colitis ( 6 , 29 , 30 ). Finally, it is well-known that an important feature of intestinal microbiota disorder is the decreased bacterial abundance of SCFA in the intestinal microbiota of obese patients, which leads to a decrease in SCFA levels and the occurrence of intestinal inflammation ( 31 ). SCFA, as key microbial metabolites that maintain the function of the intestinal epithelium, have been deeply studied regarding their ability to support intestinal barrier function ( Table 1 ).…”

“…SCFA-sensing G protein-coupled receptors (GPCRs), also known as free fatty acid receptors (FFARs), including GPR41 (FFAR3), GPR43 (FFAR2), and GPR109A, are mainly expressed by IECs, especially intestinal endocrine cells ( 31 , 62 , 63 ). They can be activated by SCFA and are highly expressed in the human intestinal mucosa, playing a key role in maintaining the homeostasis of intestinal barrier function.…”

Microbiomes in physiology: insights into 21st‐century global medical challenges

“…Through their interaction with GPCRs, SCFAs have been shown to modulate the secretion of hormones including glucagon‐like peptide‐1 and peptide YY, which impact on the brain functions such as mood, appetite, food intake and energy expenditure (Frost et al., 2014 ; Modasia et al., 2020 ). In the gut, SCFAs are also utilised by intestinal epithelial and colonic cells as energy sources, positively promoting gut barrier integrity, as well as maintaining low intestinal pH that is unfavourable to opportunistic pathogens and pathobionts (Pérez‐Reytor et al., 2021 ). Nevertheless, SCFAs may also be used by pathogens such as Salmonella , Clostridium and Citrobacter species as a cue for expressing virulence genes (Zhang et al., 2020 ).…”