The interaction among gut microbes, the intestinal barrier and short chain fatty acids

Abstract

The mammalian gut is inhabited by a massive and complicated microbial community, in which the host achieves a stable symbiotic environment through the interdependence, coordination, reciprocal constraints and participation in an immune response. The interaction between the host gut and the microbiota is essential for maintaining and achieving the homeostasis of the organism. Consequently, gut homeostasis is pivotal in safeguarding the growth and development and potential productive performance of the host. As metabolites of microorganisms, short chain fatty acids are not only the preferred energy metabolic feedstock for host intestinal epithelial cells, but also exert vital effects on antioxidants and the regulation of intestinal community homeostasis. Herein, we summarize the effects of intestinal microorganisms on the host gut and the mechanisms of action of short chain fatty acids on the four intestinal barriers of the organism, which will shed light on the manipulation of the intestinal community to achieve precise nutrition for specific individuals and provide a novel perspective for the prevention and treatment of diseases.

Keywords: Gut microbiota; Interaction mechanism; Intestinal barrier; Intestinal epithelium cells; Short chain fatty acids.

Fig. 1

Composition and functions of intestinal microorganisms. With the advanced study of gut microorganisms, scholars have observed diverse roles of gut microorganisms, including involvement in neuroimmunomodulation, organism metabolism (lipid and bile acids), the synthesis of DNA and vitamins. Moreover, the fermentation products of microorganisms could modulate receptors and make a substantial contribution to the development of clinical drugs. However, the colonization of gut microbes is primarily influenced by changes in diet, environment, and nutrient composition. Source: Chénard et al., (2020); Gao et al., (2018); Filosa et al., (2018); Schoeler and Caesar (2019); Molinaro et al., 2018; Zeng et al., (2019); Pan et al., (2018); Biesalski (2016); Huang et al., (2019); Mu et al., (2015); Li et al., (2015); Feng et al., (2020); Conlon et al., (2015); Strandwitz (2018).

Fig. 2

The synthesis pathways of short-chain fatty acids (SCFA) and the primary role in carbohydrate and lipid metabolism. The microbial transformation of dietary fiber in the hindgut leads to the synthesis of the SCFA (mainly acetate, propionate and butyrate). The acetate is produced from pyruvate by the acetyl-coenzyme A (CoA) or W-L pathway. Propionate is formed from deoxyhexose via the propanediol pathway or from phosphoenolpyruvate via the succinate pathway or the acrylate pathway. Butyric acid is produced by synthesizing two molecules of acetyl-CoA to yield acetyl-CoA, then converted to butyryl-CoA by β-hydroxybutyryl-CoA and crotonyl-CoA. PST = phosphotransacetylase; AK = acetokinase; W-L = Wood-Ljungdahl; ME-COA = methylmalonyl-CoA; PO = pyruvic oxidase; PT = phosphotransferase; BK = butyrate kinase; TCA = tricarboxylic acid cycle; MVA = mevalonic acid; β-HBA = β-hydroxybutyric acid; HMG-CoA = β-hydroxy-β-methylglutaryl-coenzyme A. Source: Ragsdale and Pierce (2008); Hetzel et al. (2003); Scott et al. (2006); Louis et al. (2004); Duncan et al. (2002).

Fig. 3

Main effects of short-chain fatty acids (SCFA) on the mechanism barrier. SCFA protect the integrity of the mechanical barrier by enhancing the gene expression of intestinal tight junction proteins Occludin, zonula occludens (ZO), and claudins to promote contraction of tight junctions, desmosomes, and gap junctions, and reduce diarrhea by decreasing intestinal permeability. JAM = junctional adhesion molecule. Source: Ma et al. (2012); Tong et al. (2016); Slifer and Blikslager (2020); Huang et al. (2015).

Fig. 4

Main effects of short-chain fatty acids (SCFA) on the microbial barrier. SCFA protonate with the lipopolysaccharide carboxyl and phosphate groups of the bacterial outer membrane from the posterior, which weakens the defence of the bacterial outer membrane and undergoes dissociation, leading to disruption of cellular integrity. The COOH⁻ generated by SCFA dissociation also causes an imbalance of osmotic pressure inside the bacteria. Furthermore, SCFA could achieve bacterial inhibition by interfering with bacterial DNA and protein synthesis processes as well as triggering the host cell to produce the antimicrobial peptide. Source: Alakomi et al. (2000); Brul and Coote (1999); McLaggan et al. (1994); Roe et al. (1998); Alakomi et al. (2000); Rasch (2002); Roe et al. (2002); Jakubowski (2019).

Fig. 5

Main effects of short-chain fatty acids (SCFA) on the chemical barrier. SCFA activate inflammatory vesicles in IEC, promote the production of anti-inflammatory factors, upregulate the gene expression of mucin-1 (MUC1), MUC2, MUC3 and MUC4 in the intestine. SCFA could trigger the secretion of α-defensins or certain antimicrobial peptides from small intestine Paneth cells to finish the inhibition of foreign pathogens. Source: Singh et al. (2014); Sun et al. (2017); Takakuwa et al., (2019).

Fig. 6

Main effects of short-chain fatty acids (SCFA) on the immune barrier. SCFA protect the intestinal immune barrier by lowering the levels of tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ) and interleukin (IL)-6, activating the expression of G-protein coupled receptors (GPCR) to participate in the intestinal-mediated inflammatory and immune response, inhibiting the lipopolysaccharide-induced activation of nuclear factor kappa B (NF-κB), promoting potassium ion (K⁺) efflux and hyperpolarization in intestinal epithelium cells (IEC) as well as IL-18 formation, suppressing histone deacetylase (HDAC) and downregulating the expression of pro-inflammatory cytokines. Moreover, SCFA could improve the intestinal integrity by inhibiting the Toll-like receptor 4 (TLR4) signalling pathway. Source: Wang et al. (2018); Kim (2018); D'Souza et al. (2017); Thangaraju et al. (2009); Macia et al. (2015); Li et al. (2018b); Rooks and Garrett (2016); Wen et al. (2012); Hayashi et al. (2013); Wu et al. (2017).