Review Article

Review Article: Dietary Fibre in the era of Microbiome Science

John O'Grady; Eibhlís M. O'Connor; Fergus Shanahan

Disclosures

Aliment Pharmacol Ther. 2019;49(5):506-515. 

In This Article

Biologic Effects of Dietary Fibre and end Products of Fibre Metabolism

The action of fibre depends on solubility, viscosity and fermentation. Viscosity influences chyme consistency, digestion, absorption and satiety.[22,23] These effects are associated with reduced intake and offer therapeutic value in the management of obesity and related complications including the metabolic syndrome.[23] Viscous fibres, such as psyllium, delay degradation and absorption of nutrients can reduce total glucose and cholesterol absorption by up to 12%.[24,25] Nutrients then reach the distal small bowel, where the mucosal response includes release of glucagon-like peptide-1 (GLP-1). The result is decreased appetite, decreased glucagon secretion, improved insulin sensitivity and delayed gastric emptying (the "ileal brake" phenomenon),[13] thereby improving glycaemic control. In addition, fibre plays a role in nutrient bioavailability as it binds ions such as copper, calcium and zinc, which are released in the distal gut as fibre is fermented, where these ions exert effects such as local anti-microbial action.[10]

Fermentation of fibre by gut microbiota yields SCFAs that provide energy for the host, but also exert an immunoregulatory and gut-brain signalling role (Figure 3).[26,27,28,29,30,31] The primary SCFAs produced from fibre fermentation are acetate (C2), propionate (C3) and butyrate (C4).[27,28,29,30,31,32] Acetate is produced from pyruvate via acetyl-CoA or via the Wood-Ljungdahl pathway. Propionate is produced from succinate conversion to methylmalonyl-CoA via the succinate pathway and is also synthesised from acrylate, with lactate as a precursor, through the acrylate pathway or the propanediol pathway. Butyrate is formed first by condensation of two molecules of acetyl-CoA and reduction to butyryl-CoA, which can be converted to butyrate either by the butyryl-CoA: acetate CoA-transferase route or via butyrate kinase and phosphotransbutyrylase.[33,34] Acetate is the most abundant SCFA detectable in human peripheral circulation, as propionate is metabolised by the liver and butyrate is the primary source of energy used by colonocytes.[33]

Figure 3.

Complexity of diet-microbe-host interaction illustrated with example of short chain fatty acids (SCFAs). Microbial fermentation of fibre produces SCFAs; acetate, propionate and butyrate, which have influences on microbial, metabolic and immune homeostasis. Butyrate and propionate inhibit histone deacetylases (HDAC) to allow ongoing chromatin gene expression via acetylation with anti-inflammatory and immune effects. SCFAs activate GP109A, GPR41 and GPR43 (GPCR) with immune system influences including increased IL-18, regulatory T cells (Tregs), IL-10 producing T cells and activation of the NLRP3 inflammasome. Lipid and glucose Metabolism is altered through GPCR mediated hormone activation including peptide YY and GLP-1 as well as GPR41/43 receptors on white adipose tissue (WAT). SCFA, Short chain fatty acid; GPCR, G-protein coupled receptors; IL-18, interleukin-18; IL-10, interleukin-10; Peptide YY, peptide tyrosine; GLP-1, glucagon like peptide-1; HAT, histone acetyltransferase; HDAC, histone deacetylase

Butyrate and, to a lesser extent, propionate are known to act as histone deacetylases (HDAC) inhibitors. Histone acetylation increases accessibility of the transcriptional machinery to promote gene transcription; acetyl groups are added to histone tails by histone acetyltransferases (HATs) and are removed by HDAC. HDAC inhibition exerts anti-inflammatory and immune effects through suppression of pro-inflammatory macrophage responses and differentiation of dendritic cells from bone marrow stem cells as well as regulating cytokine expression in T cells and generation of regulatory T cells (Tregs).[33]

Further immune effects occur via G-protein coupled receptor (GPCR) signalling. Butyrate-stimulated signalling of GPR109A and GPR43 (GPCRs) increases generation of Tregs, interleukin (IL)-10-producing T cells and IL-18 secretion by intestinal epithelial cells,[35] while also activating NLRP3 inflammasome, which is critical for intestinal homeostasis.[33,36] This attenuates the inflammatory response, through release of IL-18, of the mucosal immune system to gut commensal microbes and promotes gut barrier integrity.[33,37] Fibre-rich diets, in animal studies, are also associated with increased mucosal thickness and reduced permeability in the gut, which improves mucus layer function and reduces bacterial translocation and infection.[38,39,40]

GPR41 and GPR43 appear to have important roles in metabolic homeostasis as well as immune function. Acetate and propionate are potent activators of these GPCRs.[33] GPR43 promotes GLP-1 secretion in the intestine, as well as regulating energy uptake in white adipose tissue (WAT) outside the gut.[33,41] In animal models, GPR43 over-expression is associated with leaner mice,[41] whereas GPR41 is associated with microbial-induced adiposity.[33] GPR41−/− knock-out mice are leaner than wild-type counterparts, though this association does not occur under germ-free conditions.[42] Peptide YY production via microbial and SCFA signalling also occurs in a GPR41 dependent fashion and has a role in delaying gut motility and prolonging nutrient absorptive capacity.[42] Further metabolic functions include increased insulin sensitivity and glucose tolerance via gut-brain neural signalling, induced by propionate and butyrate mediated de-novo glucose synthesis in gut epithelium.[33] Thus, SCFA signalling of GPCRs, in animal models, appears to have clear metabolic influences and specific effects in humans are worth exploring.[33]

Potentially substantial end points in fibre metabolism and fermentation in humans due to described SCFA-induced immunoregulatory and anti-inflammatory influences may offer new targets in fibre-related health outcomes. This is in addition to the metabolic benefits of various soluble and viscous fibres. Current described biological effects of individual fibre components and sources of these fibres, are summarised in Table 1.

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