Biological effects / Functions & Short-Chain Fatty Acids (SCFAs)

Intestinal epithelial cells and immune cells take up Short-Chain Fatty Acids (SCFAs) through monocarboxylate transporters and/or sense SCFA signals via G protein-coupled receptors (GPCRs) on the cell surface.
Nagata et al. 2024 J Immunol 212(5): 771

Short-chain fatty acids (SCFAs) offer numerous health benefits: anti-inflammatory, immunoregulatory, antiobesity, antidiabetic, anticancer, cardiovascular protective, hepatoprotective, and neuroprotective effects.
Akhtar et al. 2022 Anim Nutr 8: 350-360
Xiong et al. 2022 Foods 11: 2863

The microbe-derived SCFAs are also an excellent energy source for epithelial and immune cells.
Zhang et al. 2022g Front. Cell Dev. Biol. 10: 874940

SCFAs can cross the gut epithelium to promote Immune tolerance by inducing the anti-inflammatory CD4+ CD25+ FOXP3+ Regulatory T Cells (Tregs) (peripherally induced) and stimulating the production of TGF-beta.
Zhang et al. 2022g Front. Cell Dev. Biol. 10: 874940

In addition, Short-chain fatty acids (SCFAs) also directly modulates host metabolic health through a range of tissue-specific (liver, adipose tissue, or skeletal muscle) mechanisms related to Appetite regulation, energy expenditure, glucose homeostasis, and immunomodulation
Blaak et al. 2020 Benefic. Microbes 11: 411-455
Li et al. 2021i Microorganisms 9: 1017

The individual SCFAs differ in their effects on health promotion and disease prevention.
Machate et al. 2020

||Significant increase|Significant decrease|Stable performance|
---|---|---
|SCFAs|Gram-positive bacteria|Gram-negative bacteria|Systemic health|
||Systemic health|pH intracellular & gut lumen||
||Immune system|Adipocyte lipolysis & adipogenesis||
||Adipocyte & Lipogenesis|IBD||
||Satiety|CVD, Colon cancer, Obesity, Diabetes||
||Cellular activation|||
|Acetate||Leptin stimulation|Process of de novo lipogenesis|
|||Pro-inflammatory cytokines|Cholesterol synthesis|
|||Free fatty acids to the liver|Bacteria growth|
||||Transforming propionate into glucose|
|Butyrate|Gut bacteria|Food intake|Cell proliferation|
||Apoptosis of colon cancer cells|Cancer & Adenoma|Gut hormone|
||Intestinal gluconeogenesis|||
||Epithelial cells to beta-oxidation|||
||Anti-inflammatory activity|||
|Propionate|Satiety|Cholesterol synthesis|Plasma fatty acids|
||Gut hormones|Food intake|Gluconeogenesis in the liver|
|||Colon cancer & Adenoma||
Machate et al. 2020

Short-Chain Fatty Acids (SCFAs) can influence the barrier integrity
Donia & Fischbach 2015 Science 349: 1254766
Thaiss et al. 2016 Nature 535: 65-74
Amabebe et al. 2020 British Journal of Nutrition 123: 1127-1137

There is an urgent need for well-controlled longer-term human Short-Chain Fatty Acids (SCFAs) intervention studies.
Blaak et al. 2020 Benefic. Microbes 11: 411-455

The effects of Short-Chain Fatty Acids (SCFAs) on promoting the growth of animals, increasing the length and height of intestinal villi, reducing fat gain, and inhibiting inflammation have been further confirmed
Wu et al. 2018 Plos One 13(5):e0197762
Oh et al. 2019a Sci Rep 9: 20300
Jia et al. 2020 Int Immunopharmacol 78: 106004

Emerging data show that Short-chain fatty acids (SCFAs) contribute to immune homeostasis in mucosa, although excessive and suboptimal levels of Short-chain fatty acids (SCFAs) are often associated with inflammation and Cancer / Tumors
Pandiyan et al. 2019 Front Immunol 10: 426

Short-Chain Fatty Acids (SCFAs) may play a role in the pathophysiology of obesity and related diseases such as type 2 diabetes mellitus by affecting body weight control through effects on energy intake and energy expenditure, as well as insulin sensitivity Canfora et al. 2015 Nature Reviews Endocrinology 11: 577-591
Chambers et al. 2015a Proc Nutr Soc 74: 328-36
Rios-Covian et al. 2016 Frontiers in Microbiology 7: 185
Chambers et al. 2018b Current Nutrition Reports 7: 198-206

Despite the expression of G-Protein Coupled Receptor 43 (GPR43) and G-Protein Coupled Receptor 41 (GPR41) in the Pancreatic Beta Cells, the roles of Short-Chain Fatty Acids (SCFAs) in directly modulating insulin secretion remain somewhat uncertain.
Brubaker 2018 Endocrinology 159: 2978-2979

A recent paper suggested that Roseburia intestinalis cooperates with dietary plant polysaccharides to produce butyrate .

This interaction impacts gene expression in the gut, exerts modulatory effects on metabolism, shifting it from glycolysis to fatty acid utilization (an effect often associated with anti-inflammatory cytokines and lower systemic inflammation), and finally ameliorates atherosclerosis in experimental models
Kasahara et al. 2018 Nat Microbiol 3:1461-1471

Short-Chain Fatty Acids (SCFAs) have been implicated in regulating intestinal epithelial cell growth, and differentiation and stimulation of the immune system among various other important biological processes
Kim et al. 2017 Immunol Rev. 279(1): 90-105

Short-chain fatty acids (SCFAs) such as butyric acid, propionic acid, and acetic acid are produced by colonic microbial fermentation of undigested or partially digested dietary fibers. They bind G protein-coupled receptors (GPCRs), such as GPR41, GPR43, and GPR109A, on the surface of epithelial cells and immune cells. Transport or diffusion of SCFAs into host cells results in their metabolism and/or inhibition of histone deacetylase (HDAC) activity. The effects of SCFAs are manifold and include enhanced epithelial barrier function and immune tolerance, which promote eubiosis by enhanced production of mucus by intestinal goblet cells, inhibition of NFKB, activation of inflammasomes, and subsequent production of interleukin-18 (IL-18), increased secretion of secretory IgA (sIgA) by B cells / B Lymphocytes, reduced expression of T cell-activating molecules on antigen-presenting cells, such as dendritic cells (DCs), and increased number and function of colonic regulatory T (Treg ) cells, including their expression of FOXP3 and their production of the Anti-inflammatory cytokines TGF-beta and IL-10. SCFAs also reach other organs, such as the brain and lungs, in which they directly or indirectly act on local or resident antigen-presenting cells to decrease inflammatory responses associated with neuroinflammation and allergic airway disease
Rooks & Garrett 2016 Nature Rev. Immunology 16: 341

Supplementing mice with butyrate and succinate results in improved glucose sensitivity. Butyrate enhances insulin sensitivity and boosts Energy expenditure in mice. The succinate produced by microbiota enhances glucose balance through the process of intestinal gluconeogenesis.
Gao et al. 2009 Diabetes 58: 1509-1517
De Vadder et al. 2016 Cell Metab 24: 151-157

Butyrate, together with other short-chain fatty acids (SCFAs) such as acetate and propionate, is generated through the fermentation of unabsorbed food components by the microbiota in the large intestine. This process provides several beneficial effects on the host, including enhanced gut barrier integrity, better glucose homeostasis, improved lipid metabolism, regulated appetite, and strengthened immune function.
Tan et al. 2014 Adv Immunol. 121: 91
Koh et al. 2016 Cell 165: 1332
Morrison & Preston 2016 Gut Microbes 7: 189-200

Increasing the colonic production of Short-Chain Fatty Acids (SCFAs) stimulates multiple hormonal and neural mechanisms that suppress appetite and energy intake (anorectic effect)
Chambers et al. 2015a Proc Nutr Soc 74: 328-36

Short-chain fatty acids (SCFAs) or metabolites produced by Clostridium tyrobutyricum or Bacteroides thetaiotaomicron decrease blood brain barrier permeability
Braniste et al. 2014 Sci. Transl. Med. 6: 263ra158

SCFAs have a range of effects on many cell types, including anti-inflammatory effects on myeloid cells and colonic regulatory T cells, with consequences for intratumoral inflammation
Arpaia et al. 2013 Nature 504: 451-455

SCFAs have been shown to reduce chemotaxis and cell adhesion; this effect is dependent on type and concentration of SCFA.
Meijer et al. 2010 Current opinion in clinical nutrition and metabolic care 13:715–721

Short-chain fatty acids (SCFAs) serve as the primary energy source for colonocytes
Guilloteau et al. 2010 Nutr. Res. Rev. 23: 366-384

A combination of the three SCFA causes a shift in the T helper lymphocyte phenotype towards a more anti-inflammatory phenotype and this might explain the protective effects of fiber. Acetate and propionate in combination were able to prevent the inhibitory effect of butyrate on IFN-gamma production. Acetate and propionate increased IFN-gamma production, whereas butyrate inhibited it
Cavaglieri et al. 2003

Acetate and propionate were able to partly prevent the inhibitory effect of butyrate on IL-2 production
Cavaglieri et al. 2003

SCFAs are energy sources for gastrointestinal mucosal cells . In particular, butyrate is the primary Energy source for colonocytes
Pryde et al. 2002 FEMS microbiology letters. 217: 133–139

see also:
Acetate & Biological effects / Functions
Butyrate / Butyric acid & Chemoprevention
Biological effects / Functions & Butyrate / Butyric acid
Biological effects / Functions & Propanoate Metabolism / Propionate / Propionic acid
Dietary Fibers (DF) & Short-chain Fatty Acids (SCFAs)
Energy Expenditure & Short-Chain Fatty Acids (SCFAs)
G-Protein Coupled Receptors (GPCRs) & Short-Chain Fatty Acids (SCFAs)
Gut microbiota & Short-Chain Fatty Acids (SCFAs)
Gut microbiota & Spatial Organization
Insulin Sensitivity & Short-Chain Fatty Acids (SCFAs)
Intestine / Gastrointestinal tract (Gut / GIT) & Prebiotics
Mode of action (MoA) & Short-Chain Fatty Acids (SCFAs)