Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism - PubMed (original) (raw)
Review
Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism
Douglas J Morrison et al. Gut Microbes. 2016.
Abstract
The formation of SCFA is the result of a complex interplay between diet and the gut microbiota within the gut lumen environment. The discovery of receptors, across a range of cell and tissue types for which short chain fatty acids SCFA appear to be the natural ligands, has led to increased interest in SCFA as signaling molecules between the gut microbiota and the host. SCFA represent the major carbon flux from the diet through the gut microbiota to the host and evidence is emerging for a regulatory role of SCFA in local, intermediary and peripheral metabolism. However, a lack of well-designed and controlled human studies has hampered our understanding of the significance of SCFA in human metabolic health. This review aims to pull together recent findings on the role of SCFA in human metabolism to highlight the multi-faceted role of SCFA on different metabolic systems.
Keywords: glucose homeostasis; gut microbiota; host metabolic health; inflammation; short chain fatty acids.
Figures
Figure 1.
The gut lumen is the major site of production but the concentration gradient falls from the lumen to the periphery with selective uptake of butyrate at the epithelium, propionate at the liver and acetate in the periphery. The significance for host physiology of this biological gradient is poorly understood.
Figure 2.
SCFA along with other metabolites entering the hepatic portal system are rapidly transported to the liver. The role of molecular signaling on different liver cell types is poorly characterized. SCFA can act on resident macrophages and hepatocytes although there may be functional selectivity for each SCFA. Incretion hormones may also act on hepatocytes and peripheral tissues. The overall impact of this dual signaling system appears to be maintenance of a healthy liver through regulation of hepatic metabolism and inflammation and control of adipose derived FFA flux. The peripheral effects of SCFA appear tissue specific. SCFA can regulate insulin in the pancreas, FFA flux from adipocytes, appetite centers in the brain and provide a fuel for the muscle. This multi-faceted role however, requires further investigation with well-designed and controlled studies in humans.
Similar articles
- Short-chain fatty acids in control of body weight and insulin sensitivity.
Canfora EE, Jocken JW, Blaak EE. Canfora EE, et al. Nat Rev Endocrinol. 2015 Oct;11(10):577-91. doi: 10.1038/nrendo.2015.128. Epub 2015 Aug 11. Nat Rev Endocrinol. 2015. PMID: 26260141 Review. - Short chain fatty acids in human gut and metabolic health.
Blaak EE, Canfora EE, Theis S, Frost G, Groen AK, Mithieux G, Nauta A, Scott K, Stahl B, van Harsselaar J, van Tol R, Vaughan EE, Verbeke K. Blaak EE, et al. Benef Microbes. 2020 Sep 1;11(5):411-455. doi: 10.3920/BM2020.0057. Epub 2020 Aug 31. Benef Microbes. 2020. PMID: 32865024 Review. - The role of short-chain fatty acids in the interplay between gut microbiota and diet in cardio-metabolic health.
Nogal A, Valdes AM, Menni C. Nogal A, et al. Gut Microbes. 2021 Jan-Dec;13(1):1-24. doi: 10.1080/19490976.2021.1897212. Gut Microbes. 2021. PMID: 33764858 Free PMC article. Review. - Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls.
Unger MM, Spiegel J, Dillmann KU, Grundmann D, Philippeit H, Bürmann J, Faßbender K, Schwiertz A, Schäfer KH. Unger MM, et al. Parkinsonism Relat Disord. 2016 Nov;32:66-72. doi: 10.1016/j.parkreldis.2016.08.019. Epub 2016 Aug 26. Parkinsonism Relat Disord. 2016. PMID: 27591074 - Impact of Glycosidic Bond Configuration on Short Chain Fatty Acid Production from Model Fermentable Carbohydrates by the Human Gut Microbiota.
Harris HC, Edwards CA, Morrison DJ. Harris HC, et al. Nutrients. 2017 Jan 1;9(1):26. doi: 10.3390/nu9010026. Nutrients. 2017. PMID: 28045429 Free PMC article.
Cited by
- Gut microbiota modulates depressive-like behaviors induced by chronic ethanol exposure through short-chain fatty acids.
Shen H, Zhang C, Zhang Q, Lv Q, Liu H, Yuan H, Wang C, Meng F, Guo Y, Pei J, Yu C, Tie J, Chen X, Yu H, Zhang G, Wang X. Shen H, et al. J Neuroinflammation. 2024 Nov 6;21(1):290. doi: 10.1186/s12974-024-03282-6. J Neuroinflammation. 2024. PMID: 39508236 - Engineering Probiotics for Diabetes Management: Advances, Challenges, and Future Directions in Translational Microbiology.
Zhang S, Ma J, Ma Y, Yi J, Wang B, Wang H, Yang Q, Zhang K, Yan X, Sun D, You J. Zhang S, et al. Int J Nanomedicine. 2024 Oct 28;19:10917-10940. doi: 10.2147/IJN.S492651. eCollection 2024. Int J Nanomedicine. 2024. PMID: 39493275 Free PMC article. Review. - Research on preventive effect of _Akkermansia muciniphila_AKK PROBIO on acute gouty arthritis in mice.
Ma X, Zhu N, Yu X, Wang W, Wu W. Ma X, et al. Food Sci Nutr. 2024 Aug 1;12(10):7644-7656. doi: 10.1002/fsn3.4367. eCollection 2024 Oct. Food Sci Nutr. 2024. PMID: 39479687 Free PMC article. - Gut microbiota and metabolic profile changes unveil the deterioration of alveolar bone inflammatory resorption with aging induced by D-galactose.
Liu F, Yao Y, Huang Y, Luo L, Wang Q, Chen B, Hu H. Liu F, et al. Sci Rep. 2024 Oct 30;14(1):26135. doi: 10.1038/s41598-024-75941-w. Sci Rep. 2024. PMID: 39477973 Free PMC article. - The Interplay of Inflammatory Bowel Disease (IBD) and Diabetes in Pediatrics: A Systematic Review.
Muhammad AFSS, Abdulkareem TMK, Alharbi AEB, Alessa NA, Bin Qaed S, Ebrahim EK, Zurayyir EJ, Alqasem MAS, Aamir J. Muhammad AFSS, et al. Cureus. 2024 Sep 29;16(9):e70425. doi: 10.7759/cureus.70425. eCollection 2024 Sep. Cureus. 2024. PMID: 39473672 Free PMC article. Review.
References
- Le Poul E, Loison C, Struyf S, Springael JY, Lannoy V, Decobecq ME, Brezillon S, Dupriez V, Vassart G, Van Damme J, et al.. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem 2003; 278:25481-9; PMID:12711604; http://dx.doi.org/10.1074/jbc.M301403200 - DOI - PubMed
- Brown AJ, Goldsworthy SM, Barnes AA, Eilert MM, Tcheang L, Daniels D, Muir AI, Wigglesworth MJ, Kinghorn I, Fraser NJ, et al.. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 2003; 278:11312-9; PMID:12496283; http://dx.doi.org/10.1074/jbc.M211609200 - DOI - PubMed
- Nilsson NE, Kotarsky K, Owman C, Olde B. Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids. Biochem Biophys Res Commun 2003; 303:1047-52; PMID:12684041; http://dx.doi.org/10.1016/S0006-291X(03)00488-1 - DOI - PubMed
- Flint HJ, Duncan SH, Scott KP, Louis P. Links between diet, gut microbiota composition and gut metabolism. Proc Nutr Soc 2015; 74:13-22; PMID:25268552; http://dx.doi.org/10.1017/S0029665114001463 - DOI - PubMed
Publication types
MeSH terms
Substances
Grants and funding
- BB/L004259/1/Biotechnology and Biological Sciences Research Council/United Kingdom
- BBH004815/1/Biotechnology and Biological Sciences Research Council/United Kingdom
- BB/H532091/1/Biotechnology and Biological Sciences Research Council/United Kingdom
LinkOut - more resources
Full Text Sources
Other Literature Sources