Gut Microbiota and Short Chain Fatty Acids: Implications in Glucose Homeostasis

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Feb 15

PMID 35163038

Authors

Piero Portincasa

Leonilde Bonfrate

Mirco Vacca

Maria De Angelis

Ilaria Farella

Elisa Lanza

Mohamad Khalil

David Q-H Wang

Markus Sperandio

Agostino Di Ciaula

Affiliations

Soon will be listed here.

Abstract

Gut microbiota encompasses a wide variety of commensal microorganisms consisting of trillions of bacteria, fungi, and viruses. This microbial population coexists in symbiosis with the host, and related metabolites have profound effects on human health. In this respect, gut microbiota plays a pivotal role in the regulation of metabolic, endocrine, and immune functions. Bacterial metabolites include the short chain fatty acids (SCFAs) acetate (C2), propionate (C3), and butyrate (C4), which are the most abundant SCFAs in the human body and the most abundant anions in the colon. SCFAs are made from fermentation of dietary fiber and resistant starch in the gut. They modulate several metabolic pathways and are involved in obesity, insulin resistance, and type 2 diabetes. Thus, diet might influence gut microbiota composition and activity, SCFAs production, and metabolic effects. In this narrative review, we discuss the relevant research focusing on the relationship between gut microbiota, SCFAs, and glucose metabolism.

Citing Articles

Gut over Mind: Exploring the Powerful Gut-Brain Axis.

Petrut S, Bragaru A, Munteanu A, Moldovan A, Moldovan C, Rusu E Nutrients. 2025; 17(5).

PMID: 40077713 PMC: 11901622. DOI: 10.3390/nu17050842.

Unveiling roles of beneficial gut bacteria and optimal diets for health.

Kumar S, Mukherjee R, Gaur P, Leal E, Lyu X, Ahmad S Front Microbiol. 2025; 16:1527755.

PMID: 40041870 PMC: 11877911. DOI: 10.3389/fmicb.2025.1527755.

The Results of Intestinal Villi of Laying Hens Exposed With Avian Pathogenic (APEC) After Giving Citric Acid and Dextrose.

Warsito S, Lamid M, Al-Arif M, Hermadi H, Sabdoningrum E, Ayuti S Vet Med Int. 2025; 2025:6623764.

PMID: 40041134 PMC: 11876522. DOI: 10.1155/vmi/6623764.

From Dysbiosis to Hepatic Inflammation: A Narrative Review on the Diet-Microbiota-Liver Axis in Steatotic Liver Disease.

Pasta A, Formisano E, Calabrese F, Marabotto E, Furnari M, Bodini G Microorganisms. 2025; 13(2).

PMID: 40005608 PMC: 11857840. DOI: 10.3390/microorganisms13020241.

Advances in Metabolic Bariatric Surgeries and Endoscopic Therapies: A Comprehensive Narrative Review of Diabetes Remission Outcomes.

Ghusn W, Zeineddine J, Betancourt R, Gajjar A, Yang W, Robertson A Medicina (Kaunas). 2025; 61(2).

PMID: 40005466 PMC: 11857516. DOI: 10.3390/medicina61020350.

References

Baothman O, Zamzami M, Taher I, Abubaker J, Abu-Farha M . The role of Gut Microbiota in the development of obesity and Diabetes. Lipids Health Dis. 2016; 15:108. PMC: 4912704. DOI: 10.1186/s12944-016-0278-4. View

Mohammad S, Thiemermann C . Role of Metabolic Endotoxemia in Systemic Inflammation and Potential Interventions. Front Immunol. 2021; 11:594150. PMC: 7829348. DOI: 10.3389/fimmu.2020.594150. View

Derrien M, van Baarlen P, Hooiveld G, Norin E, Muller M, de Vos W . Modulation of Mucosal Immune Response, Tolerance, and Proliferation in Mice Colonized by the Mucin-Degrader Akkermansia muciniphila. Front Microbiol. 2011; 2:166. PMC: 3153965. DOI: 10.3389/fmicb.2011.00166. View

Kreznar J, Keller M, Traeger L, Rabaglia M, Schueler K, Stapleton D . Host Genotype and Gut Microbiome Modulate Insulin Secretion and Diet-Induced Metabolic Phenotypes. Cell Rep. 2017; 18(7):1739-1750. PMC: 5325228. DOI: 10.1016/j.celrep.2017.01.062. View

Kim M, Kang S, Park J, Yanagisawa M, Kim C . Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice. Gastroenterology. 2013; 145(2):396-406.e1-10. DOI: 10.1053/j.gastro.2013.04.056. View

Martinez-Guryn K, Hubert N, Frazier K, Urlass S, Musch M, Ojeda P . Small Intestine Microbiota Regulate Host Digestive and Absorptive Adaptive Responses to Dietary Lipids. Cell Host Microbe. 2018; 23(4):458-469.e5. PMC: 5912695. DOI: 10.1016/j.chom.2018.03.011. View

Chambers E, Preston T, Frost G, Morrison D . Role of Gut Microbiota-Generated Short-Chain Fatty Acids in Metabolic and Cardiovascular Health. Curr Nutr Rep. 2018; 7(4):198-206. PMC: 6244749. DOI: 10.1007/s13668-018-0248-8. View

Hamaker B, Tuncil Y . A perspective on the complexity of dietary fiber structures and their potential effect on the gut microbiota. J Mol Biol. 2014; 426(23):3838-50. DOI: 10.1016/j.jmb.2014.07.028. View

Kelly C, Zheng L, Campbell E, Saeedi B, Scholz C, Bayless A . Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function. Cell Host Microbe. 2015; 17(5):662-71. PMC: 4433427. DOI: 10.1016/j.chom.2015.03.005. View

10.

Schonfeld P, Wojtczak L . Short- and medium-chain fatty acids in energy metabolism: the cellular perspective. J Lipid Res. 2016; 57(6):943-54. PMC: 4878196. DOI: 10.1194/jlr.R067629. View

11.

Gutierrez-Diaz I, Fernandez-Navarro T, Sanchez B, Margolles A, Gonzalez S . Mediterranean diet and faecal microbiota: a transversal study. Food Funct. 2016; 7(5):2347-56. DOI: 10.1039/c6fo00105j. View

12.

Mollica M, Raso G, Cavaliere G, Trinchese G, De Filippo C, Aceto S . Butyrate Regulates Liver Mitochondrial Function, Efficiency, and Dynamics in Insulin-Resistant Obese Mice. Diabetes. 2017; 66(5):1405-1418. DOI: 10.2337/db16-0924. View

13.

Mancabelli L, Milani C, Lugli G, Fontana F, Turroni F, Van Sinderen D . The Impact of Primer Design on Amplicon-Based Metagenomic Profiling Accuracy: Detailed Insights into Bifidobacterial Community Structure. Microorganisms. 2020; 8(1). PMC: 7023036. DOI: 10.3390/microorganisms8010131. View

14.

Chambers E, Viardot A, Psichas A, Morrison D, Murphy K, Zac-Varghese S . Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut. 2014; 64(11):1744-54. PMC: 4680171. DOI: 10.1136/gutjnl-2014-307913. View

15.

Vitale M, Giacco R, Laiola M, Della Pepa G, Luongo D, Mangione A . Acute and chronic improvement in postprandial glucose metabolism by a diet resembling the traditional Mediterranean dietary pattern: Can SCFAs play a role?. Clin Nutr. 2020; 40(2):428-437. DOI: 10.1016/j.clnu.2020.05.025. View

16.

Freeland K, Wolever T . Acute effects of intravenous and rectal acetate on glucagon-like peptide-1, peptide YY, ghrelin, adiponectin and tumour necrosis factor-alpha. Br J Nutr. 2009; 103(3):460-6. DOI: 10.1017/S0007114509991863. View

17.

Saeedi B, Kao D, Kitzenberg D, Dobrinskikh E, Schwisow K, Masterson J . HIF-dependent regulation of claudin-1 is central to intestinal epithelial tight junction integrity. Mol Biol Cell. 2015; 26(12):2252-62. PMC: 4462943. DOI: 10.1091/mbc.E14-07-1194. View

18.

Federici M . Gut microbiome and microbial metabolites: a new system affecting metabolic disorders. J Endocrinol Invest. 2019; 42(9):1011-1018. DOI: 10.1007/s40618-019-01022-9. View

19.

Hald S, Schioldan A, Moore M, Dige A, Laerke H, Agnholt J . Effects of Arabinoxylan and Resistant Starch on Intestinal Microbiota and Short-Chain Fatty Acids in Subjects with Metabolic Syndrome: A Randomised Crossover Study. PLoS One. 2016; 11(7):e0159223. PMC: 4951149. DOI: 10.1371/journal.pone.0159223. View

20.

LeBlanc J, Chain F, Martin R, Bermudez-Humaran L, Courau S, Langella P . Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria. Microb Cell Fact. 2017; 16(1):79. PMC: 5423028. DOI: 10.1186/s12934-017-0691-z. View