Fecal SCFAs and SCFA-producing Bacteria in Gut Microbiome of Human NAFLD As a Putative Link to Systemic T-cell Activation and Advanced Disease

Overview

Journal United European Gastroenterol J

Publisher Wiley

Specialty Gastroenterology

Date 2018 Dec 22

PMID 30574320

Citations 145

Authors

Monika Rau

Ateequr Rehman

Marcus Dittrich

Albert K Groen

Heike M Hermanns

Florian Seyfried

Niklas Beyersdorf

Thomas Dandekar

Philip Rosenstiel

Andreas Geier

Affiliations

Soon will be listed here.

Abstract

Background: Intestinal microbiota and their metabolites (e.g. short-chain fatty acids (SCFAs)) may influence nonalcoholic fatty liver disease (NAFLD).

Objective: The objective of this article is to analyze gut bacterial diversity together with fecal SCFA concentrations and immunophenotyping of peripheral blood in histology-proven NAFLD patients.

Methods: Thirty-two NAFLD patients (14 nonalcoholic fatty liver (NAFL), 18 nonalcoholic steatohepatitis (NASH)) and 27 healthy controls (HCs)) were included in this study. Bacterial communities in feces were profiled by 16S ribosomal RNA gene sequencing of the V3-V4 region. Fecal SCFA levels were analyzed by high-performance liquid chromatography. Fluorescence-activated cell sorting analysis was performed of peripheral blood mononuclear cells.

Results: NASH patients were characterized by higher abundance of Fusobacteria and Fusobacteriaceae compared to NAFL and HCs. Conforming to our finding that NAFLD patients had higher fecal acetate and propionate levels, taxonomical differences of fecal bacteria were dominated by SCFA-producing bacteria. Higher fecal propionate and acetate levels were associated with lower resting regulatory T-cells (rTregs) (CD4+CD45RA+CD25++) as well as higher Th17/rTreg ratio in peripheral blood as immunological characteristics of NASH patients.

Conclusions: NASH patients are characterized by a different gut microbiome composition with higher fecal SCFA levels and higher abundance of SCFA-producing bacteria in NAFLD. These changes are associated with immunological features of disease progression. Our data suggest an important role of the intestinal microbiome and immunomodulatory bacterial metabolites in human NAFLD.

Citing Articles

A critical review of microbiome-derived metabolic functions and translational research in liver diseases.

Ganesan R, Thirumurugan D, Vinayagam S, Kim D, Suk K, Iyer M Front Cell Infect Microbiol. 2025; 15:1488874.

PMID: 40066068 PMC: 11891185. DOI: 10.3389/fcimb.2025.1488874.

Gut microbiome and metabolome characteristics of patients with cholesterol gallstones suggest the preventive potential of prebiotics.

Liu Y, Li H, Sun T, Sun G, Jiang B, Liu M Imeta. 2025; 4(1):e70000.

PMID: 40027485 PMC: 11865347. DOI: 10.1002/imt2.70000.

The role of short-chain fatty acid in metabolic syndrome and its complications: focusing on immunity and inflammation.

Yu W, Sun S, Fu Q Front Immunol. 2025; 16:1519925.

PMID: 39991152 PMC: 11842938. DOI: 10.3389/fimmu.2025.1519925.

Gut microbiota and atrial cardiomyopathy.

Sun T, Song B, Li B Front Cardiovasc Med. 2025; 12:1541278.

PMID: 39968343 PMC: 11832500. DOI: 10.3389/fcvm.2025.1541278.

Bile acid activated receptors: Integrating immune and metabolic regulation in non-alcoholic fatty liver disease.

Biagioli M, Fiorucci S Liver Res. 2025; 5(3):119-141.

PMID: 39957845 PMC: 11791866. DOI: 10.1016/j.livres.2021.08.003.

References

Schloss P, Westcott S, Ryabin T, Hall J, Hartmann M, Hollister E . Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl Environ Microbiol. 2009; 75(23):7537-41. PMC: 2786419. DOI: 10.1128/AEM.01541-09. View

Yoneda M, Naka S, Nakano K, Wada K, Endo H, Mawatari H . Involvement of a periodontal pathogen, Porphyromonas gingivalis on the pathogenesis of non-alcoholic fatty liver disease. BMC Gastroenterol. 2012; 12:16. PMC: 3305584. DOI: 10.1186/1471-230X-12-16. View

Tsujimoto T, Kawaratani H, Kitazawa T, Uemura M, Fukui H . Innate immune reactivity of the ileum-liver axis in nonalcoholic steatohepatitis. Dig Dis Sci. 2012; 57(5):1144-51. DOI: 10.1007/s10620-012-2073-z. View

Bedossa P, Poitou C, Veyrie N, Bouillot J, Basdevant A, Paradis V . Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients. Hepatology. 2012; 56(5):1751-9. DOI: 10.1002/hep.25889. View

Vrieze A, van Nood E, Holleman F, Salojarvi J, Kootte R, Bartelsman J . Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012; 143(4):913-6.e7. DOI: 10.1053/j.gastro.2012.06.031. View

Zhu L, Baker S, Gill C, Liu W, Alkhouri R, Baker R . Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology. 2012; 57(2):601-9. DOI: 10.1002/hep.26093. View

Teixeira T, Grzeskowiak L, Franceschini S, Bressan J, Ferreira C, Peluzio M . Higher level of faecal SCFA in women correlates with metabolic syndrome risk factors. Br J Nutr. 2012; 109(5):914-9. DOI: 10.1017/S0007114512002723. View

Mouzaki M, Comelli E, Arendt B, Bonengel J, Fung S, Fischer S . Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology. 2013; 58(1):120-7. DOI: 10.1002/hep.26319. View

De Baere S, Eeckhaut V, Steppe M, De Maesschalck C, De Backer P, Van Immerseel F . Development of a HPLC-UV method for the quantitative determination of four short-chain fatty acids and lactic acid produced by intestinal bacteria during in vitro fermentation. J Pharm Biomed Anal. 2013; 80:107-15. DOI: 10.1016/j.jpba.2013.02.032. View

10.

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

11.

Smith P, Howitt M, Panikov N, Michaud M, Gallini C, Bohlooly-Y M . The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013; 341(6145):569-73. PMC: 3807819. DOI: 10.1126/science.1241165. View

12.

Russell W, Hoyles L, Flint H, Dumas M . Colonic bacterial metabolites and human health. Curr Opin Microbiol. 2013; 16(3):246-54. DOI: 10.1016/j.mib.2013.07.002. View

13.

Paulson J, Stine O, Corrada Bravo H, Pop M . Differential abundance analysis for microbial marker-gene surveys. Nat Methods. 2013; 10(12):1200-2. PMC: 4010126. DOI: 10.1038/nmeth.2658. View

14.

Fadrosh D, Ma B, Gajer P, Sengamalay N, Ott S, Brotman R . An improved dual-indexing approach for multiplexed 16S rRNA gene sequencing on the Illumina MiSeq platform. Microbiome. 2014; 2(1):6. PMC: 3940169. DOI: 10.1186/2049-2618-2-6. View

15.

Rahat-Rozenbloom S, Fernandes J, Gloor G, Wolever T . Evidence for greater production of colonic short-chain fatty acids in overweight than lean humans. Int J Obes (Lond). 2014; 38(12):1525-31. PMC: 3970979. DOI: 10.1038/ijo.2014.46. View

16.

Vital M, Howe A, Tiedje J . Revealing the bacterial butyrate synthesis pathways by analyzing (meta)genomic data. mBio. 2014; 5(2):e00889. PMC: 3994512. DOI: 10.1128/mBio.00889-14. View

17.

Arimatsu K, Yamada H, Miyazawa H, Minagawa T, Nakajima M, Ryder M . Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota. Sci Rep. 2014; 4:4828. PMC: 4010932. DOI: 10.1038/srep04828. View

18.

Park J, Kim M, Kang S, Jannasch A, Cooper B, Patterson J . Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway. Mucosal Immunol. 2014; 8(1):80-93. PMC: 4263689. DOI: 10.1038/mi.2014.44. View

19.

Blaut M . Gut microbiota and energy balance: role in obesity. Proc Nutr Soc. 2014; 74(3):227-34. DOI: 10.1017/S0029665114001700. View

20.

Provenzano J, Rocas I, Tavares L, Neves B, Siqueira Jr J . Short-chain Fatty Acids in Infected Root Canals of Teeth with Apical Periodontitis before and after Treatment. J Endod. 2015; 41(6):831-5. DOI: 10.1016/j.joen.2015.02.006. View