Abstract
Obesity has been a worldwide multifactorial epidemic malady for the last 2 decades. Changes in gut microbiota composition and its metabolites — short-chain fatty acids (SCFAs) — have been associated with obesity. Recent evidence suggests that SCFAs made by the gut microbiota may regulate directly or indirectly physiological and pathological processes in relation to obesity. We review the influence of gut microbiota in energy, glucose, and lipid homeostasis control via their metabolites. Gut microbial disturbances in obese children may have a role in their metabolism. At first glance, excessive short-chain fatty acids produced by a particular gut microbiota represent an additional energy source, and should cause an imbalance in energy regulation, contributing to obesity. However, simultaneously, SCFA participates in glucose-stimulated insulin secretion from the pancreatic β-cells through interaction with the FFA2 and FFA3 receptors, and release of peptide hormones which control appetite. This apparent contradictory situation may indicate the involvement of additional particular bacteria or bacterial components or metabolites that may trigger regulatory cascades by interaction with some G-protein-coupled membrane receptors.
This is a preview of subscription content, access via your institution.
References
- 1.
OECD (2014) Obesity Update 2014. http://www.oecd.org/health/obesity-update.htm
- 2.
WHO (2012) Population-based approaches to childhood obesity prevention. Geneva, World Health Organization, 2012. Available at: http://apps.who.int/iris/bitstream/10665/80149/1/9789241504782_eng.pdf?ua=1. Accessed March 2017
- 3.
Hartstra AV, Bouter KE, Bäckhed F, Nieuwdorp M (2015) Insights into the role of the microbiome in obesity and type 2 diabetes. Diabetes Care 38:159–165
- 4.
Aceves-Martins M, Llauradó E, Tarro L et al (2016) Obesity-promoting factors in Mexican children and adolescents: challenges and opportunities. Glob Health Action 9:29625
- 5.
Murugesan S, Nirmalkar K, García-Espitia M et al (2017) Current insight into the role of gut microbiota in Mexican childhood obesity. SOJ Pharm Pharm Sci 4:1–5
- 6.
Wild SH, Byrne CD (2006) Risk factors for diabetes and coronary heart disease Dyslipidaemia. BMJ 333:1009–1010
- 7.
Freedman DS, Zuguo M, Srinivasan SR et al (2007) Cardiovascular risk factors and excess adiposity among overweight children and adolescents: the Bogalusa heart study. J Pediatr 150(1):12–17
- 8.
Bruzzese E, Volpicelli M, Squaglia M et al (2006) Impact of prebiotics on human health. Dig Liver Dis 38(Suppl 2):S283–S287
- 9.
Rodriguez JM, Murphy K, Stanton C et al (2015) The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis 26:26050
- 10.
Marchesi JR, Adams DH, Fava F et al (2016) The gut microbiota and host health: a new clinical frontier. Gut 65(2):330–339
- 11.
Jandhyala SM, Talukdar R, Subramanyam C et al (2015) Role of the normal gut microbiota. World J Gastroenterol 21(29):8787–8803
- 12.
Macfarlane GT, Macfarlane S (2012) Bacteria, colonic fermentation, and gastrointestinal health. J AOAC Int 95:50–60
- 13.
Cummings JH, Pomare EW, Branch WJ et al (1987) short-chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 28:1221–1227
- 14.
Ríos-Covián D, Ruas-Madiedo P, Margolles A et al (2016) Intestinal short-chain fatty acids and their link with diet and human health. Front Microbiol 7:185
- 15.
Wall R, Ross RP, Shanahan F et al (2009) Metabolic activity of the enteric microbiota influences the fatty acid composition of murine and porcine liver and adipose tissues. Am J Clin Nutr 89:1393–1401
- 16.
Russell SL, Gold MJ, Hartmann M et al (2012) Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma. EMBO Rep 13:440–447
- 17.
Smith EA, Macfarlane GT (1997) Dissimilatory amino acid metabolism in human colonic bacteria. Anaerobe 3:327–337
- 18.
Sanchez JI, Marzorati M, Grootaert C et al (2009) Arabinoxylan-oligosaccharides (AXOS) affect the protein/carbohydrate fermentation balance and microbial population dynamics of the simulator of human intestinal microbial ecosystem. Microb Biotechnol 2:101–113
- 19.
Louis P, Young P, Holtrop G et al (2010) Diversity of human colonic butyrate-producing bacteria revealed by analysis of the butyryl-CoA:acetate CoA-transferase gene. Environ Microbiol 12:304–314
- 20.
Rey FE, Faith JJ, Bain J et al (2010) Dissecting the in vivo metabolic potential of two human gut acetogens. J Biol Chem 285:22082–22090
- 21.
Scott KP, Martin JC, Campbell G et al (2006) Whole-genome transcription profiling reveals genes up-regulated by growth on fucose in the human gut bacterium “Roseburia inulinivorans”. J Bacteriol 188:4340–4349
- 22.
Duncan SH, Barcenilla A, Stewart CS et al (2002) Acetate utilization and butyryl coenzyme a (CoA): acetate-CoA transferase in butyrate-producing bacteria from the human large intestine. Appl Environ Microbiol 68:5186–5190
- 23.
Dagher PC, Egnor RW, Taglietta-Kohlbrecteri A et al (1996) Short-chain fatty acids inhibit cAMP-mediated chloride secretion in rat colon. Am J Phys 271:C1853–C1860
- 24.
Hamer HM, Jonkers D, Venema K et al (2008) Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther 27(2):104–119
- 25.
Krautkramer KA, Kreznar JH, Romano KA et al (2016) Diet–microbiota interactions mediate global epigenetic programming in multiple host tissues. Mol Cell 64(5):982–992
- 26.
Al-Lahham SH, Peppelenbosch MP, Roelofsen H et al (2010) Biological effects of propionic acid in humans; metabolism, potential applications and underlying mechanisms. Biochim Biophys Acta 1:1175–1183
- 27.
Vogt JA, Wolever TMS (2003) Fecal acetate is inversely related to acetate absorption from the human rectum and distal colon. J Nutr 133:3145–3148
- 28.
Frost G, Sleeth ML, Sahuri-Arisoylu M et al (2014) The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat Commun 5:3611
- 29.
Kotzampassi K, Giamarellos-Bourboulis EJ, Stavrou G (2014) Obesity as a consequence of gut bacteria and diet interactions. ISRN Obes 2014:651895
- 30.
Hong YH, Nishimura Y, Hishikawa D et al (2005) Acetate and propionate short-chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology 146(12):5092–5099
- 31.
Scheppach W (1994) Effects of short-chain fatty acids on gut morphology and function. Gut 35(1 Suppl):S35–S38
- 32.
den Besten G, van Eunen K, Groen AK et al (2013) The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 54:2325–2340
- 33.
Palmer C, Bik EM, DiGiulio DB et al (2007) Development of the human infant intestinal microbiota. PLoS Biol 5(7):e177
- 34.
Backhed F, Ley RE, Sonnenburg JL et al (2005) Host–bacterial mutualism in the human intestine. Science 307(5717):1915–1920
- 35.
Devaraj S, Hemarajata P, Versalovic J (2013) The human gut microbiome and body metabolism: implications for obesity and diabetes. Clin Chem 59(4):617–628
- 36.
Ursell LK, Metcalf JL, Parfrey LW et al (2012) Defining the human microbiome. Nutr Rev 70(Suppl 1):S38–S44
- 37.
Ley RE (2010) Obesity and the human microbiome. Curr Opin Gastroenterol 26(1):5–11
- 38.
Bäckhed F, Ding H, Wang T et al (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA 101(44):15718–15723
- 39.
DiBaise JK, Zhang H, Crowell MD et al (2008) Gut microbiota and its possible relationship with obesity. Mayo Clin Proc 83(4):460–469
- 40.
Flint HJ (2011) Obesity and the gut microbiota. J Clin Gastroenterol 45(Suppl):S128–S132
- 41.
Ley R, Turnbaugh P, Klein S et al (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444:1022–1023
- 42.
Schwiertz A, Taras D, Schäfer K et al (2010) Microbiota and SCFA in lean and overweight healthy subjects. Obesity 18:190–195
- 43.
Kalliomäki M, Collado MC, Salminen S et al (2008) Early differences in fecal microbiota composition in children may predict overweight. Am J Clin Nutr 87:534–538
- 44.
Bervoets L, Van Hoorenbeeck K, Kortleven I et al (2013) Differences in gut microbiota composition between obese and lean children: a cross-sectional study. Gut Pathogens 5:10. https://doi.org/10.1186/1757-4749-5-10
- 45.
Murugesan S, Ulloa-Martínez M, Martínez-Rojano H et al (2015) Study of the diversity and short-chain fatty acids production by the bacterial community in overweight and obese Mexican children. Eur J Clin Microbiol Infect Dis 34:1337–1346
- 46.
Nirmalkar K, Murugesan S, Pizano-Zárate ML et al (2016) Endothelial dysfunction in Mexican obese children, is there a role of the gut microbiota? Obes Control Ther 3(1):1–4
- 47.
Masotti A (2012) Interplays between gut microbiota and gene expression regulation by miRNAs. Front Cell Infect Microbiol 2:137. https://doi.org/10.3389/fcimb.2012.00137 eCollection 2012
- 48.
Medzhitov R (2007) Recognition of microorganisms and activation of the immune response. Nature 449(7164):819–826
- 49.
Marques FZ, Mackay CR, Kaye DM (2017) Beyond gut feelings: how the gut microbiota regulates blood pressure. Nat Rev Cardiol Aug 24 [Epub before print]. https://doi.org/10.1038/nrcardio.2017.120
- 50.
Clark T (2017) G-protein coupled receptors: answers from simulations. Beilstein J Org Chem 13:1071–1078. https://doi.org/10.3762/bjoc.13.106 eCollection 2017
- 51.
Leurs R, Bakker RA, Timmerman H, de Esch IJ (2005) The histamine H3 receptor: from gene cloning to H3 receptor drugs. Nat Rev Drug Discov 4(2):107–120
- 52.
Hansen AH, Sergeev E, Pandey SK et al (2017) development and characterization of a fluorescent tracer for the free fatty acid receptor 2 (FFA2/GPR43). J Med Chem 60(13):5638–5645
- 53.
Won YJ, Lu VB, Puhl HL, Ikeda SR (2013) β-Hydroxybutyrate modulates N-type calcium channels in rat sympathetic neurons by acting as an agonist for the G-protein-coupled receptor FFA3. J Neurosci 33(49):19314–19325
- 54.
Muredda L, Kępczyńska MA, Zaibi MS et al (2017) IL-1β and TNFα inhibit GPR120 (FFAR4) and stimulate GPR84 (EX33) and GPR41 (FFAR3) fatty acid receptor expression in human adipocytes: implications for the anti-inflammatory action of n-3 fatty acids. Arch Physiol Biochem 24:1–12
- 55.
Tang C, Offermanns S (2017) FFA2 and FFA3 in metabolic regulation. Handb Exp Pharmacol 236:205–220
- 56.
Priyadarshini M, Wicksteed B, Schiltz GE et al (2016) SCFA receptors in pancreatic β cells: novel diabetes targets? Trends Endocrinol Metab 27(9):653–664
- 57.
Chambers ES, Morrison DJ, Frost G (2015) Control of appetite and energy intake by SCFA: what are the potential underlying mechanisms? Proc Nutr Soc 74(3):328–336
- 58.
Kaji I, Akiba Y, Furuyama T et al (2017) Free fatty acid receptor 3 activation suppresses neurogenic motility in rat proximal colon. Neurogastroenterol Motil. https://doi.org/10.1111/nmo.13157
- 59.
Cani PD (2017) Gut cell metabolism shapes the microbiome. Science 357(6351):548–549
- 60.
Goffredo M, Mass K, Parks EJ et al (2016) Role of gut microbiota and short-chain fatty acids in modulating energy harvest and fat partitioning in youth. J Clin Endocrinol Metab 101(11):4367–4376
Funding
Cinvestav-IPN, Fundación Miguel Alemán A. C., CONACyT 163235 INFR-2011-01, and FONSEC SS/IMSS/ISSSTE-CONACYT-233361 grants to JGM supported this work. We thank a Postdoctoral Fellowship from FONSEC SS/IMSS/ISSSTE-CONACYT-233361 to SM, a M. Sc. Fellowship CONACyT394921 to DRS.
Author information
Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Ethical approval
Not applicable.
Informed consent
Not applicable.
Rights and permissions
About this article
Cite this article
Murugesan, S., Nirmalkar, K., Hoyo-Vadillo, C. et al. Gut microbiome production of short-chain fatty acids and obesity in children. Eur J Clin Microbiol Infect Dis 37, 621–625 (2018). https://doi.org/10.1007/s10096-017-3143-0
Received:
Accepted:
Published:
Issue Date:
Keywords
- Short-chain Fatty Acids (SCFAs)
- FFA1 Receptor
- Glucose-stimulated Insulin Secretion
- SCFA Production
- Butyric Acid-producing Bacteria