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Review article: short chain fatty acids as potential therapeutic agents in human gastrointestinal and inflammatory disorders

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Gill, P. A., van Zelm, M. C., Muir, J. G., Gibson, P. R.·2018·Alimentary Pharmacology & Therapeutics
DOI 10.1111/apt.14689
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Abstract

Summary: Background: Butyrate, propionate and acetate are short chain fatty acids ( SCFA ), important for maintaining a healthy colon and are considered as protective in colorectal carcinogenesis. However, they may also regulate immune responses and the composition of the intestinal microbiota. Consequently, their importance in a variety of chronic inflammatory diseases is emerging. Aims: To review the physiology and metabolism of SCFA in humans, cellular and molecular mechanisms by which SCFA may act in health and disease, and approaches for therapeutic delivery of SCFA . Methods: A PubMed literature search was conducted for clinical and pre‐clinical studies using search terms: ‘dietary fibre’, short‐chain fatty acids’, ‘acetate’, ‘propionate’, ‘butyrate’, ‘inflammation’, ‘immune’, ‘gastrointestinal’, ‘metabolism’. Results: A wide range of pre‐clinical evidence supports roles for SCFA as modulators of not only colonic function, but also multiple inflammatory and metabolic processes. SCFA are implicated in many autoimmune, allergic and metabolic diseases. However, translating effects of SCFA from animal studies to human disease is limited by physiological and dietary differences and by the challenge of delivering sufficient amounts of SCFA to the target sites that include the colon and the systemic circulation. Development of novel targeted approaches for colonic delivery, combined with postbiotic supplementation, may represent desirable strategies to achieve adequate targeted SCFA delivery. Conclusions: There is a large array of potential disease‐modulating effects of SCFA . Adequate targeted delivery to the sites of action is the main limitation of such application. The ongoing development and evaluation of novel delivery techniques offer potential for translating promise to therapeutic benefit.

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  • SCFAs have been implicated in GI function, blood-pressure regulation, circadian rhythm, and (neuro)immune function.

    “SCFAs have been implicated in a variety of host processes including GI function (Gill et al., 2018), blood-pressure regulation (Pluznick, 2017), circadian rhythm (Tahara et al., 2018), and (neuro)immune function (Erny et al., 2017)”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Gill et al., 2018

  • Minor amounts of SCFAs can be attained by the consumption of fermented foods.

    “Finally, minor amounts of SCFAs can be attained by the consumption of fermented foods (Gill et al., 2018).”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Gill et al., 2018

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  1. Threapleton DE, Greenwood DC, Evans CE, et al. Dietary fibre intake and risk of cardiovascular disease: systematic review and meta-analysis. BMJ. 2013;347:f6879.
  2. Bingham SA, Day NE, Luben R, et al. Dietary fibre in food and pro- tection against colorectal cancer in the European Prospective Inves- tigation into Cancer and Nutrition (EPIC): an observational study. Lancet. 2003;361:1496-1501.
  3. Montonen J, Knekt P, Jarvinen R, Aromaa A, Reunanen A. Whole- grain and fiber intake and the incidence of type 2 diabetes. Am J Clin Nutr. 2003;77:622-629.
  4. Pouteau E, Nguyen P, Ballevre O, Krempf M. Production rates and metabolism of short-chain fatty acids in the colon and whole body using stable isotopes. Proc Nutr Soc. 2003;62:87-93.
  5. Siler SQ, Neese RA, Hellerstein MK. De novo lipogenesis, lipid kinetics, and whole-body lipid balances in humans after acute alco- hol consumption. Am J Clin Nutr. 1999;70:928-936.
  6. Hoverstad T, Midtvedt T. Short-chain fatty acids in germfree mice and rats. J Nutr. 1986;116:1772-1776.
  7. Yao CK, Muir JG, Gibson PR. Review article: insights into colonic protein fermentation, its modulation and potential health implica- tions. Aliment Pharmacol Ther. 2016;43:181-196.
  8. Cummings JH, Macfarlane GT. The control and consequences of bacterial fermentation in the human colon. J Appl Bacteriol. 1991;70:443-459.
  9. Stephen AM, Champ MM, Cloran SJ, et al. Dietary fibre in Europe: current state of knowledge on definitions, sources, recommendations, intakes and relationships to health. Nutr Res Rev. 2017;30:149-190.
  10. Eswaran S, Muir J, Chey WD. Fiber and functional gastrointestinal disorders. Am J Gastroenterol. 2013;108:718-727.
  11. Roberts CL, Keita AV, Duncan SH, et al. Translocation of Crohn's disease Escherichia coli across M-cells: contrasting effects of soluble plant fibres and emulsifiers. Gut. 2010;59:1331-1339.
  12. Stephen AM, Cummings JH. Mechanism of action of dietary fibre in the human colon. Nature. 1980;284:283-284.
  13. Cummings JH. Constipation, dietary fibre and the control of large bowel function. Postgrad Med J. 1984;60:811-819.
  14. McIntyre A, Gibson PR, Young GP. Butyrate production from diet- ary fibre and protection against large bowel cancer in a rat model. Gut. 1993;34:386-391.
  15. Christl SU, Murgatroyd PR, Gibson GR, Cummings JH. Production, metabolism, and excretion of hydrogen in the large intestine. Gas- troenterology. 1992;102:1269-1277.
  16. Stewart ML, Timm DA, Slavin JL. Fructooligosaccharides exhibit more rapid fermentation than long-chain inulin in an in vitro fer- mentation system. Nutr Res. 2008;28:329-334.
  17. Kaur A, Rose DJ, Rumpagaporn P, Patterson JA, Hamaker BR. In vitro batch fecal fermentation comparison of gas and short-chain fatty acid production using "slowly fermentable" dietary fibers. J Food Sci. 2011;76:H137-H142.
  18. Walker AW, Ince J, Duncan SH, et al. Dominant and diet-respon- sive groups of bacteria within the human colonic microbiota. ISME J. 2011;5:220-230.
  19. Ze X, Duncan SH, Louis P, Flint HJ. Ruminococcus bromii is a key- stone species for the degradation of resistant starch in the human colon. ISME J. 2012;6:1535-1543.
  20. Kovatcheva-Datchary P, Egert M, Maathuis A, et al. Linking phylo- genetic identities of bacteria to starch fermentation in an in vitro model of the large intestine by RNA-based stable isotope probing. Environ Microbiol. 2009;11:914-926.
  21. Flint HJ, Duncan SH, Scott KP, Louis P. Links between diet, gut microbiota composition and gut metabolism. Proc Nutr Soc. 2015;74:13-22.
  22. Gibson GR, Macfarlane GT, Cummings JH. Sulphate reducing bacte- ria and hydrogen metabolism in the human large intestine. Gut. 1993;34:437-439.
  23. Macfarlane S, Macfarlane GT. Regulation of short-chain fatty acid production. Proc Nutr Soc. 2003;62:67-72.
  24. James SL, Christophersen CT, Bird AR, et al. Abnormal fibre usage in UC in remission. Gut. 2015;64:562-570.
  25. Perman JA, Modler S, Olson AC. Role of pH in production of hydrogen from carbohydrates by colonic bacterial flora. Studies in vivo and in vitro. J Clin Invest. 1981;67:643-650.
  26. Henningsson AM, Bjorck IM, Nyman EM. Combinations of indi- gestible carbohydrates affect short-chain fatty acid formation in the hindgut of rats. J Nutr. 2002;132:3098-3104.
  27. Phillips J, Muir JG, Birkett A, et al. Effect of resistant starch on fecal bulk and fermentation-dependent events in humans. Am J Clin Nutr. 1995;62:121-130.
  28. den Besten G, Lange K, Havinga R, et al. Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids. Am J Physiol Gastrointest Liver Physiol. 2013;305:G900-G910.
  29. Mariat D, Firmesse O, Levenez F, et al. The Firmicutes/Bacteroide- tes ratio of the human microbiota changes with age. BMC Microbiol. 2009;9:123.
  30. Woodmansey EJ, McMurdo ME, Macfarlane GT, Macfarlane S. Comparison of compositions and metabolic activities of fecal micro- biotas in young adults and in antibiotic-treated and non-antibiotic- treated elderly subjects. Appl Environ Microbiol. 2004;70:6113- 6122.
  31. Cummings JH, Pomare EW, Branch WJ, Naylor CP, Macfarlane GT. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut. 1987;28:1221-1227.
  32. Koziolek M, Grimm M, Becker D, et al. Investigation of pH and temperature profiles in the gi tract of fasted human subjects using the intellicap((R)) system. J Pharm Sci. 2015;104:2855-2863.
  33. Muir JG, Yeow EG, Keogh J, et al. Combining wheat bran with resistant starch has more beneficial effects on fecal indexes than does wheat bran alone. Am J Clin Nutr. 2004;79:1020-1028.
  34. Timm D, Willis H, Thomas W, Sanders L, Boileau T, Slavin J. The use of a wireless motility device (SmartPill(R)) for the measurement of gastrointestinal transit time after a dietary fibre intervention. Br J Nutr. 2011;105:1337-1342.
  35. Jin X, Li X, Zhao N, Angelidaki I, Zhang Y. Bio-electrolytic sensor for rapid monitoring of volatile fatty acids in anaerobic digestion process. Water Res. 2016;111:74-80.
  36. Govers MJ, Gannon NJ, Dunshea FR, Gibson PR, Muir JG. Wheat bran affects the site of fermentation of resistant starch and luminal indexes related to colon cancer risk: a study in pigs. Gut. 1999;45:840-847.
  37. McIntyre A, Young GP, Taranto T, Gibson PR, Ward PB. Different fibers have different regional effects on luminal contents of rat colon. Gastroenterology. 1991;101:1274-1281.
  38. Lewis SJ, Heaton KW. Increasing butyrate concentration in the distal colon by accelerating intestinal transit. Gut. 1997;41:245-251.
  39. El Oufir L, Flourie B, Bruley des Varannes, S, et al. Relations between transit time, fermentation products, and hydrogen con- suming flora in healthy humans. Gut. 1996;38:870-877.
  40. Cherbut C, Ferrier L, Roze C, et al. Short-chain fatty acids modify colonic motility through nerves and polypeptide YY release in the rat. Am J Physiol. 1998;275:G1415-G1422.
  41. Psichas A, Sleeth ML, Murphy KG, et al. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int J Obes. 2015;39:424-429.
  42. Chambers ES, Viardot A, Psichas A, et al. Effects of targeted deliv- ery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut. 2015;64:1744-1754.
  43. Canfora EE, van der Beek CM, Jocken JWE, et al. Colonic infusions of short-chain fatty acid mixtures promote energy metabolism in overweight/obese men: a randomized crossover trial. Sci Rep. 2017;7:2360.
  44. Savage AP, Adrian TE, Carolan G, Chatterjee VK, Bloom SR. Effects of peptide YY (PYY) on mouth to caecum intestinal transit time and on the rate of gastric emptying in healthy volunteers. Gut. 1987;28:166-170.
  45. Knowles SE, Jarrett IG, Filsell OH, Ballard FJ. Production and uti- lization of acetate in mammals. Biochem J. 1974;142:401-411.
  46. Sarkola T, Iles MR, Kohlenberg-Mueller K, Eriksson CJ. Ethanol, acetaldehyde, acetate, and lactate levels after alcohol intake in white men and women: effect of 4-methylpyrazole. Alcohol Clin Exp Res. 2002;26:239-245.
  47. Walter JH, Thompson GN, Leonard JV, Heatherington CS, Bartlett K. Measurement of propionate turnover in vivo using sodium [2H5] propionate and sodium [13C]propionate. Clin Chim Acta. 1989;182:141-150.
  48. Scheppach W, Pomare EW, Elia M, Cummings JH. The contribution of the large intestine to blood acetate in man. Clin Sci. 1991;80:177-182.
  49. Wolever TM, Josse RG, Leiter LA, Chiasson JL. Time of day and glucose tolerance status affect serum short-chain fatty acid concen- trations in humans. Metabolism. 1997;46:805-811.
  50. Todesco T, Zamboni M, Armellini F, et al. Plasma acetate levels in a group of obese diabetic, obese normoglycemic, and control subjects and their relationships with other blood parameters. Am J Gastroen- terol. 1993;88:751-755.
  51. Mannion DT, Furey A, Kilcawley KN. Comparison and validation of 2 analytical methods for the determination of free fatty acids in dairy products by gas chromatography with flame ionization detec- tion. J Dairy Sci. 2016;99:5047-5063.
  52. Malbasa RV, Loncar ES, Vitas JS, Canadanovic-Brunet JM. Influence of starter cultures on the antioxidant activity of kombucha bever- age. Food Chem. 2011;127:1727-1731.
  53. Sokollek SJ, Hertel C, Hammes WP. Cultivation and preservation of vinegar bacteria. J Biotechnol. 1998;60:195-206.
  54. Cantor MD, van den Tempel T, Hansen TK, Ard€ o Y. Blue cheese. Cheese: Chemistry, Physics and Microbiology 2004;2:175-198.
  55. Bolduc MP, Raymond Y, Fustier P, Champagne CP, Vuillemard JC. Sensitivity of bifidobacteria to oxygen and redox potential in non- fermented pasteurized milk. Int Dairy J. 2006;16:1038-1048.
  56. Shah NP, Lankaputhra WEV, Britz ML, Kyle WSA. Survival of Lacto- bacillus-Acidophilus and Bifidobacterium-Bifidum in commercial yogurt during refrigerated storage. Int Dairy J. 1995;5:515-521.
  57. Fox PF, Wallace JM, Morgan S, Lynch CM, Niland EJ, Tobin J. Acceleration of cheese ripening. Anton Leeuw Int J Microbiol. 1996;70:271-297.
  58. Oliveira RPD, Perego P, de Oliveira MN, Converti A. Growth, organic acids profile and sugar metabolism of Bifidobacterium lactis in co-culture with Streptococcus thermophilus: the inulin effect. Food Res Int. 2012;48:21-27.
  59. Fleming SE, Choi SY, Fitch MD. Absorption of short-chain fatty acids from the rat cecum in vivo. J Nutr. 1991;121:1787-1797.
  60. Stein J, Zores M, Schroder O. Short-chain fatty acid (SCFA) uptake into Caco-2 cells by a pH-dependent and carrier mediated transport mechanism. Eur J Nutr. 2000;39:121-125.
  61. Mascolo N, Rajendran VM, Binder HJ. Mechanism of short-chain fatty acid uptake by apical membrane vesicles of rat distal colon. Gastroenterology. 1991;101:331-338.
  62. Miyauchi S, Gopal E, Fei YJ, Ganapathy V. Functional identification of SLC5A8, a tumor suppressor down-regulated in colon cancer, as a Na(+)-coupled transporter for short-chain fatty acids. J Biol Chem. 2004;279:13293-13296.
  63. Borthakur A, Priyamvada S, Kumar A, et al. A novel nutrient sensing mechanism underlies substrate-induced regulation of monocarboxy- late transporter-1. Am J Physiol Gastrointest Liver Physiol. 2012;303: G1126-G1133.
  64. Goncalves P, Catarino T, Gregorio I, Martel F. Inhibition of butyrate uptake by the primary bile salt chenodeoxycholic acid in intestinal epithelial cells. J Cell Biochem. 2012;113:2937-2947.
  65. Kumar A, Alrefai WA, Borthakur A, Dudeja PK. Lactobacillus aci- dophilus counteracts enteropathogenic E. coli-induced inhibition of butyrate uptake in intestinal epithelial cells. Am J Physiol Gastroin- test Liver Physiol. 2015;309:G602-G607.
  66. Peters SG, Pomare EW, Fisher CA. Portal and peripheral blood short chain fatty acid concentrations after caecal lactulose instilla- tion at surgery. Gut. 1992;33:1249-1252.
  67. Boets E, Gomand SV, Deroover L, et al. Systemic availability and metabolism of colonic-derived short-chain fatty acids in healthy subjects: a stable isotope study. J Physiol. 2017;595: 541-555.
  68. Muir JG, Lu ZX, Young GP, Cameron-Smith D, Collier GR, O'Dea K. Resistant starch in the diet increases breath hydrogen and serum acetate in human subjects. Am J Clin Nutr. 1995;61:792-799.
  69. Lecerf JM, Depeint F, Clerc E, et al. Xylo-oligosaccharide (XOS) in combination with inulin modulates both the intestinal environment and immune status in healthy subjects, while XOS alone only shows prebiotic properties. Br J Nutr. 2012;108:1847-1858.
  70. Wolever TM, ter Wal P, Spadafora P, Robb P. Guar, but not psyl- lium, increases breath methane and serum acetate concentrations in human subjects. Am J Clin Nutr. 1992;55:719-722.
  71. Rahat-Rozenbloom S, Fernandes J, Cheng J, Gloor GB, Wolever TM. The acute effects of inulin and resistant starch on postpran- dial serum short-chain fatty acids and second-meal glycemic response in lean and overweight humans. Eur J Clin Nutr. 2017;71:227-233.
  72. Brown AJ, Goldsworthy SM, Barnes AA, et al. The orphan G pro- tein-coupled receptors GPR41 and GPR43 are activated by propi- onate and other short chain carboxylic acids. J Biol Chem. 2003;278:11312-11319.
  73. Ahmed K, Tunaru S, Offermanns S. GPR109A, GPR109B and GPR81, a family of hydroxy-carboxylic acid receptors. Trends Phar- macol Sci. 2009;30:557-562.
  74. Tan JK, McKenzie C, Marino E, Macia L, Mackay CR. Metabolite- sensing G protein-coupled receptors-facilitators of diet-related immune regulation. Annu Rev Immunol. 2017;35:371-402.
  75. Nohr MK, Egerod KL, Christiansen SH, et al. Expression of the short chain fatty acid receptor GPR41/FFAR3 in autonomic and somatic sensory ganglia. Neuroscience. 2015;290:126-137.
  76. Le Poul E, Loison C, Struyf S, 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- 25489.
  77. Taggart AK, Kero J, Gan X, et al. (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J Biol Chem. 2005;280:26649-26652.
  78. Sekhavat A, Sun JM, Davie JR. Competitive inhibition of histone deacetylase activity by trichostatin A and butyrate. Biochem Cell Biol. 2007;85:751-758.
  79. Park J, Kim M, Kang SG, et al. Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacety- lases and regulation of the mTOR-S6K pathway. Mucosal Immunol. 2015;8:80-93.
  80. Roediger WE. Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology. 1982;83:424-429.
  81. Sengupta S, Muir JG, Gibson PR. Does butyrate protect from col- orectal cancer? J Gastroenterol Hepatol. 2006;21:209-218.
  82. Gibson PR, Moeller I, Kagelari O, Folino M, Young GP. Contrasting effects of butyrate on the expression of phenotypic markers of dif- ferentiation in neoplastic and non-neoplastic colonic epithelial cells in vitro. J Gastroenterol Hepatol. 1992;7:165-172.
  83. Bovee-Oudenhoven IM, ten Bruggencate SJ, Lettink-Wissink ML, van der Meer R. Dietary fructo-oligosaccharides and lactulose inhi- bit intestinal colonisation but stimulate translocation of salmonella in rats. Gut. 2003;52:1572-1578.
  84. Ten Bruggencate SJ, Bovee-Oudenhoven IM, Lettink-Wissink ML, Van der Meer R. Dietary fructooligosaccharides increase intestinal permeability in rats. J Nutr. 2005;135:837-842.
  85. Ten Bruggencate SJ, Bovee-Oudenhoven IM, Lettink-Wissink ML, Katan MB, van der Meer R. Dietary fructooligosaccharides affect intestinal barrier function in healthy men. J Nutr. 2006;136:70-74.
  86. Gibson PR, Nov R, Fielding M, et al. Relationship of hydrolase activities to epithelial cell turnover in distal colonic mucosa of nor- mal rats. J Gastroenterol Hepatol. 1999;14:866-872.
  87. Young GP, McIntyre A, Albert V, Folino M, Muir JG, Gibson PR. Wheat bran suppresses potato starch-potentiated colorectal tumorigenesis at the aberrant crypt stage in a rat model. Gastroen- terology. 1996;110:508-514.
  88. Halestrap AP, Wilson MC. The monocarboxylate transporter fam- ily-role and regulation. IUBMB Life. 2012;64:109-119.
  89. Bhutia YD, Babu E, Ramachandran S, Yang S, Thangaraju M, Ganapathy V. SLC transporters as a novel class of tumour suppressors: identity, function and molecular mechanisms. Biochem J. 2016;473:1113-1124.
  90. How to cite this article: Gill PA, van Zelm MC, Muir JG, Gibson PR. Review article: short chain fatty acids as potential therapeutic agents in human gastrointestinal and inflammatory disorders. Aliment Pharmacol Ther. 2018;48: 15-34. https://doi.org/10.1111/apt.14689

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Authors
Gill, P. A., van Zelm, M. C., Muir, J. G., & Gibson, P. R.
Affiliations
  • The Alfred Hospital (AU)
  • Department of Immunology and Pathology Central Clinical School Monash University and Alfred Hospital Melbourne Vic Australia
Corresponding author
Gibson, P. R.
ORCID
Venue
Alimentary Pharmacology & Therapeutics
Publisher
Wiley
Published
2018-05-03
Volume
48
Issue
1
Pages
15-34
ISSN
  • 0269-2813 (ISSN-L)
  • 1365-2036
DOI
10.1111/apt.14689
OpenAlex
W2799848487
Cited by
520
References
21
Citations by year
2026: 49 · 2025: 67 · 2024: 73 · 2023: 70 · 2022: 82 · 2021: 68 · 2020: 63 · 2019: 39 · 2018: 9
FWCI
4.39
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Alimentary Pharmacology & Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
  • Monash University Research Portal (Monash University) (submittedVersion, other-oa)
Funders
  • Monash University
  • National Health and Medical Research Council (GNT1117687, GNT1136988)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Nursing › Nutrition and Dietetics › Microbial Metabolites in Food Biotechnology
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
Keywords
short-chain fatty acids, butyrate, propionate, acetate, dietary fiber, colonic metabolism, gut microbiota, immune regulation, inflammatory diseases, autoimmune disease, metabolic disorders, postbiotics, targeted delivery, colorectal carcinogenesis
MeSH terms
Gastrointestinal Microbiome, Animals, Dietary Fats, Dietary Fiber, Fatty Acids, Volatile, Gastrointestinal Diseases, Humans, Inflammation, Gastrointestinal Tract

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