Sodium butyrate - therapeutic signposts Review article
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Published:
Mar 31, 2024
Keywords:
sodium butyrate, short chain fatty acids, irritable bowel syndrome
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Abstract
Sodium butyrate is the sodium salt of butyric acid, a short-chain fatty acid, which has strong trophic effect on the intestinal epithelium. The impact of sodium butyrate supplementation is area of interest in many fields of medicine: gastroenterology, diabetology and oncology. Its beneficial effects have been most widely described in alleviating the symptoms of irritable bowel syndrome. Literature also describes its impact on carbohydrate metabolism and the treatment of inflammatory bowel diseases.
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Panufnik, P., Banasiewicz, T., & Rydzewska, G. (2024). Sodium butyrate - therapeutic signposts. Medycyna Faktow (J EBM), 17(1(62), 121-128. https://doi.org/10.24292/01.MF.0124.19
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References
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2. Tsukahara T, Koyama H, Okada M et al. Stimulation of butyrate production by gluconic acid in batch culture of pig cecal digesta and identification of butyrateproducing bacteria. J Nutr. 2002; 132: 222934.
3. Kiani AK, Medori MC, Bonetti G et al. Modern vision of the Mediterranean diet. J Prev Med Hyg. 2022; 63(2 Suppl 3): E36-43.
4. Newsome R, Yang Y, Jobin C. Western diet influences on microbiome and carcinogenesis. Semin Immunol. 2023; 67: 101756.
5. García-Montero C, Fraile-Martínez O, Gómez-Lahoz AM et al. Nutritional Components in Western Diet Versus Mediterranean Diet at the Gut Microbiota-Immune System Interplay. Implications for Health and Disease. Nutrients. 2021; 13(2): 699.
6. Coppola S, Avagliano C, Calignano A et al. The Protective Role of Butyrate against Obesity and Obesity-Related Diseases. Molecules. 2021; 26: 682.
7. Banasiewicz T. Badanie porównujące profil uwalniania się w jelicie aktualnie dostępnych na rynku polskim produktów zawierających maślan sodu. Med Fakt. 2017; 4(37).
8. Chapman MA, Grahn MF, Boyle MA et al. Butyrate oxidation is impaired in the colonic mucosa of sufferers of quiescent ulcerative colitis. Gut. 1994; 35(1): 73-6.
9. Tarnowski W, Borycka-Kiciak K, Kiciak A et al. Efekty leczenia kwasem masłowym w zespole jelita drażliwego – doniesienie wstępne. Gastroenterol Prakt. 2013; 1 : 43-8.
10. Leonel AJ, Alvarez-Leite JI. Butyrate: implications for intestinal function. Curr Opin Clin Nutr Metab Care. 2012; 15(5): 474-9.
11. Załęski A, Banaszkiewicz A, Walkowiak J. Butyric acid in irritable bowel syndrome. Prz Gastroenterol. 2013; 15(2): 204-49.
12. Pozuelo M, Panda S, Santiago A et al. Reduction of butyrate- and methane-producing microorganisms in patients with Irritable Bowel Syndrome. Sci Rep. 2015; 5: 12693.
13. Banasiewicz T, Krokowicz Ł, Stojcev Z et al. Microencapsulated sodium butyrate reduces the frequency of abdominal pain in patients with irritable bowel syndrome. Colorectal Dis. 2013; 15(2): 204-9.
14. Lewandowski K, Kaniewska M, Karłowicz K et al. The effectiveness of microencapsulated sodium butyrate at reducing symptoms in patients with irritable bowel syndrome. Prz Gastroenterol. 2022; 17(1): 28-34.
15. Parada Venegas D, De la Fuente MK, Landskron G et al. Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. Front Immunol. 2019; 10: 277.
16. Deleu S, Machiels K, Raes J et al. Short chain fatty acids and its producing organisms: An overlooked therapy for IBD? EBioMedicine. 2021; 66: 103293.
17. Facchin S, Vitulo N, Calgaro M et al. Microbiota changes induced by microencapsulated sodium butyrate in patients with inflammatory bowel disease. Neurogastroenterol Motil. 2020; 32(10): e13914.
18. Pietrzak A, Banasiuk M, Szczepanik M et al. Sodium Butyrate Effectiveness in Children and Adolescents with Newly Diagnosed Inflammatory Bowel Diseases-Randomized Placebo-Controlled Multicenter Trial. Nutrients. 2022; 14(16): 3283.
19. Karłowicz K, Lewandowski K, Tulewicz-Marti E et al. P876 Efficacy and safety of microencapsulated butyrate add-on therapy in induction of remission in patients with mild-to-moderate Ulcerative Colitis – results from multi-center, double-blind, randomized, placebo-controlled clinical study. Journal of Crohn’s and Colitis. 2024; 18(1): i1618.
20. Krokowicz L, Stojcev Z, Kaczmarek BF et al. Microencapsulated sodium butyrate administered to patients with diverticulosis decreases incidence of diverticulitis – a prospective randomized study. Int J Colorectal Dis. 2014; 29(3): 387-93.
21. Bajka BH, Clarke JM, Topping DL et al. Butyrylated starch increases large bowel butyrate levels and lowers colonic smooth muscle contractility in rats. Nut Res. 2010; 30: 427-34.
22. Hodgkinson K, El Abbar F, Dobranowski P et al. Butyrate’s role in human health and the current progress towards its clinical application to treat gastrointestinal disease. Clin Nutr. 2023; 42(2): 61-75.
23. Tseng CH, Wu CY. The gut microbiome in obesity. J Formos Med Assoc. 2019; 118(Suppl 1): S3-S9.
24. van Deuren T, Blaak EE, Canfora EE. Butyrate to combat obesity and obesity-associated metabolic disorders: Current status and future implications for therapeutic use. Obes Rev. 2022; 23(10): e13498.
25. Zhou D, Chen YW, Zhao ZH et al. Sodium butyrate reduces high-fat diet-induced non-alcoholic steatohepatitis through upregulation of hepatic GLP-1R expression. Exp Mol Med. 2018; 50(12): 1-12.
26. Khan S, Jena G. Sodium butyrate reduces insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat: A comparative study with metformin. Chem Biol Interact. 2016; 254: 124-34.
27. Park M, Kwon J, Shin HJ et al. Butyrate enhances the efficacy of radiotherapy via FOXO3A in colorectal cancer patientderived organoids. Int J Oncol. 2020; 57(6): 1307-18.
28. Encarnação JC, Pires AS, Amaral RA et al. Butyrate, a dietary fiber derivative that improves irinotecan effect in colon cancer cells. J Nutr Biochem. 2018; 56: 183-92.
29. Xi Y, Jing Z, Wei W et al. Inhibitory effect of sodium butyrate on colorectal cancer cells and construction of the related molecular network. BMC Cancer. 2021; 21(1): 127.
30. Pinto A, Fidalgo P, Cravo M et al. Short chain fatty acids are effective in short-term treatment of chronic radiation proctitis: randomized, double- blind, controlled trial. Dis Colon Rectum. 1999; 42(6): 788-95.
31. Harig JM, Soergel KH, Komorowski RA et al. Treatment of diversion colitis with short-chain-fatty acid irrigation. N Engl J Med. 1989; 320(1): 23-8.
32. Mortensen FV, Hessov I, Birke H et al. Microcirculatory and trophic effects of short chain fatty acids in the human rectum after Hartmann’s procedure. Br J Surg. 1991; 78(10): 1208-11.
33. Brown AJ, Goldsworthy SM, Barnes AA 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(13): 11312-9.
34. Nilsson NE, Kotarsky K, Owman C et al. 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.
35. Tolhurst G, Heffron H, Lam YS et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2012; 61(2): 364-71.
36. Yadav H, Lee JH, Lloyd J et al. Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion. J Biol Chem. 2013; 288(35): 25088-97.
37. Nohr MK, Pedersen MH, Gille A et al. GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes. Endocrinology. 2013; 154(10): 3552-64.
38. Khan S, Jena G. Sodium butyrate reduces insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat: A comparative study with metformin. Chem Biol Interact. 2016; 254: 124-34.
39. Roshanravan N, Mahdavi R, Alizadeh E et al. Effect of Butyrate and Inulin Supplementation on Glycemic Status, Lipid Profile and Glucago-Like Peptide 1 Level in Patients with Type 2 Diabetes: A Randomized Double-Blind, Placebo-Controlled Trial. Horm Metab Res. 2017; 49(11): 886-91.
40. Coppola S, Nocerino R, Paparo L et al. Butyrate against paediatric obesity: results of the BAPO trial. Nutr Metab Cardiovasc Dis. 2021; 31: 3249.
41. Bouter K, Bakker GJ, Levin E et al. Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects. Clin Transl Gastroenterol. 2018; 9(5): 155.
42. Gill PA, van Zelm MC, Muir JG et al. Review article: short chain fatty acids as potential therapeutic agents in human gastrointestinal and inflammatory disorders. Aliment Pharmacol Ther. 2018; 48(1): 15-34.
43. Panufnik P, Więcek M, Szwarc P et al. The effects of sodium butyrate supplementation on the severity of abdominal symptoms and carbohydrate metabolism in patients with type 2 diabetes – preliminary data. United European Gastroenterology Journal. 2023; 11(8).
44. Banasiewicz T, Kobiela J, Cwaliński J et al. Rekomendacje w zakresie stosowania prehabilitacji, czyli kompleksowego przygotowania pacjenta do zabiegu operacyjnego. Pol Przegl Chirurg. 2023; 95(4): 62-91.
45. Trone K, Rahman S, Green CH et al. Synbiotics and Surgery: Can Prebioticsand Probiotics Affect Inflammatory Surgical Outcomes? Curr Nutr Rep. 2023; 12(2): 238-46.
46. Motoori M, Tanaka K, Sugimura K et al. Impact of preoperative fecal shortchain fatty acids on postoperative infectious complications in esophageal cancerpatients. BMC Gastroenterol. 2020; 20(1): 74.
47. Hyoju SK, Adriaansens C, Wienholts K et al. Low-fat/high-fibre diet prehabilitationimproves anastomotic healing via the microbiome: an experimental model.Br J Surg. 2020; 107(6): 743-55.
48. Zhang Y, Xu S, Qian Y et al. Sodium butyrate ameliorates gut dysfunction and motor deficits in a mouse model of Parkinson’s disease by regulating gut microbiota. Front Aging Neurosci. 2023; 15: 1099018.
49. Doifode T, Giridharan VV, Generoso JS et al. The impact of the microbiota-gut-brain axis on Alzheimer’s disease pathophysiology. Pharmacol Res. 2021; 164: 105314.
50. Szentirmai É, Millican NS, Massie AR et al. Butyrate, a metabolite of intestinal bacteria, enhances sleep. Sci Rep. 2019; 9(1): 7035.
51. Li Y, Li H, Wang R et al. Protective effect of sodium butyrate on intestinal barrier damage and uric acid reduction in hyperuricemia mice. Biomed Pharmacother. 2023; 161: 114568.
52. Vinarskaya AK, Balaban PM, Roshchin MV et al. Sodium butyrate as a selective cognitive enhancer for weak or impaired memory. Neurobiol Learn Mem. 2021; 180: 107414.
53. Lawrance IC. Topical agents for idiopathic distal colitis and proctitis. J Gastroenterol Hepatol. 2011; 26(1): 36-43.
54. Banasiewicz T, Domagalska D, Borycka-Kiciak K et al. Determination of butyric acid dosage based on clinical and experimental studies – a literature review. Prz Gastroenterol. 2020; 15(2): 119-25.
2. Tsukahara T, Koyama H, Okada M et al. Stimulation of butyrate production by gluconic acid in batch culture of pig cecal digesta and identification of butyrateproducing bacteria. J Nutr. 2002; 132: 222934.
3. Kiani AK, Medori MC, Bonetti G et al. Modern vision of the Mediterranean diet. J Prev Med Hyg. 2022; 63(2 Suppl 3): E36-43.
4. Newsome R, Yang Y, Jobin C. Western diet influences on microbiome and carcinogenesis. Semin Immunol. 2023; 67: 101756.
5. García-Montero C, Fraile-Martínez O, Gómez-Lahoz AM et al. Nutritional Components in Western Diet Versus Mediterranean Diet at the Gut Microbiota-Immune System Interplay. Implications for Health and Disease. Nutrients. 2021; 13(2): 699.
6. Coppola S, Avagliano C, Calignano A et al. The Protective Role of Butyrate against Obesity and Obesity-Related Diseases. Molecules. 2021; 26: 682.
7. Banasiewicz T. Badanie porównujące profil uwalniania się w jelicie aktualnie dostępnych na rynku polskim produktów zawierających maślan sodu. Med Fakt. 2017; 4(37).
8. Chapman MA, Grahn MF, Boyle MA et al. Butyrate oxidation is impaired in the colonic mucosa of sufferers of quiescent ulcerative colitis. Gut. 1994; 35(1): 73-6.
9. Tarnowski W, Borycka-Kiciak K, Kiciak A et al. Efekty leczenia kwasem masłowym w zespole jelita drażliwego – doniesienie wstępne. Gastroenterol Prakt. 2013; 1 : 43-8.
10. Leonel AJ, Alvarez-Leite JI. Butyrate: implications for intestinal function. Curr Opin Clin Nutr Metab Care. 2012; 15(5): 474-9.
11. Załęski A, Banaszkiewicz A, Walkowiak J. Butyric acid in irritable bowel syndrome. Prz Gastroenterol. 2013; 15(2): 204-49.
12. Pozuelo M, Panda S, Santiago A et al. Reduction of butyrate- and methane-producing microorganisms in patients with Irritable Bowel Syndrome. Sci Rep. 2015; 5: 12693.
13. Banasiewicz T, Krokowicz Ł, Stojcev Z et al. Microencapsulated sodium butyrate reduces the frequency of abdominal pain in patients with irritable bowel syndrome. Colorectal Dis. 2013; 15(2): 204-9.
14. Lewandowski K, Kaniewska M, Karłowicz K et al. The effectiveness of microencapsulated sodium butyrate at reducing symptoms in patients with irritable bowel syndrome. Prz Gastroenterol. 2022; 17(1): 28-34.
15. Parada Venegas D, De la Fuente MK, Landskron G et al. Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. Front Immunol. 2019; 10: 277.
16. Deleu S, Machiels K, Raes J et al. Short chain fatty acids and its producing organisms: An overlooked therapy for IBD? EBioMedicine. 2021; 66: 103293.
17. Facchin S, Vitulo N, Calgaro M et al. Microbiota changes induced by microencapsulated sodium butyrate in patients with inflammatory bowel disease. Neurogastroenterol Motil. 2020; 32(10): e13914.
18. Pietrzak A, Banasiuk M, Szczepanik M et al. Sodium Butyrate Effectiveness in Children and Adolescents with Newly Diagnosed Inflammatory Bowel Diseases-Randomized Placebo-Controlled Multicenter Trial. Nutrients. 2022; 14(16): 3283.
19. Karłowicz K, Lewandowski K, Tulewicz-Marti E et al. P876 Efficacy and safety of microencapsulated butyrate add-on therapy in induction of remission in patients with mild-to-moderate Ulcerative Colitis – results from multi-center, double-blind, randomized, placebo-controlled clinical study. Journal of Crohn’s and Colitis. 2024; 18(1): i1618.
20. Krokowicz L, Stojcev Z, Kaczmarek BF et al. Microencapsulated sodium butyrate administered to patients with diverticulosis decreases incidence of diverticulitis – a prospective randomized study. Int J Colorectal Dis. 2014; 29(3): 387-93.
21. Bajka BH, Clarke JM, Topping DL et al. Butyrylated starch increases large bowel butyrate levels and lowers colonic smooth muscle contractility in rats. Nut Res. 2010; 30: 427-34.
22. Hodgkinson K, El Abbar F, Dobranowski P et al. Butyrate’s role in human health and the current progress towards its clinical application to treat gastrointestinal disease. Clin Nutr. 2023; 42(2): 61-75.
23. Tseng CH, Wu CY. The gut microbiome in obesity. J Formos Med Assoc. 2019; 118(Suppl 1): S3-S9.
24. van Deuren T, Blaak EE, Canfora EE. Butyrate to combat obesity and obesity-associated metabolic disorders: Current status and future implications for therapeutic use. Obes Rev. 2022; 23(10): e13498.
25. Zhou D, Chen YW, Zhao ZH et al. Sodium butyrate reduces high-fat diet-induced non-alcoholic steatohepatitis through upregulation of hepatic GLP-1R expression. Exp Mol Med. 2018; 50(12): 1-12.
26. Khan S, Jena G. Sodium butyrate reduces insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat: A comparative study with metformin. Chem Biol Interact. 2016; 254: 124-34.
27. Park M, Kwon J, Shin HJ et al. Butyrate enhances the efficacy of radiotherapy via FOXO3A in colorectal cancer patientderived organoids. Int J Oncol. 2020; 57(6): 1307-18.
28. Encarnação JC, Pires AS, Amaral RA et al. Butyrate, a dietary fiber derivative that improves irinotecan effect in colon cancer cells. J Nutr Biochem. 2018; 56: 183-92.
29. Xi Y, Jing Z, Wei W et al. Inhibitory effect of sodium butyrate on colorectal cancer cells and construction of the related molecular network. BMC Cancer. 2021; 21(1): 127.
30. Pinto A, Fidalgo P, Cravo M et al. Short chain fatty acids are effective in short-term treatment of chronic radiation proctitis: randomized, double- blind, controlled trial. Dis Colon Rectum. 1999; 42(6): 788-95.
31. Harig JM, Soergel KH, Komorowski RA et al. Treatment of diversion colitis with short-chain-fatty acid irrigation. N Engl J Med. 1989; 320(1): 23-8.
32. Mortensen FV, Hessov I, Birke H et al. Microcirculatory and trophic effects of short chain fatty acids in the human rectum after Hartmann’s procedure. Br J Surg. 1991; 78(10): 1208-11.
33. Brown AJ, Goldsworthy SM, Barnes AA 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(13): 11312-9.
34. Nilsson NE, Kotarsky K, Owman C et al. 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.
35. Tolhurst G, Heffron H, Lam YS et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2012; 61(2): 364-71.
36. Yadav H, Lee JH, Lloyd J et al. Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion. J Biol Chem. 2013; 288(35): 25088-97.
37. Nohr MK, Pedersen MH, Gille A et al. GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes. Endocrinology. 2013; 154(10): 3552-64.
38. Khan S, Jena G. Sodium butyrate reduces insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat: A comparative study with metformin. Chem Biol Interact. 2016; 254: 124-34.
39. Roshanravan N, Mahdavi R, Alizadeh E et al. Effect of Butyrate and Inulin Supplementation on Glycemic Status, Lipid Profile and Glucago-Like Peptide 1 Level in Patients with Type 2 Diabetes: A Randomized Double-Blind, Placebo-Controlled Trial. Horm Metab Res. 2017; 49(11): 886-91.
40. Coppola S, Nocerino R, Paparo L et al. Butyrate against paediatric obesity: results of the BAPO trial. Nutr Metab Cardiovasc Dis. 2021; 31: 3249.
41. Bouter K, Bakker GJ, Levin E et al. Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects. Clin Transl Gastroenterol. 2018; 9(5): 155.
42. Gill PA, van Zelm MC, Muir JG et al. Review article: short chain fatty acids as potential therapeutic agents in human gastrointestinal and inflammatory disorders. Aliment Pharmacol Ther. 2018; 48(1): 15-34.
43. Panufnik P, Więcek M, Szwarc P et al. The effects of sodium butyrate supplementation on the severity of abdominal symptoms and carbohydrate metabolism in patients with type 2 diabetes – preliminary data. United European Gastroenterology Journal. 2023; 11(8).
44. Banasiewicz T, Kobiela J, Cwaliński J et al. Rekomendacje w zakresie stosowania prehabilitacji, czyli kompleksowego przygotowania pacjenta do zabiegu operacyjnego. Pol Przegl Chirurg. 2023; 95(4): 62-91.
45. Trone K, Rahman S, Green CH et al. Synbiotics and Surgery: Can Prebioticsand Probiotics Affect Inflammatory Surgical Outcomes? Curr Nutr Rep. 2023; 12(2): 238-46.
46. Motoori M, Tanaka K, Sugimura K et al. Impact of preoperative fecal shortchain fatty acids on postoperative infectious complications in esophageal cancerpatients. BMC Gastroenterol. 2020; 20(1): 74.
47. Hyoju SK, Adriaansens C, Wienholts K et al. Low-fat/high-fibre diet prehabilitationimproves anastomotic healing via the microbiome: an experimental model.Br J Surg. 2020; 107(6): 743-55.
48. Zhang Y, Xu S, Qian Y et al. Sodium butyrate ameliorates gut dysfunction and motor deficits in a mouse model of Parkinson’s disease by regulating gut microbiota. Front Aging Neurosci. 2023; 15: 1099018.
49. Doifode T, Giridharan VV, Generoso JS et al. The impact of the microbiota-gut-brain axis on Alzheimer’s disease pathophysiology. Pharmacol Res. 2021; 164: 105314.
50. Szentirmai É, Millican NS, Massie AR et al. Butyrate, a metabolite of intestinal bacteria, enhances sleep. Sci Rep. 2019; 9(1): 7035.
51. Li Y, Li H, Wang R et al. Protective effect of sodium butyrate on intestinal barrier damage and uric acid reduction in hyperuricemia mice. Biomed Pharmacother. 2023; 161: 114568.
52. Vinarskaya AK, Balaban PM, Roshchin MV et al. Sodium butyrate as a selective cognitive enhancer for weak or impaired memory. Neurobiol Learn Mem. 2021; 180: 107414.
53. Lawrance IC. Topical agents for idiopathic distal colitis and proctitis. J Gastroenterol Hepatol. 2011; 26(1): 36-43.
54. Banasiewicz T, Domagalska D, Borycka-Kiciak K et al. Determination of butyric acid dosage based on clinical and experimental studies – a literature review. Prz Gastroenterol. 2020; 15(2): 119-25.