Skip to main content
Top
Published in: Digestive Diseases and Sciences 12/2013

01-12-2013 | Original Article

Clostridium Butyricum MIYAIRI 588 Improves High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Rats

Authors: Makoto Seo, Ikuo Inoue, Mamoru Tanaka, Noriko Matsuda, Takanari Nakano, Takuya Awata, Shigehiro Katayama, David H. Alpers, Tsugikazu Komoda

Published in: Digestive Diseases and Sciences | Issue 12/2013

Login to get access

Abstract

Background/Aims

Non-alcoholic fatty liver disease (NAFLD) has become a common liver disease, as its prevalence has increased markedly in recent decades. The aim of the present study was to examine the improving effect of Clostridium butyricum MIYAIRI 588 (CBM588), a probiotic in clinical use for antibiotic-associated diarrhea, against high-fat diet (HFD)-induced fatty liver in rats.

Methods

After feeding HFD or HFD coated with CBM588 (HFD-CBM) for 12 weeks, we evaluated the hepatic mRNA levels related to lipid metabolism, and then assessed the hepatic protein levels of several transcription factors regulating these lipogenic gene expressions.

Results

The HFD-CBM group had decreased accumulation of lipid droplets in the liver compared with the HFD group. The HFD-CBM group had significantly decreased diacylglycerol acyltransferase (DGAT) 2 mRNA in the liver compared with the HFD group, whereas DGAT1 mRNA did not change between the HFD group and the HFD-CBM group. Moreover, the HFD-CBM group had significantly increased hepatic mRNA regulating cholesterol catabolism enzymes and excretion transporters. Correspondingly, the HFD-CBM588 groups had increased hepatic protein levels of peroxisome proliferator-activated receptor α/γ and liver X receptor α compared with the HFD group. The HFD-CBM group had accelerated excretion of total bile acid and non-esterified fatty acid in the feces.

Conclusions

CBM588 intake may have novel potential for improving NAFLD.
Appendix
Available only for authorised users
Literature
1.
go back to reference Adams LA, Angulo P. Recent concepts in non-alcoholic fatty liver disease. Diabet Med. 2005;22:1129–1133.PubMedCrossRef Adams LA, Angulo P. Recent concepts in non-alcoholic fatty liver disease. Diabet Med. 2005;22:1129–1133.PubMedCrossRef
2.
go back to reference Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–1321.PubMedCrossRef Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–1321.PubMedCrossRef
3.
4.
go back to reference George J, Liddle C. Nonalcoholic fatty liver disease: pathogenesis and potential for nuclear receptors as therapeutic targets. Mol Pharm. 2008;5:49–59.PubMedCrossRef George J, Liddle C. Nonalcoholic fatty liver disease: pathogenesis and potential for nuclear receptors as therapeutic targets. Mol Pharm. 2008;5:49–59.PubMedCrossRef
5.
go back to reference Yu S, Rao S, Reddy JK. Peroxisome proliferator-activated receptors, fatty acid oxidation, steatohepatitis and hepatocarcinogenesis. Curr Mol Med. 2003;3:561–572.PubMedCrossRef Yu S, Rao S, Reddy JK. Peroxisome proliferator-activated receptors, fatty acid oxidation, steatohepatitis and hepatocarcinogenesis. Curr Mol Med. 2003;3:561–572.PubMedCrossRef
6.
go back to reference Bugianesi E, Gastaldelli A, Vanni E, et al. Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms. Diabetologia. 2005;48:634–642.PubMedCrossRef Bugianesi E, Gastaldelli A, Vanni E, et al. Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms. Diabetologia. 2005;48:634–642.PubMedCrossRef
7.
go back to reference Kang H, Greenson JK, Omo JT, et al. Metabolic syndrome is associated with greater histologic severity, higher carbohydrate, and lower fat diet in patients with NAFLD. Am J Gastroenterol. 2006;101:2247–2253.PubMedCrossRef Kang H, Greenson JK, Omo JT, et al. Metabolic syndrome is associated with greater histologic severity, higher carbohydrate, and lower fat diet in patients with NAFLD. Am J Gastroenterol. 2006;101:2247–2253.PubMedCrossRef
8.
go back to reference Solga S, Alkhuraishe AR, Clark JM, et al. Dietary composition and nonalcoholic fatty liver disease. Dig Dis Sci. 2004;49:1578–1583.PubMedCrossRef Solga S, Alkhuraishe AR, Clark JM, et al. Dietary composition and nonalcoholic fatty liver disease. Dig Dis Sci. 2004;49:1578–1583.PubMedCrossRef
9.
go back to reference Benno Y, Sawada K, Mitsuoka T. The intestinal microflora of infants: composition of fecal flora in breast-fed and bottle-fed infants. Microbiol Immunol. 1984;28:975–986.PubMedCrossRef Benno Y, Sawada K, Mitsuoka T. The intestinal microflora of infants: composition of fecal flora in breast-fed and bottle-fed infants. Microbiol Immunol. 1984;28:975–986.PubMedCrossRef
10.
go back to reference Sato R, Tanaka M. Intestinal distribution and intraluminal localization of orally administered Clostridium butyricum in rats. Microbiol Immunol. 1997;41:665–671.PubMedCrossRef Sato R, Tanaka M. Intestinal distribution and intraluminal localization of orally administered Clostridium butyricum in rats. Microbiol Immunol. 1997;41:665–671.PubMedCrossRef
11.
go back to reference Ichikawa H, Kuroiwa T, Inagaki A, et al. Probiotic bacteria stimulate gut epithelial cell proliferation in rats. Dig Dis Sci. 1999;44:2119–2123.PubMedCrossRef Ichikawa H, Kuroiwa T, Inagaki A, et al. Probiotic bacteria stimulate gut epithelial cell proliferation in rats. Dig Dis Sci. 1999;44:2119–2123.PubMedCrossRef
12.
go back to reference Okamoto T, Sasaki M, Tsujikawa T, et al. Preventive efficacy of butyrate enemas and oral administration of Clostridium butyricum M588 in dextran sodium sulfate-induced colitis in rats. J Gastroenterol. 2000;35:341–346.PubMedCrossRef Okamoto T, Sasaki M, Tsujikawa T, et al. Preventive efficacy of butyrate enemas and oral administration of Clostridium butyricum M588 in dextran sodium sulfate-induced colitis in rats. J Gastroenterol. 2000;35:341–346.PubMedCrossRef
13.
go back to reference Yin L, Laevsky G, Giardina C. Butyrate suppression of colonocyte NFκB activation and cellular proteasome activity. J Biol Chem. 2001;276:44641–44646.PubMedCrossRef Yin L, Laevsky G, Giardina C. Butyrate suppression of colonocyte NFκB activation and cellular proteasome activity. J Biol Chem. 2001;276:44641–44646.PubMedCrossRef
14.
go back to reference Seki H, Shiohara M, Matsumura T, et al. Prevention of antibiotic-associated diarrhea in children by Clostridium butyricum MIYAIRI. Pediatr Int. 2003;45:86–90.PubMedCrossRef Seki H, Shiohara M, Matsumura T, et al. Prevention of antibiotic-associated diarrhea in children by Clostridium butyricum MIYAIRI. Pediatr Int. 2003;45:86–90.PubMedCrossRef
15.
go back to reference Takahashi M, Taguchi H, Yamaguchi H, et al. The effect of probiotic treatment with Clostridium butyricum on enterohemorrhagic Escherichia coli O157:H7 infection in mice. FEMS Immunol Med Microbiol. 2004;41:219–226.PubMedCrossRef Takahashi M, Taguchi H, Yamaguchi H, et al. The effect of probiotic treatment with Clostridium butyricum on enterohemorrhagic Escherichia coli O157:H7 infection in mice. FEMS Immunol Med Microbiol. 2004;41:219–226.PubMedCrossRef
16.
go back to reference Ley RE, Turnbaugh PJ, Klein S, et al. Human gut microbes associated with obesity. Nature. 2006;444:1022–1023.PubMedCrossRef Ley RE, Turnbaugh PJ, Klein S, et al. Human gut microbes associated with obesity. Nature. 2006;444:1022–1023.PubMedCrossRef
17.
go back to reference Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027–1031.PubMedCrossRef Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027–1031.PubMedCrossRef
18.
go back to reference DiBaise JK, Zhang H, Crowell MD, et al. Gut microbiota and its possible relationship with obesity. Mayo Clin Proc. 2008;83:460–469.PubMedCrossRef DiBaise JK, Zhang H, Crowell MD, et al. Gut microbiota and its possible relationship with obesity. Mayo Clin Proc. 2008;83:460–469.PubMedCrossRef
19.
go back to reference Graber CD, O’Neal RM, Rabin ER. Effect of high fat diets on intestinal microflora and serum cholesterol in rats. J Bacteriol. 1965;89:47–51.PubMed Graber CD, O’Neal RM, Rabin ER. Effect of high fat diets on intestinal microflora and serum cholesterol in rats. J Bacteriol. 1965;89:47–51.PubMed
20.
go back to reference Midtvedt T. Microbial bile acid transformation. Am J Clin Nutr. 1974;27:1341–1347.PubMed Midtvedt T. Microbial bile acid transformation. Am J Clin Nutr. 1974;27:1341–1347.PubMed
21.
go back to reference Hosomi M, Tanida N, Shimoyama T. The role of intestinal bacteria in gallstone formation in animal model. A study on biliary lipid composition and bile acid profiles in bile, small intestinal contents and feces of Clostridium butyricum MIYAIRI No. 588 monocontaminated mice. Gastroenterol Jpn. 1982;17:316–323.PubMed Hosomi M, Tanida N, Shimoyama T. The role of intestinal bacteria in gallstone formation in animal model. A study on biliary lipid composition and bile acid profiles in bile, small intestinal contents and feces of Clostridium butyricum MIYAIRI No. 588 monocontaminated mice. Gastroenterol Jpn. 1982;17:316–323.PubMed
22.
go back to reference Kobashi K, Takeda Y, Itoh H, et al. Cholesterol-lowering effect of Clostridium butyricum in cholesterol-fed rats. Digestion. 1983;26:173–178.PubMedCrossRef Kobashi K, Takeda Y, Itoh H, et al. Cholesterol-lowering effect of Clostridium butyricum in cholesterol-fed rats. Digestion. 1983;26:173–178.PubMedCrossRef
23.
go back to reference Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem. 1957;226:497–509.PubMed Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem. 1957;226:497–509.PubMed
24.
go back to reference Suzuki M, Murai T, Yoshimura T, et al. Determination of 3-oxo-Δ4- and 3-oxo-Δ4, 6-bile acids and related compounds in biological fluids of infants with cholestasis by gas chromatography-mass spectrometry. J Chromatogr B. 1997;693:11–21.CrossRef Suzuki M, Murai T, Yoshimura T, et al. Determination of 3-oxo-Δ4- and 3-oxo-Δ4, 6-bile acids and related compounds in biological fluids of infants with cholestasis by gas chromatography-mass spectrometry. J Chromatogr B. 1997;693:11–21.CrossRef
25.
go back to reference Muto A, Takai H, Unno A, et al. Detection of Δ4-3-oxo-steroid 5β-reductase deficiency by LC-ESI-MS/MS measurement of urinary bile acids. J Chromatogr B. 2012;900:24–31.CrossRef Muto A, Takai H, Unno A, et al. Detection of Δ4-3-oxo-steroid 5β-reductase deficiency by LC-ESI-MS/MS measurement of urinary bile acids. J Chromatogr B. 2012;900:24–31.CrossRef
26.
go back to reference Bach Knudsen KE, Serena A, Canibe N, et al. New insight into butyrate metabolism. Proc Nutr Soc. 2003;62:81–86. Bach Knudsen KE, Serena A, Canibe N, et al. New insight into butyrate metabolism. Proc Nutr Soc. 2003;62:81–86.
27.
go back to reference Stone SJ, Myers HM, Watkins SM, et al. Lipopenia and skin barrier abnormalities in DGAT2-deficient mice. J Biol Chem. 2003;279:11767–11776.PubMedCrossRef Stone SJ, Myers HM, Watkins SM, et al. Lipopenia and skin barrier abnormalities in DGAT2-deficient mice. J Biol Chem. 2003;279:11767–11776.PubMedCrossRef
28.
go back to reference Yamazaki T, Sasaki E, Kakinuma C, et al. Increased very low density lipoprotein secretion and gonadal fat mass in mice overexpressing liver DGAT1. J Biol Chem. 2005;280:21506–21514.PubMedCrossRef Yamazaki T, Sasaki E, Kakinuma C, et al. Increased very low density lipoprotein secretion and gonadal fat mass in mice overexpressing liver DGAT1. J Biol Chem. 2005;280:21506–21514.PubMedCrossRef
29.
go back to reference Ressell DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem. 2003;72:137–174.CrossRef Ressell DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem. 2003;72:137–174.CrossRef
30.
go back to reference Bravo E, Flora L, Cantafora A, et al. The influence of dietary saturated and unsaturated fat on hepatic cholesterol metabolism and the biliary excretion of chylomicron cholesterol in the rat. Biochim Biophys Acta. 1998;16:134–148. Bravo E, Flora L, Cantafora A, et al. The influence of dietary saturated and unsaturated fat on hepatic cholesterol metabolism and the biliary excretion of chylomicron cholesterol in the rat. Biochim Biophys Acta. 1998;16:134–148.
31.
go back to reference Shefer S, Nguyen LB, Salen G, et al. Differing effect of cholesterol and taurocholate on steady state hepatic HMG-CoA reductase and cholesterol 7 alpha-hydroxylase activities and mRNA levels in the rat. J Lipid Res. 1992;33:1193–1200.PubMed Shefer S, Nguyen LB, Salen G, et al. Differing effect of cholesterol and taurocholate on steady state hepatic HMG-CoA reductase and cholesterol 7 alpha-hydroxylase activities and mRNA levels in the rat. J Lipid Res. 1992;33:1193–1200.PubMed
32.
go back to reference Dikkers A, Tietge UJ. Biliary cholesterol secretion: more than a simple ABC. World J Gastroenterol. 2010;16:5936–5945.PubMed Dikkers A, Tietge UJ. Biliary cholesterol secretion: more than a simple ABC. World J Gastroenterol. 2010;16:5936–5945.PubMed
33.
go back to reference Figge A, Lammert F, Paigen B, et al. Hepatic overexpression of murine Abcb11 increases hepatobiliary lipid secretion and reduces hepatic steatosis. J Biol Chem. 2004;279:2790–2799.PubMedCrossRef Figge A, Lammert F, Paigen B, et al. Hepatic overexpression of murine Abcb11 increases hepatobiliary lipid secretion and reduces hepatic steatosis. J Biol Chem. 2004;279:2790–2799.PubMedCrossRef
34.
go back to reference Sun F, Xie ML, Xue J, et al. Osthol regulates hepatic PPARα-mediated lipogenic gene expression in alcoholic fatty liver murine. Phytomedicine. 2010;17:669–673.PubMedCrossRef Sun F, Xie ML, Xue J, et al. Osthol regulates hepatic PPARα-mediated lipogenic gene expression in alcoholic fatty liver murine. Phytomedicine. 2010;17:669–673.PubMedCrossRef
35.
go back to reference Gavrilova O, Haluzik M, Matsusue K, et al. Liver peroxisome proliferator-activated receptor gamma contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass. J Biol Chem. 2003;278:34268–34276.PubMedCrossRef Gavrilova O, Haluzik M, Matsusue K, et al. Liver peroxisome proliferator-activated receptor gamma contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass. J Biol Chem. 2003;278:34268–34276.PubMedCrossRef
36.
go back to reference Kota BP, Huang TH, Roufogalis BD. An overview on biological mechanisms of PPARs. Pharmacol Res. 2005;51:85–94.PubMedCrossRef Kota BP, Huang TH, Roufogalis BD. An overview on biological mechanisms of PPARs. Pharmacol Res. 2005;51:85–94.PubMedCrossRef
37.
go back to reference Chinetti G, Lestavel S, Bocher V, et al. R-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med. 2001;7:53–58.PubMedCrossRef Chinetti G, Lestavel S, Bocher V, et al. R-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med. 2001;7:53–58.PubMedCrossRef
38.
go back to reference Ogata M, Tsujita M, Hossain MA, et al. On the mechanism for PPAR agonists to enhance ABCA1 gene expression. Atherosclerosis. 2009;205:413–419.PubMedCrossRef Ogata M, Tsujita M, Hossain MA, et al. On the mechanism for PPAR agonists to enhance ABCA1 gene expression. Atherosclerosis. 2009;205:413–419.PubMedCrossRef
39.
go back to reference Kalaany NY, Mangelsdorf DJ. LXRs and FXR: the yin and yang of cholesterol and fat metabolism. Annu Rev Physiol. 2006;68:159–191.PubMedCrossRef Kalaany NY, Mangelsdorf DJ. LXRs and FXR: the yin and yang of cholesterol and fat metabolism. Annu Rev Physiol. 2006;68:159–191.PubMedCrossRef
40.
go back to reference Trauner M, Halilbasic E. Nuclear receptors as new perspective for the management of liver diseases. Gastroenterology. 2011;140:1120–1125.PubMedCrossRef Trauner M, Halilbasic E. Nuclear receptors as new perspective for the management of liver diseases. Gastroenterology. 2011;140:1120–1125.PubMedCrossRef
Metadata
Title
Clostridium Butyricum MIYAIRI 588 Improves High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Rats
Authors
Makoto Seo
Ikuo Inoue
Mamoru Tanaka
Noriko Matsuda
Takanari Nakano
Takuya Awata
Shigehiro Katayama
David H. Alpers
Tsugikazu Komoda
Publication date
01-12-2013
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 12/2013
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-013-2879-3

Other articles of this Issue 12/2013

Digestive Diseases and Sciences 12/2013 Go to the issue