益生菌和小檗碱对肠道菌群失调诱导糖尿病预防的研究
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摘要
糖尿病是一组以慢性高血糖为特征的代谢性疾病。肠道菌群是一个复杂的微生物群落,存在于胃肠道生态系统中,其变化不仅影响各种肠道疾病,而且影响糖尿病。许多研究表明,糖尿病患者肠道菌群的组成发生了变化。益生菌和小檗碱可通过改变肠道菌群及其代谢产物,减轻低水平慢性炎性反应、改善短链脂肪酸和胆汁酸的代谢,成为预防和改善糖尿病的常用药物。笔者概述了益生菌和小檗碱对肠道菌群的影响和改善糖尿病的研究进展,为今后糖尿病的相关研究提供理论依据和思路。
Diabetes mellitus is a group of metabolic diseases characterized by chronic hyperglycemia. Intestinal flora is a complex microbial community, which exists in the gastrointestinal ecosystem. Its changes not only affect various intestinal diseases, but also affect diabetes. Many studies have shown that the composition of intestinal flora in diabetic patients has changed. Probiotics and berberine are commonly used drugs to prevent and improve diabetes by altering intestinal flora and its metabolites, alleviating low-level chronic inflammation and improving the metabolism of short-chain fatty acids and bile acids. In this study, the effects of probiotics and berberine on intestinal flora and the progress of diabetes mellitus improvement were summarized, which provided theoretical basis and ideas for future research on diabetes mellitus.
Diabetes mellitus is a group of metabolic diseases characterized by chronic hyperglycemia. Intestinal flora is a complex microbial community, which exists in the gastrointestinal ecosystem. Its changes not only affect various intestinal diseases, but also affect diabetes. Many studies have shown that the composition of intestinal flora in diabetic patients has changed. Probiotics and berberine are commonly used drugs to prevent and improve diabetes by altering intestinal flora and its metabolites, alleviating low-level chronic inflammation and improving the metabolism of short-chain fatty acids and bile acids. In this study, the effects of probiotics and berberine on intestinal flora and the progress of diabetes mellitus improvement were summarized, which provided theoretical basis and ideas for future research on diabetes mellitus.
引文
[1]Velmurugan G,Ramprasath T,Gilles M,et al.Gut microbiota,endocrine disrupting chemicals,and the diabetes epidemic[J].Trends in Endocrinol Metab,2017,28(8):612-625.DOI:10.1016/j.tem.2017.05.001.
[2]Sedighi M,Razavi S,Navab-Moghadam F,et al.Comparison of gut microbiota in adult patients with type 2diabetes and healthy individuals[J].Microb Pathog,2017(111):362-369.DOI:10.1016/j.micpath.2017.08.038.
[3]Tuddenham S,Sears C L.The intestinal microbiome and health[J].Curr Opin Infect Dis,2015,28(5):464-470.DOI:10.1097/QCO.0000000000000196.
[4]Shin N R,Whon T W,Bae J W.Proteobacteria:microbial signature of dysbiosis in gut microbiota[J].Trends Biotechnol,2015,33(9):496-503.DOI:10.1016/j.tibtech.2015.06.011.
[5]Mu?oz-Garach A,Diaz-Perdigones C,Tinahones FJ.Gut microbiota and type 2 diabetss mellitus[J].Endocrinol Nutr,2016,63(10):560-568.DOI:10.1016/j.endonu.2016.07.008.
[6]LêK A,Li Y,Xu X,et al.Alterations in fecal Lactobacillus and Bifidobacterium species in type 2diabetic patients in Southern China population[J].Front Physiol,2013(3):496.DOI:10.3389/fphys.2012.00496.
[7]Sonne D P,Hansen M,Knop F K.Bile acid sequestrants in type 2 diabetes:potential effects on GLP1 secretion[J].Eur J Endocrinol,2014,171(2):R47-R65.DOI:10.1530/EJE-14-0154.
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[9]Corrêa-Oliveira R,Fachi J L,Vieira A,et al.Regulation of immune cell function by short-chain fatty acids[J].Clin Transl Immunology,2016,5(4):e73.DOI:10.1038/cti.2016.17.
[10]Canfora E E,Jocken J W,Blaak E E.Short-chain fatty acids in control of body weight and insulin sensitivity[J].Nat Rev Endocrinol,2015,11(10):577-591.DOI:10.1038/nrendo.2015.128.
[11]Shapiro H,Kolodziejczyk A A,Halstuch D,et al.Bile acids in glucose metabolism in health and disease[J].J Exp Med,2018,215(2):383-396.DOI:10.1084/jem.20171965.
[12]Gomes A C,Bueno A A,de Souza R G.Gut microbiota,probiotics and diabetes[J].Nutr J,2014(13):60.DOI:10.1186/1475-2891-13-60.
[13]Samah S,Ramasamy K,Lim S M,et al.Probiotics for the management of type 2 diabetes mellitus:A systematic review and meta-analysis[J].Diabetes Res Clin Prac,2016(118):172-182.DOI:10.1016/j.diabres.2016.06.014.
[14]Sonnenburg J L,Chen C T,Gordon J I.Genomic and metabolic studies of the impact of probiotics on a model gut symbiont and host[J].PLoS Biol,2016,4(12):e413.DOI:10.1371/journal.pbio.0040413.
[15]Jayashree B,Bibin Y S,Prabhu D,et al.Increased circulatory levels of lipopolysaccharide(LPS)and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes[J].Mol Cell Biochem,2014,388(1-2):203-210.DOI:10.1007/s11010-013-1911-4.
[16]Amar J,Chabo C,Waget A,et al.Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes:molecular mechanisms and probiotic treatment[J].EMBO Mol Med,2011,3(9):559-572.DOI:10.1002/emmm.201100159.
[17]Chen P,Zhang Q,Dang H,et al.Oral administration of Lactobacillus rhamnosus CCFM0528 improves glucose tolerance and cytokine secretion in high-fatfed,streptozotocin-induced type 2 diabetic mice[J].JFUNCT FOODS,2014(10):318-326.DOI:10.1016/j.jff.2014.06.014.
[18]LeBlanc J G,Chain F,Martín R,et al.Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria[J].Microb Cell Fact,2017,16(1):79.DOI:10.1186/s12934-017-0691-z.
[19]Angelakis E,Merhej V,Raoult D.Related action of probiotics and antibiotics on gut microbiota and weight modification[J].Lancet Infect Dis,2013,13(10):889-899.DOI:10.1016/S1473-3099(13)70179-8.
[20]Kadooka Y,Sato M,Imaizumi K,et al.Regulation of abdominal adiposity by probiotics(Lactobacillus gasseri SBT2055)in adults with obese tendencies in a randomized controlled trial[J].Eur J Clin Nutr,2010,64(6):636-643.DOI:10.1038/ejcn.2010.19.
[21]Wang L,Zhang J,Guo Z,et al.Effect of oral consumption of probiotic Lactobacillus planatarum P-8 on fecal microbiota,SIgA,SCFAs,and TBAs of adults of different ages[J].Nutrition,2014,30(7-8):776-783.DOI:10.1016/j.nut.2013.11.018.
[22]Kaji I,Karaki S,Tanaka R,et al.Density distribution of free fatty acid receptor 2(FFA2)-expressing and GLP-1-producing enteroendocrine L cells in human and rat lower intestine,and increased cell numbers after ingestion of fructo-oligosaccharide[J].J Mol Histol,2011,42(1):27-38.DOI:10.1007/s10735-010-9304-4.
[23]Balakumar M,Prabhu D,Sathishkumar C,et al.Improvement in glucose tolerance and insulin sensitivity by probiotic strains of Indian gut origin in high-fat diet-fed C57BL/6J mice[J].Eur J Nutr,2018,57(1):279-295.DOI:10.1007/s00394-016-1317-7.
[24]Simon M C,Strassburger K,Nowotny B,et al.Intake of lactobacillus reuteri improves incretin and insulin secretion in glucose-tolerant humans:a proof of concept[J].Diabetes Care,2015,38(10):1827-1834.DOI:10.2337/dc14-2690.
[25]Reis S A,Concei??o L L,Rosa D D,et al.Mechanisms responsible for the hypocholesterolaemic effect of regular consumption of probiotics[J].Nutr Res Rev,2017,30(1):36-49.DOI:10.1017/S0954422416000226.
[26]Pedersen C,Lefevre S,Peters V,et al.Gut hormone release and appetite regulation in healthy non-obese participants following oligofructose intake.A dose-escalation study[J].Appetite,2014(66):44-53.DOI:10.1016/j.appet.2013.02.017.
[27]Ishimwe N,Daliri E B,Lee B H,et al.The perspective on cholesterol-lowering mechanisms of probiotics[J].Mol Nutr Food Res,2015,59(1):94-105.DOI:10.1002/mnfr.201400548.
[28]Kadooka Y,Sato M,Imaizumi K,et al.Regulation of abdominal adiposity by probiotics(Lactobacillus gasseri SBT2055)in adults with obese tendencies in a randomized controlled trial[J].Eur J Clin Nutr,2010,64(6):636-643.DOI:10.1038/ejcn.2010.19.
[29]Kumar A,Ekavali,Chopra K,et al.Current knowledge and pharmacological profile of berberine:An update[J].Eur J Pharmacol,2015(761):288-297.DOI:10.1016/j.ejphar.2015.05.068.
[30]Iwasa K,Moriyasu M,Nader B.Fungicidal and berbicidal activities of berberine related alkaloids[J].Biosci Biotechnol Biochem,2000,64(9):1998-2000.DOI:10 .1271/bbb.64.1998.
[31]崔祥,陶金华,江曙,等.小檗碱与肠道菌群的相互作用研究[J].中国微生态学杂志,2017,29(12):1373-1377.DOI:10.13381/j.cnki.cjm.201712002.
[32]Pan G Y,Wang G J,Liu X D,et al.The involvement of P-glycoprotein in berberine absorption[J].Pharmacol Toxicol,2002,91(4):193-197.
[33]黄兴,李艳芬,寇冠军,等.小檗碱抗动脉粥样硬化作用机制研究进展[J].药物评价研究,2016,39(3):469-473.DOI:10.7501/j.issn.1674-6376.2016.03.029.
[34]Imenshahidi M,Hosseinzadeh H.Berberis vulgaris and berberine:An update review[J].Phytother Res,2016,30(11):1745-1764.DOI:10.1002/ptr.5693.
[35]候丽琼,赵铁耘,张伊祎.黄连素对肥胖胰岛素抵抗大鼠骨骼肌胰岛素抵抗的干预研究[J].四川大学学报(医学版),2015,46(6):827-831.
[36]Lee Y S,Kim W S,Kim K H.Berberine,a natural plant product,activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulinresistant states[J].Diabetes,2006,55(8):2256-2264.DOI:10.2337/db06-0006.
[37]Wang Y,Shou J W,Li X Y,et al.Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism[J].Metabolism,2017(70):72-84.DOI:10.1016/j.metabol.2017.02.003.
[38]Moghaddam H K,Baluchnejadmojarad T,Roghani M.Berberine ameliorate oxidative stress and astrogliosis in the hippocampus of STZ-induced diabetic rats[J].Mol Neurobiol,2014,49(2):820-826.DOI:10.1007/s12035-013-8559-7.
[39]Zhang Y,Limaye P B,Lehman-McKeeman L D,et al.Dysfunction of organic anion transporting polypeptide1a1 alters intestinal bacteria and bile acid metabolism in mice[J].PLoS One,2012,7(4):e34522.DOI:10.1371/journal.pone.0034522.
[40]Memon M A,Khan R N,Riaz S,et al.Methylglyoxal and insulin resistance in berberine-treated type 2 diabetic patients[J].J Res Med Sci,2018(23):110.DOI:10.4103/jrms.JRMS_1078_17.
[2]Sedighi M,Razavi S,Navab-Moghadam F,et al.Comparison of gut microbiota in adult patients with type 2diabetes and healthy individuals[J].Microb Pathog,2017(111):362-369.DOI:10.1016/j.micpath.2017.08.038.
[3]Tuddenham S,Sears C L.The intestinal microbiome and health[J].Curr Opin Infect Dis,2015,28(5):464-470.DOI:10.1097/QCO.0000000000000196.
[4]Shin N R,Whon T W,Bae J W.Proteobacteria:microbial signature of dysbiosis in gut microbiota[J].Trends Biotechnol,2015,33(9):496-503.DOI:10.1016/j.tibtech.2015.06.011.
[5]Mu?oz-Garach A,Diaz-Perdigones C,Tinahones FJ.Gut microbiota and type 2 diabetss mellitus[J].Endocrinol Nutr,2016,63(10):560-568.DOI:10.1016/j.endonu.2016.07.008.
[6]LêK A,Li Y,Xu X,et al.Alterations in fecal Lactobacillus and Bifidobacterium species in type 2diabetic patients in Southern China population[J].Front Physiol,2013(3):496.DOI:10.3389/fphys.2012.00496.
[7]Sonne D P,Hansen M,Knop F K.Bile acid sequestrants in type 2 diabetes:potential effects on GLP1 secretion[J].Eur J Endocrinol,2014,171(2):R47-R65.DOI:10.1530/EJE-14-0154.
[8]Anderson P D,Mehta N N,Wolfe M L,et al.Innate immunity modulates adipokines in humans[J].J Clin Endocrinol Metab,2007,92(6):2272-2279.DOI:10.1210/jc.2006-2545.
[9]Corrêa-Oliveira R,Fachi J L,Vieira A,et al.Regulation of immune cell function by short-chain fatty acids[J].Clin Transl Immunology,2016,5(4):e73.DOI:10.1038/cti.2016.17.
[10]Canfora E E,Jocken J W,Blaak E E.Short-chain fatty acids in control of body weight and insulin sensitivity[J].Nat Rev Endocrinol,2015,11(10):577-591.DOI:10.1038/nrendo.2015.128.
[11]Shapiro H,Kolodziejczyk A A,Halstuch D,et al.Bile acids in glucose metabolism in health and disease[J].J Exp Med,2018,215(2):383-396.DOI:10.1084/jem.20171965.
[12]Gomes A C,Bueno A A,de Souza R G.Gut microbiota,probiotics and diabetes[J].Nutr J,2014(13):60.DOI:10.1186/1475-2891-13-60.
[13]Samah S,Ramasamy K,Lim S M,et al.Probiotics for the management of type 2 diabetes mellitus:A systematic review and meta-analysis[J].Diabetes Res Clin Prac,2016(118):172-182.DOI:10.1016/j.diabres.2016.06.014.
[14]Sonnenburg J L,Chen C T,Gordon J I.Genomic and metabolic studies of the impact of probiotics on a model gut symbiont and host[J].PLoS Biol,2016,4(12):e413.DOI:10.1371/journal.pbio.0040413.
[15]Jayashree B,Bibin Y S,Prabhu D,et al.Increased circulatory levels of lipopolysaccharide(LPS)and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes[J].Mol Cell Biochem,2014,388(1-2):203-210.DOI:10.1007/s11010-013-1911-4.
[16]Amar J,Chabo C,Waget A,et al.Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes:molecular mechanisms and probiotic treatment[J].EMBO Mol Med,2011,3(9):559-572.DOI:10.1002/emmm.201100159.
[17]Chen P,Zhang Q,Dang H,et al.Oral administration of Lactobacillus rhamnosus CCFM0528 improves glucose tolerance and cytokine secretion in high-fatfed,streptozotocin-induced type 2 diabetic mice[J].JFUNCT FOODS,2014(10):318-326.DOI:10.1016/j.jff.2014.06.014.
[18]LeBlanc J G,Chain F,Martín R,et al.Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria[J].Microb Cell Fact,2017,16(1):79.DOI:10.1186/s12934-017-0691-z.
[19]Angelakis E,Merhej V,Raoult D.Related action of probiotics and antibiotics on gut microbiota and weight modification[J].Lancet Infect Dis,2013,13(10):889-899.DOI:10.1016/S1473-3099(13)70179-8.
[20]Kadooka Y,Sato M,Imaizumi K,et al.Regulation of abdominal adiposity by probiotics(Lactobacillus gasseri SBT2055)in adults with obese tendencies in a randomized controlled trial[J].Eur J Clin Nutr,2010,64(6):636-643.DOI:10.1038/ejcn.2010.19.
[21]Wang L,Zhang J,Guo Z,et al.Effect of oral consumption of probiotic Lactobacillus planatarum P-8 on fecal microbiota,SIgA,SCFAs,and TBAs of adults of different ages[J].Nutrition,2014,30(7-8):776-783.DOI:10.1016/j.nut.2013.11.018.
[22]Kaji I,Karaki S,Tanaka R,et al.Density distribution of free fatty acid receptor 2(FFA2)-expressing and GLP-1-producing enteroendocrine L cells in human and rat lower intestine,and increased cell numbers after ingestion of fructo-oligosaccharide[J].J Mol Histol,2011,42(1):27-38.DOI:10.1007/s10735-010-9304-4.
[23]Balakumar M,Prabhu D,Sathishkumar C,et al.Improvement in glucose tolerance and insulin sensitivity by probiotic strains of Indian gut origin in high-fat diet-fed C57BL/6J mice[J].Eur J Nutr,2018,57(1):279-295.DOI:10.1007/s00394-016-1317-7.
[24]Simon M C,Strassburger K,Nowotny B,et al.Intake of lactobacillus reuteri improves incretin and insulin secretion in glucose-tolerant humans:a proof of concept[J].Diabetes Care,2015,38(10):1827-1834.DOI:10.2337/dc14-2690.
[25]Reis S A,Concei??o L L,Rosa D D,et al.Mechanisms responsible for the hypocholesterolaemic effect of regular consumption of probiotics[J].Nutr Res Rev,2017,30(1):36-49.DOI:10.1017/S0954422416000226.
[26]Pedersen C,Lefevre S,Peters V,et al.Gut hormone release and appetite regulation in healthy non-obese participants following oligofructose intake.A dose-escalation study[J].Appetite,2014(66):44-53.DOI:10.1016/j.appet.2013.02.017.
[27]Ishimwe N,Daliri E B,Lee B H,et al.The perspective on cholesterol-lowering mechanisms of probiotics[J].Mol Nutr Food Res,2015,59(1):94-105.DOI:10.1002/mnfr.201400548.
[28]Kadooka Y,Sato M,Imaizumi K,et al.Regulation of abdominal adiposity by probiotics(Lactobacillus gasseri SBT2055)in adults with obese tendencies in a randomized controlled trial[J].Eur J Clin Nutr,2010,64(6):636-643.DOI:10.1038/ejcn.2010.19.
[29]Kumar A,Ekavali,Chopra K,et al.Current knowledge and pharmacological profile of berberine:An update[J].Eur J Pharmacol,2015(761):288-297.DOI:10.1016/j.ejphar.2015.05.068.
[30]Iwasa K,Moriyasu M,Nader B.Fungicidal and berbicidal activities of berberine related alkaloids[J].Biosci Biotechnol Biochem,2000,64(9):1998-2000.DOI:10 .1271/bbb.64.1998.
[31]崔祥,陶金华,江曙,等.小檗碱与肠道菌群的相互作用研究[J].中国微生态学杂志,2017,29(12):1373-1377.DOI:10.13381/j.cnki.cjm.201712002.
[32]Pan G Y,Wang G J,Liu X D,et al.The involvement of P-glycoprotein in berberine absorption[J].Pharmacol Toxicol,2002,91(4):193-197.
[33]黄兴,李艳芬,寇冠军,等.小檗碱抗动脉粥样硬化作用机制研究进展[J].药物评价研究,2016,39(3):469-473.DOI:10.7501/j.issn.1674-6376.2016.03.029.
[34]Imenshahidi M,Hosseinzadeh H.Berberis vulgaris and berberine:An update review[J].Phytother Res,2016,30(11):1745-1764.DOI:10.1002/ptr.5693.
[35]候丽琼,赵铁耘,张伊祎.黄连素对肥胖胰岛素抵抗大鼠骨骼肌胰岛素抵抗的干预研究[J].四川大学学报(医学版),2015,46(6):827-831.
[36]Lee Y S,Kim W S,Kim K H.Berberine,a natural plant product,activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulinresistant states[J].Diabetes,2006,55(8):2256-2264.DOI:10.2337/db06-0006.
[37]Wang Y,Shou J W,Li X Y,et al.Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism[J].Metabolism,2017(70):72-84.DOI:10.1016/j.metabol.2017.02.003.
[38]Moghaddam H K,Baluchnejadmojarad T,Roghani M.Berberine ameliorate oxidative stress and astrogliosis in the hippocampus of STZ-induced diabetic rats[J].Mol Neurobiol,2014,49(2):820-826.DOI:10.1007/s12035-013-8559-7.
[39]Zhang Y,Limaye P B,Lehman-McKeeman L D,et al.Dysfunction of organic anion transporting polypeptide1a1 alters intestinal bacteria and bile acid metabolism in mice[J].PLoS One,2012,7(4):e34522.DOI:10.1371/journal.pone.0034522.
[40]Memon M A,Khan R N,Riaz S,et al.Methylglyoxal and insulin resistance in berberine-treated type 2 diabetic patients[J].J Res Med Sci,2018(23):110.DOI:10.4103/jrms.JRMS_1078_17.