Study on the characteristics of gut microbiota in diabetes with metabolic associated fatty liver disease

doi:10.19871/j.cnki.xfcrbzz.2023.02.001

Abstract

Abstract: Objective To explore the correlation between the occurrence and development of metabolic associated fatty liver disease (MAFLD) in diabetes and fat metabolism related genes and gut microbiota, and to provides a new idea for the prevention and treatment of diabetes combined with MAFLD. Method 21 Mice were randomly divided into diabetes group(6 cases) and diabetes with MAFLD group(15 cases). The mice in the diabetes group and the mice in the diabetes combined with MAFLD group were fed with high sugar and high fat diet for 35 days and 63 days respectively, then the levels of blood glucose, blood lipids, liver function, insulin, liver lipoprotein lipase (LPl), fatty acid synthase (Fasn) and intestinal flora in the two groups were detected, and the changes of liver HE staining and intestinal tight junction protein in diabetes with MAFLD group were observed. Fifteen diabetes patients hospitalized in the Sixth People's Hospital of Shenyang from November 2021 to June 2022 were divided into diabetes group (7 cases) and diabetes with MAFLD group (8 cases). Whole genome shotgun sequencing was used to detect the gut microbiota in feces samples of patients. Result Compared with the diabetes group, the levels of blood lipid, liver function and insulin in diabetes with MAFLD group were lower, while the levels of blood glucose, liver LPl and Fasn were higher. The HDL-C, LPl and Fasn had significant difference between the two groups (P<0.05). The changes in liver HE staining and intestinal tight junction protein were observed between 4 weeks before and 2 weeks after successful modeling in both groups of mice, with the progress of MAFLD, liver cells first appeared lipid accumulation, then developed into ballooning degeneration, and the expression levels of intestinal tight junction protein presented a gradual downward trend. Compared with the diabetes group, the Ruminococcus abundance in diabetes with MAFLD group was higher in both mice and patients, the difference was statistically significant (P<0.05). Compared with non obesity patients, the abundance of Ruminococcus, Blautia and Collinsella in obesity patients were increased, while the abundance of Bifidobacteria was decreased, the differences between the two groups were statistically significant(P<0.05). Conclusion In the development of diabetes combined with MAFLD, lipid deposition in the liver occurs before the changes of intestinal tight junction protein. Ruminococcus and high expression of LPl and Fasn in the liver may play an important role in the occurrence of MAFLD. Ruminococcus, Blautia and Collinsella may related to obesity, while Bifidobacterium has a protective effect on obesity.

Key words: Diabetes, Metabolic associated fatty liver disease, Gut microbiota, Obesity

CLC Number:

R587.1

Liu Xing, Wang Xiaomei, Gu Ye, Guan Xin, Zhang Zhen, Li Xinyue, Li Meiyuxi, Li Lizhu, Wang Yan. Study on the characteristics of gut microbiota in diabetes with metabolic associated fatty liver disease[J]. Electronic Journal of Emerging Infectious Diseases, 2023, 8(2): 1-7.

References

[1] VERNON G, BARANOVA A, YOUNOSSI ZM, et al.Systematic review: The epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults[J]. Aliment Pharmacol Ther, 2011, 34(3): 274-285.
[2] 李玉丹, 董常峰, 刘映霞,等. VTQ与APRI诊断慢性乙型病毒性肝炎合并非酒精性脂肪肝肝纤维化的价值[J/CD]. 新发传染病电子杂志, 2017, 2(2):68-71,75.
[3] WU D, LIU Z, WANG Y, et al.Epigallocatechin-3-Gallate Alleviates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease via Inhibition of Apoptosis and Promotion of Autophagy through the ROS/MAPK Signaling Pathway[J]. Oxid Med Cell Longev, 2021, 2021:5599997.
[4] 薛芮, 范建高. 代谢相关脂肪性肝病新定义的国际专家共识简介[J]. 临床肝胆病杂志, 2020, 36(6): 1224-1227.
[5] 范建高,曾静.非酒精性脂肪性肝病的流行现状与危害[J]. 中华消化杂志, 2020, 40(9): 577-580.
[6] MILOSEVIC I, VUJOVIC A, BARAC A, et al.Gut-Liver Axis, Gut Microbiota, and Its Modulation in the Management of Liver Diseases: A Review of the Literature[J]. Int J Mol Sci, 2019, 20(2): 395.
[7] TSAI HJ, TSAI YC, HUNG WW, et al.Gut Microbiota and Non-Alcoholic Fatty Liver Disease Severity in Type 2 Diabetes Patients[J]. J Pers Med, 2021, 11(3):238.
[8] 彭晓玲. 糖尿病合并MAFLD的临床特征及相关因素分析[D].大理:大理大学, 2022.
[9] TARGHER G, LONARDO A, BYRNE CD.Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus[J]. Nat Rev Endocrinol, 2018, 14(2):99-114.
[10] IRUZUBIETA P, MEDINA JM, FERNANDEZ-LOPEZ R, et al.A Role for Gut Microbiome Fermentative Pathways in Fatty Liver Disease Progression[J]. J Clin Med, 2020, 9(5): 1369-1373.
[11] ABU-SHANAB A, QUIGLEY EM.The role of the gut microbiota in nonalcoholic fatty liver disease[J]. Nat Rev Gastroenterol Hepatol, 2010, 7(12): 691-701.
[12] ALLIN KH, NIELSEN T, PEDERSEN O.Mechanisms in endocrinology: Gut microbiota in patients with type 2 diabetes mellitus[J]. Eur J Endocrinol, 2015, 172(4): 167-177.
[13] TAI N, WONG FS, WEN L, et al.The role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity[J]. Rev Endocr Metab Disord, 2015, 16(1): 55-65.
[14] KERSTEN S.Physiological regulation of lipoprotein lipase[J]. Biochim Biophys Acta, 2014, 1841(7): 919-933.
[15] CHEN X, HUANG K, HU S, et al.FASN-Mediated Lipid Metabolism Regulates Goose Granulosa Cells Apoptosis and Steroidogenesis[J]. Front Physiol, 2020, 11: 600.
[16] 田丽艳, 范建高, 钱燕, 等. 链脲佐菌素糖尿病大鼠的肝脏损伤[J]. 肝脏, 2005, 10(2): 135-136.
[17] 谢璐蔓,黄葵,覃善芳.381例艾滋病患者肠道感染情况及耐药性分析[J/CD].新发传染病电子杂志,2021,6(3):220-224.
[18] DIAMANT M, BLAAK EE, DE VOS WM.Do nutrient-gut-microbiota interactions play a role in human obesity, insulin resistance and type 2 diabetes?[J]. Obes Rev, 2011, 12: 272-281
[19] LOOMBA R, SEGURITAN V, LI W, et al. Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease[J]. Cell Metab, 2017, 25(5): 1054-1062.e5.
[20] GRABHERR F, GRANDER C, EFFENBERGER M, et al.Gut Dysfunction and Non-alcoholic Fatty Liver Disease[J]. Front Endocrinol (Lausanne), 2019, 10:611.
[21] BOURSIER J, MUELLER O, BARRET M, et al.The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota[J]. Hepatology, 2016, 63(3):764-775.
[22] WANG B, JIANG X, CAO M, et al.Altered Fecal Microbiota Correlates with Liver Biochemistry in Nonobese Patients with Non-alcoholic Fatty Liver Disease[J]. Sci Rep, 2016, 6: 32002.
[23] SINHA SR, HAILESELASSIE Y, NGUYEN LP, et al. Dysbiosis-Induced Secondary Bile Acid Deficiency Promotes Intestinal Inflammation[J]. Cell Host Microbe, 2020, 27(4):659-670.e5.
[24] GOFFREDO M, MASS K, PARKS EJ, et al.Role of Gut Microbiota and Short Chain Fatty Acids in Modulating Energy Harvest and Fat Partitioning in Youth[J]. J Clin Endocrinol Metab, 2016,101(11): 4367-4376.
[25] TANG W, YAO X, XIA F, et al.Modulation of the Gut Microbiota in Rats by Hugan Qingzhi Tablets during the Treatment of High-Fat-Diet-Induced Nonalcoholic Fatty Liver Disease[J]. Oxid Med Cell Longev, 2018, 2018: 7261619.
[26] ZHANG X, SHEN D, FANG Z, et al.Human gut microbiota changes reveal the progression of glucose intolerance[J]. PLoS One, 2013, 8(8):e71108.
[27] RUIZ-LIMÓN P, MENA-VÁZQUEZ N, MORENO-INDIAS I, et al. Collinsella is associated with cumulative inflammatory burden in an established rheumatoid arthritis cohort[J]. Biomed Pharmacother, 2022, 153:113518.