Journal of South China University of Technology(Natural Science) >
Effects of Vitamin D Supplement on Gut Microbiota in Nonalcoholic Fatty Liver Disease Patients
Received date: 2021-11-12
Online published: 2022-02-08
Supported by
the Science and Technology Program of Sichuan Province(20ZDYF0122)
To explore the effect of VD supplement on the gut microbiota of NAFLD patients, this paper carried out a controlled clinical research on 29 NAFLD patients who were randomly divided into control group (n=15) who received the standard care and internal medical treatment, and VD treatment group (n=14) who received the standard care and internal medical treatment plus high dose of VD2 treatment. According to Chinese Pharmacopoeia, NAFLD patients were given 600 000 IU VD2 by intramuscular injection at once. At day 30, serum biochemistry indicators were determined, stool samples were collected, and the fecal microbiota was measured by 16S rRNA sequencing analysis. The diversity and abundance of microbiota before and after the VD2 treatment were compared and the correlation between microbiota and biochemistry indicators was detected. The results show that after VD supplement, the serum alanine aminotransferase (ALT) of NAFLD patients is significantly decreased（P<0.001）, and there is no significant change in the gut microbiota diversity. However, there is a significant decrease in family Lachnospiraceae (P<0.01), a significant increase in family Erysipelotrichaceae (P <0.01) and genus unidentified_Erysipelotrichaceae (P<0.05) after VD supplement; the relative abundance of family Lachnospiraceae was significantly positively correlated with serum triglycerides (TG) levels (P<0.05); the relative abundance of family Erysipelotrichaceae (P<0.01) and genus unidentified_Erysipelotrichaceae (P<0.05) were significantly positively correlated with 25(OH)D, negatively correlated with serum ALT, serum aspartate aminotransferase (AST) (ALT: P<0.000 1, AST: P<0.05). In conclusion, VD supplement can reduce the serum ALT significantly, and alleviate the liver injury of NAFLD patients. VDcan significantly reduce the abundance of Lachnospiraceae, significantly increase the abundance of Erysipelotrichaceae, unidentified_Erysipelotrichaceae, then decrease serum TG, serum ALT and serum AST.
Key words： nonalcoholic fatty liver disease; vitamin D; gut microbiota; serum TG; serum ALT; serum AST
HAN Yuanping, XU Siya, JIAN Xile . Effects of Vitamin D Supplement on Gut Microbiota in Nonalcoholic Fatty Liver Disease Patients[J]. Journal of South China University of Technology(Natural Science), 2022 , 50(11) : 62 -73 . DOI: 10.12141/j.issn.1000-565X.210715
| 1 | FRIEDMAN S L， NEUSCHWANDER-TETRI B A， RINELLA M，et al ．Mechanisms of NAFLD development and therapeutic strategies ［J］．Nature Medicine，2018，24（7）：908-922. |
| 2 | VERNON G， BARANOVA A， YOUNOSSI Z M ．Systematic review：the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults ［J］．Alimentary Pharmacology and Therapeutics，2011，34（3）：274-285. |
| 3 | YOUNOSSI Z M， KOENIG A B， ABDELATIF D，et al ．Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence，incidence，and outcomes ［J］．Hepatology，2016，64（1）：73-84. |
| 4 | ZHOU J， ZHOU F， WANG W，et al ．Epidemiological features of NAFLD From 1999 to 2018 in China ［J］．Hepatology，2020，71（5）：1851-1864. |
| 5 | ESTES C， ANSTEE Q M， ARIAS-LOSTE M，et al ．Modeling NAFLD disease burden in China，France，Germany，Italy，Japan，Spain，United Kingdom，and United States for the period 2016—2030 ［J］．Journal of Hepatology，2018，69（4）：896-904. |
| 6 | POLYZOS S A， KOUNTOURAS J， MANTZOROS C S ．Obesity and nonalcoholic fatty liver disease：from pathophysiology to therapeutics ［J］．Metabolism，2019，92：82-97. |
| 7 | ISSA D， PATEL V， SANYAL A J ．Future therapy for non-alcoholic fatty liver disease ［J］．Liver International，2018，38（S1）：56-63. |
| 8 | DAY C P， JAMES O F W ．Steatohepatitis：a tale of two "hits"？［J］．Gastroenterology，1998，114（4）：842-845. |
| 9 | TILG H， MOSCHEN A R ．Evolution of inflammation in nonalcoholic fatty liver disease：the multiple parallel hits hypothesis ［J］．Hepatology，2010，52（5）：1836-1846. |
| 10 | CHASSAING B， ETIENNE-MESMIN L， GEWIRTZ A T ．Microbiota-liver axis in hepatic disease ［J］．Hepatology，2014，59（1）：328-339. |
| 11 | PENDYALA S， WALKER J M， HOLT P R ．A high-fat diet is associated with endotoxemia that originates from the gut ［J］．Gastroenterology，2012，142（5）：1100-1101. |
| 12 | HENAO-MEJIA J， ELINAV E， STROWIG T，et al ．Inflammasomes：far beyond inflammation ［J］．Nature Immunology，2012，13（4）：321-324. |
| 13 | SHEN F， ZHENG Rui-Dan， SUN Xing-Qiang，et al ．Gut microbiota dysbiosis in patients with non-alcoholic fatty liver disease ［J］．Hepatobiliary & Pancreatic Diseases International，2017，16（4）：375-381. |
| 14 | SCHWIMMER J B， JOHNSON J S， ANGELES J E，et al ．Microbiome signatures associated with steatohepatitis and moderate to severe fibrosis in children with nonalcoholic fatty liver disease ［J］．Gastroenterology，2019，157（4）：1109-1122. |
| 15 | ZHU L， BAKER S S， GILL C，et al ．Characterization of gut microbiomes in nonalcoholic steatohepatitis （NASH） patients：a connection between endogenous alcohol and NASH ［J］．Hepatology，2013，57（2）：601-609. |
| 16 | PARK D， KWON H， OH S W，et al ．Is vitamin D an independent risk factor of nonalcoholic fatty liver disease？：a cross-sectional study of the healthy population ［J］．Journal of Korean Medical Science，2017，32（1）：95-101. |
| 17 | KIM H S， ROTUNDO L， KOTHARI N，et al ．Vitamin D is associated with severity and mortality of non-alcoholic fatty liver disease：a US population-based study ［J］．Journal of Clinical and Translational Hepatology，2017，5（3）：185-192. |
| 18 | TARGHER G， BERTOLINI L， SCALA L，et al ．Associations between serum 25-hydroxyvitamin D3 concentrations and liver histology in patients with non-alcoholic fatty liver disease ［J］．Nutrition，Metabolism and Cardiovascular Diseases，2007，17（7）：517-524. |
| 19 | ELIADES M， SPYROU E， AGRAWAL N，et al ．Meta-analysis：vitamin D and non-alcoholic fatty liver disease ［J］．Alimentary Pharmacology & Therapeutics，2013，38（3）：246-254. |
| 20 | SU D， NIE Y， ZHU A，et al ．Vitamin D signaling through induction of paneth cell defensins maintains gut microbiota and improves metabolic disorders and hepatic steatosis in animal models ［J］．Frontiers in Physiology，2016，7：498. |
| 21 | LUTHOLD R V， FERNANDES G R， FRANCO-DE-MORAES A C，et al ．Gut microbiota interactions with the immunomodulatory role of vitamin D in normal individuals ［J］．Metabolism，2017，69：76-86. |
| 22 | KANHERE M， HE J， CHASSAING B，et al ．Bolus weekly vitamin D3 supplementation impacts gut and airway microbiota in adults with cystic fibrosis：a double-blind，randomized，placebo-controlled clinical trial ［J］．The Journal of Clinical Endocrinology & Metabolism，2018，103（2）：564-574. |
| 23 | GHALY S， KAAKOUSH N O， LLOYD F，et al ．High dose vitamin D supplementation alters faecal microbiome and predisposes mice to more severe colitis ［J］．Scientific Reports，2018，8（1）：11511. |
| 24 | WATERHOUSE M， HOPE B， KRAUSE L，et al ．Vitamin D and the gut microbiome：a systematic review of in vivo studies ［J］．European Journal of Nutrition，2019，58（7）：2895-2910. |
| 25 | YUE S， ZHAO D， PENG C，et al ．Effects of theabrownin on serum metabolites and gut microbiome in rats with a high-sugar diet ［J］．Food & Function，2019，10（11）：7063-7080. |
| 26 | 廖祥鹏，张增利，张红红，等，维生素D与成年人骨骼健康应用指南（2014年标准版） ［J］．中国骨质疏松杂志，2014，20（9）：1011-1030. |
| 26 | LIAO Xiang-peng， ZHANG Zeng-li， ZHANG Hong-hong，et al ．Application guideline for vitamin D and bone health in adult Chinese （ 2014 standard edition） ［J］．Chinese Journal of Osteoporosis，2014，20（9）：1011-1030. |
| 27 | YU S， FANG H， HAN J，et al ．The high prevalence of hypovitaminosis D in China：a multicenter vitamin D status survey ［J］．Medicine，2015，94（8）：e585/1-6. |
| 28 | 程义勇 ．《中国居民膳食营养素参考摄入量》2013修订版简介 ［J］．营养学报，2014，36（4）：313-317. |
| 28 | CHENG Yi-yong，Introduction to the Chinese Dietary Reference Intakes （2013 Revised Edition） ［J］．Acta Nutrimenta Sinica，2014，36（4）：313-317. |
| 29 | HOLICK M F， BINKLEY N C， BISCHOFF-FERRARI H A，et al ．Evaluation，treatment，and prevention of vitamin D deficiency：an endocrine society clinical practice guideline ［J］．The Journal of Clinical Endocrinology and Metabolism，2011，96（7）：1911-1930. |
| 30 | AMIRI H L， AGAH S， AZAR J T，et al ．Effect of daily calcitriol supplementation with and without calcium on disease regression in non-alcoholic fatty liver patients following an energy-restricted diet：randomized，controlled，double-blind trial ［J］．Clinical Nutrition，2017，36（6）：1490-1497. |
| 31 | SHARIFI N， AMANI R， HAJIANI E，et al ．Does vitamin D improve liver enzymes，oxidative stress，and inflammatory biomarkers in adults with non-alcoholic fatty liver disease？a randomized clinical trial ［J］．Endocrine，2014，47（1）：70-80. |
| 32 | 曾义岚，韩源平，王丽，等，维生素D缺乏与非酒精性脂肪性肝病的关系及机制 ［J］．中国肝脏病杂志（电子版），2019，11（1）：12-16. |
| 32 | ZENG Yi-lan， HAN Yuan-ping， WANG Li，et al ．Relationship between vitamin D deficiency and non-alcoholic fatty liver disease and its mechanism ［J］．Chinese Journal of Liver Diseases （Electronic Version），2019，11（1）：12-16. |
| 33 | ZENG Y， LUO M， PAN L，et al ．Vitamin D signaling maintains intestinal innate immunity and gut microbiota：potential intervention for metabolic syndrome and NAFLD ［J］．American Journal of Physiology-Gastrointestinal and Liver Physiology，2020，318（3）：G542-G553. |
| 34 | KAMEYAMA K， ITOH K，Intestinal colonization by a Lachnospiraceae bacterium contributes to the development of diabetes in obese mice ［J］．Microbes and Environments，2014，29（4）：427-430. |
| 35 | ZENG H， ISHAQ S L， ZHAO F Q，et al ．Colonic inflammation accompanies an increase of beta-catenin signaling and Lachnospiraceae/Streptococcaceae bacteria in the hind gut of high-fat diet-fed mice ［J］．The Journal of Nutritional Biochemistry，2016，35：30-36. |
| 36 | KISHIDA Y， OKUBO H， OHNO H，et al ．Effect of miglitol on the suppression of nonalcoholic steatohepatitis development and improvement of the gut environment in a rodent model ［J］．Journal of Gastroenterology，2017，52（11）：1180-1191. |
| 37 | CAVALLARI J F， POKRAJAC N T， ZLITNI S，et al ．NOD2 in hepatocytes engages a liver-gut axis to protect against steatosis，fibrosis，and gut dysbiosis during fatty liver disease in mice ［J］．American Journal of Physiology. Endocrinology and Metabolism，2020，319（2）：E305-E314. |
| 38 | BOSMAN E S， ALBERT A Y，LUI H，et al ．Skin exposure to narrow band ultraviolet （UVB） light modulates the human intestinal microbiome ［J］．Frontiers in Microbiology，2019，10：2410. |
/
| 〈 |
|
〉 |