补充维生素D对非酒精性脂肪肝病患者肠道菌群的影响

Effects of Vitamin D Supplement on Gut Microbiota in Nonalcoholic Fatty Liver Disease Patients

为探索补充维生素D(VD)对于NAFLD患者肠道菌群的影响。本研究共纳入29例NAFLD患者,采用随机分组法分为对照组(只接受内科治疗,n=15)和VD组(在内科治疗的基础上,补充维生素D_(2),n=14)。根据中国药典的剂量标准,对VD组NAFLD患者一次性给予60万国际单位VD_(2),肌肉注射。30天后测定患者血清生化指标,采集患者粪便,进行16S r RNA测序分析,比较治疗前后肠道菌群在多样性、丰度的变化,以及肠道菌群与生化指标的相关性。研究结果表明:补充VD之后,NAFLD患者血清丙氨酸氨基转移酶(ALT)水平显著降低(P<0.001),肠道菌群多样性无显著变化(P>0.05),但毛螺菌科丰度显著降低(P<0.01),丹毒丝菌科(P<0.01)、丹毒丝菌科未命名属(P<0.05)丰度显著升高;毛螺菌科相对丰度水平与血清甘油三酯(TG)(P<0.05)呈显著正相关,丹毒丝菌科(P<0.01)和丹毒丝菌科未命名属(P<0.05)与血清25(OH)D水平呈显著正相关,而与ALT、天门冬氨酸氨基转移酶(AST)呈显著负相关(ALT:P<0.000 1;AST:P<0.05);补充VD能够显著降低血清ALT水平,对NAFLD患者肝损伤有一定改善作用;VD能显著降低患者肠道菌群毛螺菌科的丰度,显著提高丹毒丝菌科和丹毒丝菌科未命名属的丰度,进而降低血清TG、ALT和AST水平。

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 VD_(2) treatment.According to Chinese Pharmacopoeia,NAFLD patients were given 600 000 IU VD_(2) 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 r RNA sequencing analysis.The diversity and abundance of microbiota before and after the VD_(2) 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<0.0001,AST:P<0.05).In conclusion,VD supplement can reduce the serum ALT significantly,and alleviate the liver injury of NAFLD patients.VD can significantly reduce the abundance of Lachnospiraceae,significantly increase the abundance of Erysipelotrichaceae,unidentified_Erysipelotrichaceae,then decrease serum TG,serum ALT and serum AST.