非酒精性脂肪性肝炎（NASH）瘦患者的肠道微生物群组成与肝损伤相关，且独立于热量摄入：一项前瞻性试点研究。
Gut microbiome composition in lean patients with NASH is associated with liver damage independent of caloric intake: A prospective pilot study.
作者信息
Duarte S M B, Stefano J T, Miele L, Ponziani F R, Souza-Basqueira M, Okada L S R R, de Barros Costa F G, Toda K, Mazo D F C, Sabino E C, Carrilho F J, Gasbarrini A, Oliveira C P
机构信息
Divisao de Gastroenterologia e Hepatologia, Departamento de Gastroenterologia (LIM-07), Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Division of Internal Medicine, Gastroenterology and Hepatology, Area Gastroenterologica, Fondazione Policlinico Universitario Agostino Gemelli Università Cattolica del Sacro Cuore, Rome, Italy.
出版信息
Nutr Metab Cardiovasc Dis. 2018 Apr;28(4):369-384. doi: 10.1016/j.numecd.2017.10.014. Epub 2017 Oct 26.
BACKGROUND AND AIM
The aim of the study was to compare the gut microbiomes from obese and lean patients with or without NASH to outline phenotypic differences.
METHODS AND RESULTS
We performed a cross-sectional pilot study comprising biopsy-proven NASH patients grouped according to BMI. Microbiome DNA was extracted from stool samples, and PCR amplification was performed using primers for the V4 region of the 16S rRNA gene. The amplicons were sequenced using the Ion PGM Torrent platform, and data were analyzed using QIIME software. Macronutrient consumption was analyzed by a 7-day food record. Liver fibrosis ≥ F2 was associated with increased abundance of Lactobacilli (p = 0.0007). NASH patients showed differences in Faecalibacterium, Ruminococcus, Lactobacillus and Bifidobacterium abundance compared with the control group. Lean NASH patients had a 3-fold lower abundance of Faecalibacterium and Ruminococcus (p = 0.004), obese NASH patients were enriched in Lactobacilli (p = 0.002), and overweight NASH patients had reduced Bifidobacterium (p = 0.018). Moreover, lean NASH patients showed a deficiency in Lactobacillus compared with overweight and obese NASH patients. This group also appeared similar to the control group with regard to gut microbiome alpha diversity. Although there were qualitative differences between lean NASH and overweight/obese NASH, they were not statistically significant (p = 0.618). The study limitations included a small sample size, a food questionnaire that collected only qualitative and semi-quantitative data, and variations in group gender composition that may influence differences in FXR signaling, bile acids metabolism and the composition of gut microbiota.
CONCLUSION
Our preliminary finding of a different pathogenetic process in lean NASH patients needs to be confirmed by larger studies, including those with patient populations stratified by sex and dietary habits.
背景与目的
本研究旨在比较患有或未患有非酒精性脂肪性肝炎（NASH）的肥胖和消瘦患者的肠道微生物群，以勾勒出表型差异。
方法与结果
我们进行了一项横断面试点研究，纳入经活检证实的NASH患者，并根据体重指数（BMI）进行分组。从粪便样本中提取微生物群DNA，并使用针对16S rRNA基因V4区域的引物进行PCR扩增。扩增子使用Ion PGM Torrent平台进行测序，数据使用QIIME软件进行分析。通过7天食物记录分析常量营养素的摄入量。肝纤维化≥F2与乳酸杆菌丰度增加相关（p = 0.0007）。与对照组相比，NASH患者在粪杆菌、瘤胃球菌、乳酸杆菌和双歧杆菌的丰度上存在差异。消瘦的NASH患者粪杆菌和瘤胃球菌的丰度低3倍（p = 0.004），肥胖的NASH患者中乳酸杆菌富集（p = 0.002），超重的NASH患者双歧杆菌减少（p = 0.018）。此外，与超重和肥胖的NASH患者相比，消瘦的NASH患者乳酸杆菌缺乏。该组在肠道微生物群α多样性方面也与对照组相似。尽管消瘦的NASH与超重/肥胖的NASH之间存在质的差异，但差异无统计学意义（p = 0.618）。研究局限性包括样本量小、仅收集定性和半定量数据的食物问卷，以及可能影响法尼醇X受体（FXR）信号传导、胆汁酸代谢和肠道微生物群组成差异的组间性别构成差异。
结论
我们关于消瘦的NASH患者存在不同致病过程的初步发现需要通过更大规模的研究来证实，包括按性别和饮食习惯分层的患者群体研究。
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