Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul, Republic of Korea.
Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
PLoS One. 2019 Mar 14;14(3):e0213692. doi: 10.1371/journal.pone.0213692. eCollection 2019.
Pathophysiological background in different phenotypes of nonalcoholic fatty liver disease (NAFLD) remains to be elucidated. The aim was to investigate the association between fecal and blood microbiota profiles and the presence of NAFLD in obese versus lean subjects. Demographic and clinical data were reviewed in 268 health checkup examinees, whose fecal and blood samples were available for microbiota analysis. NAFLD was diagnosed with ultrasonography, and subjects with NAFLD were further categorized as obese (body mass index (BMI) ≥25) or lean (BMI <25). Fecal and blood microbiota communities were analyzed by sequencing of the V3-V4 domains of the 16S rRNA genes. Correlation between microbiota taxa and NAFLD was assessed using zero-inflated Gaussian mixture models, with adjustment of age, sex, and BMI, and Bonferroni correction. The NAFLD group (n = 76) showed a distinct bacterial community with a lower biodiversity and a far distant phylotype compared with the control group (n = 192). In the gut microbiota, the decrease in Desulfovibrionaceae was associated with NAFLD in the lean NAFLD group (log2 coefficient (coeff.) = -2.107, P = 1.60E-18), but not in the obese NAFLD group (log2 coeff. = 1.440, P = 1.36E-04). In the blood microbiota, Succinivibrionaceae showed opposite correlations in the lean (log2 coeff. = -1.349, P = 5.34E-06) and obese NAFLD groups (log2 coeff. = 2.215, P = 0.003). Notably, Leuconostocaceae was associated with the obese NAFLD in the gut (log2 coeff. = -1.168, P = 0.041) and blood (log2 coeff. = -2.250, P = 1.28E-10). In conclusion, fecal and blood microbiota profiles showed different patterns between subjects with obese and lean NAFLD, which might be potential biomarkers to discriminate diverse phenotypes of NAFLD.
非酒精性脂肪性肝病(NAFLD)的不同表型的病理生理背景仍有待阐明。本研究旨在探讨肥胖与非肥胖个体粪便和血液微生物群特征与 NAFLD 之间的关系。对 268 名健康体检者的人口统计学和临床数据进行了回顾性分析,这些个体的粪便和血液样本均可用于微生物组分析。NAFLD 通过超声诊断,NAFLD 患者进一步分为肥胖(BMI≥25)或非肥胖(BMI<25)。通过 16S rRNA 基因 V3-V4 区域的测序分析粪便和血液微生物群落。使用零膨胀高斯混合模型评估微生物群与 NAFLD 之间的相关性,调整年龄、性别和 BMI,并进行 Bonferroni 校正。与对照组(n=192)相比,NAFLD 组(n=76)的细菌群落具有明显的特征,其生物多样性较低,且与其他组的细菌种类差异较大。在肠道微生物群中,脱硫弧菌科的减少与瘦型非肥胖性脂肪肝患者的 NAFLD 相关(log2 系数(coeff.)=-2.107,P=1.60E-18),但与肥胖型非肥胖性脂肪肝患者无关(log2 coeff. = 1.440,P=1.36E-04)。在血液微生物群中,琥珀酸弧菌科在瘦型(log2 coeff. = -1.349,P=5.34E-06)和肥胖型非肥胖性脂肪肝患者中呈现相反的相关性(log2 coeff. = 2.215,P=0.003)。值得注意的是,肠内 Leuconostocaceae 与肥胖型非肥胖性脂肪肝有关(log2 coeff. = -1.168,P=0.041),血液中也存在相关性(log2 coeff. = -2.250,P=1.28E-10)。总之,肥胖和非肥胖性 NAFLD 患者的粪便和血液微生物群特征存在不同模式,这可能是鉴别 NAFLD 不同表型的潜在生物标志物。