Abstract
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.