This study aimed to determine if there is an association between dysbiosis and nonalcoholic fatty liver disease (NAFLD) independent of obesity and insulin resistance (IR). This is a prospective cross-sectional study assessing the intestinal microbiome (IM) of 39 adults with biopsy-proven NAFLD (15 simple steatosis [SS]; 24 nonalcoholic steatohepatitis [NASH]) and 28 healthy controls (HC). IM composition (llumina MiSeq Platform) in NAFLD patients compared to HC were identified by two statistical methods (Metastats, Wilcoxon). Selected taxa was validated using quantitative PCR (qPCR). Metabolites in feces and serum were also analyzed. In NAFLD, 8 operational taxonomic units, 6 genera, 6 families and 2 phyla (Bacteroidetes, Firmicutes) were less abundant and; 1 genus (Lactobacillus) and 1 family (Lactobacillaceae) were more abundant compared to HC. Lower abundance in both NASH and SS patients compared to HC were confirmed by qPCR for Ruminococcus, Faecalibacterium prausnitzii and Coprococcus. No difference was found between NASH and SS. This lower abundance in NAFLD (NASH+SS) was independent of BMI and IR. NAFLD patients had higher concentrations of fecal propionate and isobutyric acid and serum 2-hydroxybutyrate and L-lactic acid. These findings suggest a potential role for a specific IM community and functional profile in the pathogenesis of NAFLD.

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Several mechanisms contribute to the pathogenesis of non‑alcoholic fatty liver disease (NAFLD). The intestinal microbiota (IM) and liver immune cells (LIC) may serve a role, but there has been no previous study assessing potential associations between IM and LIC. The aim of the present study was to investigate whether there are differences in LIC markers between patients with NAFLD and healthy controls (HC), and to determine whether these markers are associated with specific IM. The present prospective, cross‑sectional study examined a cohort of adults with liver biopsy‑confirmed NAFLD and HC. Clinical and laboratory data were collected. Fecal IM was assessed by quantitative polymerase chain reaction and LIC, by immunohistochemistry. NAFLD activity score (NAS) was used for disease severity. Liver immune cell counts were increased in patients with NAFLD (n=34) vs. HC (n=8) and this was associated with disease severity. Hematopoietic cell marker cluster of differentiation (CD)45+ and Kupffer cell marker CD163+ were higher in NAFLD compared with HC, and those with an NAS ≥5 had higher levels of CD20+ cells, a marker of B cells, vs. a NAS of 0 or 1‑4. Additionally, from those patients (5 HC, 34 NAFLD), IM was measured. Specific immune cells in portal or lobular areas correlated with specific fecal IM, suggesting a potential association between IM and liver inflammation in patients with NAFLD. Specifically, Faecalibacterium prausnitzii was negatively correlated with CD45+ (r= ‑0.394; P=0.015) and CD163+ (r= ‑0.371; P=0.022) cells in the portal tract and Prevotella was negatively correlated with CD20+ (r= ‑0.353; P=0.028) cells in the liver lobule. Other taxa exhibited no correlation. In conclusion, the present study demonstrated a potential association between IM and liver inflammation in NAFLD.