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. 2016 Aug 23:6:32002.
doi: 10.1038/srep32002.

Altered Fecal Microbiota Correlates with Liver Biochemistry in Nonobese Patients with Non-alcoholic Fatty Liver Disease

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Altered Fecal Microbiota Correlates with Liver Biochemistry in Nonobese Patients with Non-alcoholic Fatty Liver Disease

Baohong Wang et al. Sci Rep. .

Abstract

Increasing evidence suggests a role of intestinal dysbiosis in obesity and non-alcoholic fatty liver disease (NAFLD). But it remains unknown in nonobese NAFLD. This prospective, cross-sectional study sought to characterize differences in fecal microbiota between nonobese adult individuals with and without NAFLD and their potential association with metabolic markers of disease progression. A total of 126 nonobese subjects were enrolled: 43 NAFLD and 83 healthy controls (HC). The microbial community was profiled by denaturing gradient gel electrophoresis and examined by 454 pyrosequencing of the 16S ribosomal RNA V3 region. Lower diversity and a phylum-level change in the fecal microbiome were found in NAFLD. Compared with HC, patients had 20% more phylum Bacteroidetes (p = 0.005) and 24% less Firmicutes (p = 0.002). Within Firmicutes, four families and their 8 genera, which were short-chain fatty acids-producing and 7α-dehydroxylating bacteria, were significantly decreased. Moreover, Gram-negative (G-) bacteria were prevalent in NAFLD (p = 0.008). Furthermore, a significant correlation with metabolic markers was revealed for disturbed microbiota in NAFLD. This novel study indicated that intestinal dysbiosis was associated with nonobese NAFLD and might increase the risk of NAFLD progression.

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Figures

Figure 1
Figure 1. PLS-DA score plots based on DGGE profiles distinguishing between the fecal microbial communities in nonobese individuals with and without NAFLD.
(A) NAFLD patients vs. HCs, (B) ND vs. HCs, (C) NS vs. HCs, and (D) ND vs. NS. HCs (n = 55), healthy controls; ND (n = 20), individuals with NAFLD; NS (n = 14), NAFLD patients with elevated serum liver enzymes.
Figure 2
Figure 2. The 454 pyrosequencing analysis revealing decreased ecological diversity of the fecal microbiome in nonobese individuals with NAFLD patients (n = 10) compared with individuals without NAFLD (n = 15).
(A) The Shannon diversity index, (B) the Simpson diversity index, and (C) the rarefaction curve trend between patients with NAFLDs and HCs; (D) PLS-DA score plots based on the relative abundances of microbial genera of the first two components (t [1] = 20.9%, t [2] = 16.1%) showed the trend that the two groups were well separated.
Figure 3
Figure 3. The relative abundances of fecal microbiota significantly differed in individuals with and without NAFLD in the nonobese cohort.
(A) Ratios of the phyla Firmicutes and Bacteroidetes, (B) phyla Firmicutes and Bacteroidetes, (C) classes clostridia and Bacteroidia, (D) families Lachnospiraceae and Ruminococcaceae; (E) Lactobacillaceae and Peptostreptococcaceae; (F) G+ and G− bacteria; (G) The ratios of G− to G+ bacteria.
Figure 4
Figure 4

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