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

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.

Emerging Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease: From Composition to Function

“…However, studies have demonstrated contradictory findings in the relative abundance of Ruminococcus , Prevotella , and Bifidobacterium . Only one study has evaluated the gut microbiota in non-obese adults and found a decrease in Lactobacillus 15 , contrary to findings in obese NAFL.…”

“…In NAFL, comparison groups included healthy controls 9,8,10,11,15,16,18,23 and obese controls 21 . In NASH, comparison groups included healthy controls 9,10,12,13,18,19 , obese controls 7 , and NAFL 24,16 .…”

“…In NAFLD-associated advanced fibrosis, comparison groups included healthy controls 20 and NAFLD without advanced fibrosis (stage<2) 17,24,22,16 . In NAFLD-related HCC, the comparison group included NAFLD-related cirrhosis without HCC 20 . + The fecal and serum metabolites listed are postulated to be derived from the gut microbiome. ± Two studies enrolled only non-obese subjects, in order to examine compositional changes in non-obese (“lean”) NAFL 15 and NASH 19 . Abbreviations : nonalcoholic fatty liver disease (NAFLD), nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC). …”

Sex-dependent effects on gut microbiota regulate hepatic carcinogenic outcomes

“…It has been reported that fecal samples from colon cancer patients had less bacterial diversity compared with samples from healthy individuals and a lower amount of bacterial diversity in the gut may indicate a lack of balance in the complex bacterial population30. Findings also showed that the non-obese patients with nonalcoholic fatty liver disease were characterized by a decrease in gut microbial diversity31. As shown in our data, a significant decrease in the Simpson index (alpha diversity) was only observed in STZ-HFD male mice relative to controls (Supplementary Table S1), which may be a reason why the male mice had a higher risk of developing HCC relative to females.…”

The role of bile acids in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

“…Adipose tissue releases cytokines to increase inflammation and fibrosis. Gut microbiota is also believed to play a role in the development of NASH via alterations in the BA pool level and composition (Jiang et al, 2015; Liu et al, 2016b; Mei et al, 2015; Wang et al, 2016). Recently, vitamin D deficiency has been proposed as another possible factor as mice fed a high fat diet (HFD) exhibited increased steatosis and hepatic ballooning when coupled with a vitamin D deficiency (Kong et al, 2014).…”