Intestinal microbiota in patients with nonalcoholic fatty liver disease

Abstract

Despite evidence that the intestinal microbiota (IM) is involved in the pathogenesis of obesity, the IM composition of patients with nonalcoholic fatty liver disease (NAFLD) has not been well characterized. This prospective, cross-sectional study was aimed at identifying differences in IM between adults with biopsy-proven NAFLD (simple steatosis [SS] or nonalcoholic steatohepatitis [NASH]) and living liver donors as healthy controls (HC). Fifty subjects were included: 11 SS, 22 NASH, and 17 HC. One stool sample was collected from each participant. Quantitative real-time polymerase chain reaction was used to measure total bacterial counts, Bacteroides/Prevotella (herein referred to as Bacteroidetes), Clostridium leptum, C. coccoides, bifidobacteria, Escherichia coli and Archaea in stool. Clinical and laboratory data, food records, and activity logs were collected. Patients with NASH had a lower percentage of Bacteroidetes (Bacteroidetes to total bacteria counts) compared to both SS and HC (P 5 0.006) and higher fecal C. coccoides compared to those with SS (P 5 0.04). There were no differences in the remaining microorganisms. As body mass index (BMI) and dietary fat intake differed between the groups (P < 0.05), we performed linear regression adjusting for these variables. The difference in C. coccoides was no longer significant after adjusting for BMI and fat intake. However, there continued to be a significant association between the presence of NASH and lower percentage Bacteroidetes even after adjusting for these variables (P 5 0.002; 95% confidence interval 5 20.06 to 20.02). Conclusion: There is an inverse and diet-/BMI-independent association between the presence of NASH and percentage Bacteroidetes in the stool, suggesting that the IM may play a role in the development of NAFLD. (HEPATOLOGY 2013;58:120-127)

Nonalcoholic Fatty Liver Disease, the Gut Microbiome, and Diet

“…Understanding the functions associated with the microbial community is important, because alterations in the intestinal microbiota have been associated with host diseases, including obesity, type 2 diabetes, and NAFLD (8,21,22). In patients with NAFLD, the microbiome's abundance (23) and community structure is altered (also called dysbiosis) (15,24). The importance of the gut microbiome in the prevention and treatment of NAFLD is highlighted by the fact that fecal transplantation from mice with NAFLD into wild-type mice caused NAFLD in mice that received the microbiota (25).…”

“…Thus, the dysbiosis may be related to these metabolic disturbances, considering that several studies suggested that increased Firmicutes and reduced Bacteroidetes may be a cause of obesity (17,47). However, the reduction in Bacteroidetes is not simply a cause of obesity in patients with NASH, considering that Bacteroidetes abundance is reduced in these patients even after adjusting for BMI and fat intake (24).…”

Predictive roles of gut dysbiosis on the severity of nonalcoholic fatty liver disease

“…As one of the microbiota-driven diseases, NAFLD could not just alter those abundant bacteria. (4) In addition, the sensitivity and specificity of the microbiota-targeted biomarkers should be provided in order to facilitate the clinical application for NAFLD noninvasive discrimination. Receiver-operating characteristic curves could be used to identify the best cutoff levels for these bacteria, while the respective areas under the curve could represent the diagnostic accuracy for NAFLD.…”

“…Furthermore, they found substantially higher VEGF levels compared to our previous reports. (4) In this context, we would like to stress that plasma preparation is prone to artifacts as platelets are highly sensitive to in vitro activation. (4) Therefore, it is mandatory to use the citrate, theophylline, adenosine, and dipyridamole mixture as an anticoagulant for plasma preparation and to process samples within 30 minutes at 48C to determine platelet-derived VEGF.…”

“…(4) In this context, we would like to stress that plasma preparation is prone to artifacts as platelets are highly sensitive to in vitro activation. (4) Therefore, it is mandatory to use the citrate, theophylline, adenosine, and dipyridamole mixture as an anticoagulant for plasma preparation and to process samples within 30 minutes at 48C to determine platelet-derived VEGF. These technical aspects, as well as the limited number of patients, might partly explain the discrepancy between the results obtained by Lisman and Porte and our observations.…”