Predictive roles of gut dysbiosis on the severity of nonalcoholic fatty liver disease
Authors: Zongxin Ling, Xia Liu, Yiwen Cheng, Lanjuan Li
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. To the Editor: We read with great interest the recent work of Boursier et al., who investigated the relationship between gut dysbiosis and the severity of nonalcoholic fatty liver disease (NAFLD).1 With a well‐characterized and well‐balanced population of biopsy‐proven NAFLD patients, the diversity and composition of gut microbiota were investigated using the MiSeq sequencing platform. Several key functional bacterial phylotypes such as Bacteroides, Prevotella, and Ruminococcus were identified to be associated with the severity of NAFLD. Besides the classical predictors, the present data indicated that the gut microbiota would provide new insights on the diagnosis of NAFLD. For gut microbiomic analysis, both the diversity indices and taxonomic composition were used to define the status of the gut ecosystem. Only alterations of the taxonomic composition, especially those abundant genera, could not determine the status of the gut ecosystem as dysbiosis accurately. Other indices such as α‐diversity, β‐diversity, and Good's coverage would provide more meaningful information for the alterations of the overall structure and composition of gut microbiota. However, the important indices of diversity, such as Shannon and Simpson, seemed to be ignored in the Boursier et al. study as they could stress considerable variation in response to changes in the richness and evenness of the gut microbiota.2 In addition, the Firmicutes/Bacteroidetes ratio was considered to be representative of health status and might be considered an important marker to evaluate eubiosis or dysbiosis of the gut. Without healthy control, the diagnosis of gut dysbiosis might be arbitrary in these patients with NAFLD. For microbiomic biomarker discovery and explanation, the alterations of gut microbiota also could be analyzed by linear discriminant analysis effect size, which would emphasize both statistical significance and biological relevance. Linear discriminant analysis effect size could identify not only the differences of abundant bacteria but also those nonabundant ones. 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. With larger scales of NAFLD patients in different stages, the diagnostic value of these genera with best cutoff levels could be verified. Furthermore, the endotoxin‐induced inflammation was not correlated with those altered genera, which would clarify their relationships in the microbiota‐gut‐liver axis. In conclusion, the study provided new insights; however, the microbiota evaluation and the diagnostic accuracy were still limited. Without a comprehensive understanding of the overall structure and composition of the gut microbiota and the diagnostic value of the key functional bacteria, it was difficult to decipher the real roles of the gut microbiota in the development of NAFLD.