Dynamic shifts in the bacterial composition of the human gut microbiome have been found to carry profound implications in advanced disease progression of several types of carcinomas, including those linked to nonalcoholic fatty liver diseases (NAFLD)1. Additionally, the presence of progressed liver fibrosis has proved to be a key predictor of long-term liver-related complications in patients diagnosed with NAFLD2. Studies show that increased bacterial overgrowth favors extreme inflammatory responses in patients with advanced NAFLD progression-related liver fibrosis3. Non-invasive diagnoses of advanced fibrosis also poses a significant clinical roadblock.

A Fecal Microbiome-Derived Detection Method

Researchers at University of California, San Diego carried out a prospective study to assess the role of gut microbiome-based metabolic signatures in the detection of advanced fibrosis in NAFLD. The researchers identified significant differences in taxonomic compositions of gut microbiomes of NAFLD patients . They identified 37 bacterial species that were used as features to construct a Random Forest classifier model and could distinguish between mild/moderate and advanced fibrosis patients with a significant diagnostic accuracy of area under the curve (AUC) 0.936.

Microbiota as Biomarkers for NAFLD

Whole genome shotgun sequencing was used to determine the gut microbiome compositions of fecal matter derived from NAFLD patients. Gut microbiota present in both mild/moderate and advanced staged fibrosis patients consisted of Firmicutes and Bacteroidetes followed by Proteobacteria and Actinobacteria
in much lower abundances. It was noted that the population of Firmicutes decreased while that of Proteobacteria increased significantly in patients in the advanced stages of fibrosis. Additionally, B. vulagtus and E. rectale were observed to be the most abundant species present in such patients.

Innovative Characterization of NAFLD

The authors carried out a detailed phenotypic assessment of biopsy proven NAFLD that integrated stool metagenomic profiling with serum metabolomics of the patient’s samples. The diagnostic accuracy of biome derived biomarkers was further confirmed by performing MR imaging of the well-characterized cohorts.

The results reflected that in patients with advanced stages of NAFLD linked fibrosis, the trend in microbiota shifted towards an abundance of gram-negative bacteria. The study did not rule out the possibility of the list of 37 bacterial species described to be ultimate and exhaustive, it suggests that there could be additional microbial species that could function as biomarkers for advanced fibrosis.

Exploring Metabolic Pathways for Developing Advanced Diagnostic Tools

Metagenomics signatures are set to used extensively as diagnostic tools for a multitude of diseases in the future and studies such as these provide a non-invasive alternative for quick detection and prediction of fatal diseases4. Further investigations into replacement of gut microbiota in liver disease patients through techniques like fecal transplantation and probiotics open up new avenues for research and therapy development.

Link to the original publication: Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease

References:

1. Adams, L.A., Lymp, J.F., St Sauver, J., Sanderson, S.O., Lindor, K.D., Feldstein, A., and Angulo, P. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 129, 113–121 (2005).

2. Dulai, P.S., Singh, S., Patel, J., Soni, M., Prokop, L.J., Younossi, Z., Sebastiani, G., Ekstedt, M., Hagstrom, H., Nasr, P., et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis. Hepatology. Published Online (2017).

3. Turnbaugh, P., Hamady, M., Yatsunenko, T. et al. A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2009).

4. Lining Guo, Michael V. Milburn, John A. Ryals, Shaun C. Lonergan, Matthew W. Mitchell, Jacob E. Wulff, Danny C. Alexander, Anne M. Evans, Brandi Bridgewater, Luke Miller, Manuel L. Gonzalez-Garay, C. Thomas Caskey. Proceedings of the National Academy of Sciences Sep, 112 (35) E4901-E4910 (2015).