Using metabolomics to develop precision medicine strategies to treat nonalcoholic steatohepatitis

ABSTRACT

Introduction: Nonalcoholic fatty liver disease (NAFLD) is a health problem of global concern. Nonalcoholic steatohepatitis (NASH), the advanced form of NAFLD, is considered a complex disease and despite the efforts of the medical and researcher community, the current knowledge about it is still limited. As occurs in other medical disciplines, NASH research can benefit from precision medicine approaches. Because the metabolome is highly sensitive to genetic and environmental changes, metabolomics is presently being considered a powerful tool for precision medicine.

Areas covered: This review focusses on metabolomics applications in the field of NAFLD/NASH research. We overview metabolomics studies used for a better understanding of factors that act as modifiers of NAFLD susceptibility and progression, such as lifestyle and genetic factors, dysbiosis, and concomitant diseases. We also review applications in the search of noninvasive biomarkers for diagnosis, intervention response, patient stratification and monitoring.

Expert opinion: Metabolomics, and especially its branch lipidomics, are ideally placed to study diseases related to deranged lipid metabolism. The search of noninvasive panels able to diagnose NASH and stage fibrosis has become the main application of metabolomics in the NASH/NAFLD field. However, the prediction of patient’s response to treatments is one of the most promising strategies.

KEYWORDS:

• Metabolomic phenotyping
• noninvasive diagnostic biomarkers
• drug development
• response to therapy
• genetically influenced metabotypes
• microbiome

Article Highlights

• The natural history of NAFLD and NASH can be influenced by dietary, lifestyle and genetic factors, an imbalance in gut microbiota, and the presence of concomitant diseases.

• Lipidomics is ideally placed to study diseases related to deranged lipid metabolism.

• Genome-scale metabolic modeling approaches are valuable for the understanding of the genotype-phenotype relationship.

• Pharmacometabolomics is one of the most promising strategies in precision medicine and can help to predict patient’s response to treatments. The development of models where the drug and the companion diagnostic are developed in parallel could be more effective than the ‘one-fil-all’ approach.

• The selection of a target patient population provides the opportunity to increase drug efficacy. Clinical trials should be designed considering the patient heterogeneity, stratifying the NASH patients and determining the drug effectiveness based on this stratification.

• Noninvasive biomarkers for the identification of patients at risk of the disease are also useful for facilitating patient screening for inclusion in clinical trials.

• Understanding how broadly host-microbiome associations are maintained across populations may reveal individualized host-microbiome phenotypes.

Declaration of interest

Dr. Iruarrizaga-Lejarreta, Dr. Arretxe and Dr. Alonso are employees of OWL Metabolomics. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.