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Doctoral defence of Ambrin Farizah Babu, MSc, 27 Oct 2023: Unlocking metabolic insights of lifestyle interventions and microbiome therapeutics for NAFLD

The doctoral dissertation in the field of Nutrition will be examined at the Faculty of Health Sciences at Kuopio campus. The public examination will be streamed online.

What is the topic of your doctoral research? Why is it important to study the topic?

My doctoral research focusses on metabolomics, the analysis of small molecules, known as metabolites, within biological systems. This research field holds immense importance in health sciences as it unravels metabolic processes, sheds light on disease mechanisms, potentially identifies diagnostic biomarkers, and assesses the effectiveness of disease treatments.

Specifically, my research showcases the application of metabolomics in the research on non-alcoholic fatty liver disease (NAFLD), the most common cause of chronic liver diseases worldwide. The study also reveals the metabolic alterations and responses to various NAFLD treatments, including lifestyle changes and novel microbiome-based therapeutics. By advancing our knowledge in this area, we aim to address the challenges posed by NAFLD and enhance the quality of life for those affected by this condition.

What are the key findings or observations of your doctoral research?

In this study, I have investigated the applicability of metabolomics in NAFLD research due to the increasing prevalence, limited knowledge of the disease biomarkers and pathogenesis, and the lack of approved pharmacological therapies for NAFLD. Through metabolomic analysis, we identified significant changes in metabolites, including amino acids, lipids, and compounds originating from the gut microbiota, that played pivotal roles in the observed health benefits resulting from exercise, diet, and microbiome therapeutic interventions.

A primary outcome of this research was gaining a clearer understanding of the effectiveness of lifestyle modifications and novel microbiome-based therapeutics in mitigating NAFLD. These interventions showed promise in addressing the disease, offering hope to patients seeking non-pharmacological approaches for NAFLD management. Importantly, we discovered that the positive effects of these interventions extended beyond the liver. Our findings unveiled a systemic impact, involving intricate interactions among the gut microbiota, circulatory system, excretory processes, and tissue metabolism. This comprehensive understanding is crucial for devising holistic treatment strategies for NAFLD.

How can the results of your doctoral research be utilised in practice?

The results of my doctoral research validate the utility and reliability of LC-MS-based metabolomics in NAFLD research. This validation is crucial for establishing a robust foundation for future investigations, clinical trials, and experimental studies aimed at advancing our understanding of NAFLD and its potential treatments. The metabolomics approach employed in this thesis is a useful tool for unravelling crucial metabolic alterations and the associated pathways involved in NAFLD pathogenesis. This methodology can be readily adopted by researchers and clinicians to gain deeper insights into the metabolic aspects of NAFLD and evaluate treatment strategies for the disease.

The semi-targeted LC-MS approach presented in Study I offers a practical and efficient means to screen for NAFLD-related metabolites (sterols, bile acids, and acylcarnitines), which can prove invaluable in routine scientific research. Researchers can leverage this methodology to identify and quantify relevant metabolites, thereby streamlining the research process.

The identification of metabolic alterations in humans following exercise (Study II) enhanced our comprehension of the underlying mechanisms of how exercise benefits NAFLD subjects. This insight could lead to the development of exercise-based interventions or pharmacological agents tailored to alleviate NAFLD.

The combination of engineered E.coli Nissle 1917 expressing aldafermin with dietary changes, as explored in Study III, may pave the way for the development of novel therapeutic interventions for NAFLD, offering new avenues for research and drug development.

What are the key research methods and materials used in your doctoral research?

In my doctoral research, I employed a semi-targeted LC-MS based metabolomics approach to simultaneously detect the occurrence and distributions of NAFLD-related biomarkers in biological samples. Thereafter, nontargeted metabolic profiling, a comprehensive approach that enables a holistic examination of metabolites with diverse chemical properties, was utilized to decipher the effects of exercise in humans and a combined dietary and microbiome therapeutic intervention in mice. To ensure the robustness and applicability of my findings, I analyzed a wide variety of biological samples, encompassing humans, mice, and pigs. This enhanced the relevance and translatability of my research. Moreover, I investigated the effects of the interventions in multiple sample matrices including liver, plasma, adipose tissue, luminal contents, gut tissues, and bile to gain a comprehensive understanding of the metabolic alterations.

The doctoral dissertation of Ambrin Farizah Babu, MSc, entitled A metabolomics approach to delineate the effects of lifestyle intervention and microbiome therapeutics in non-alcoholic fatty liver disease will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Senior Lecturer Cristina Legido-Quigley of King’s College London, and the Custos will be Professor, Research Director Kati Hanhineva of the University of Turku and the University of Eastern Finland.

Doctoral defence

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Dissertation

For further information, please contact:

Ambrin Farizah Babu, MSc, ambrin.babu(a)uef.fi, +358452030433, https://uefconnect.uef.fi/en/person/ambrin-farizah.babu/