The doctoral dissertation in the field of Biomedical Physiology 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 focuses on host-microbiota interactions in metabolic dysfunction-associated steatotic liver disease (MASLD) and investigates advanced microbiome therapeutics as innovative microbial-hormonal interventions for early-stage MASLD.
MASLD affects about 30% of adults globally and can progress to severe liver conditions such as cirrhosis and liver cancer. Current treatments rely mainly on lifestyle changes, which are often difficult to maintain and not always effective.
A major challenge for studying MASLD and developing effective treatment is that it is a complex, multifactorial condition involving disruptions in lipid metabolism, hormonal signaling, and gut-liver axis physiology, all influenced by genetic, dietary, and microbial factors. Studying these interconnected mechanisms is essential for understanding disease progression and for developing multi-targeted strategies that can overcome the limitations of current therapies and reduce the global health burden.
What are the key findings or observations of your doctoral research?
In my doctoral research, we demonstrated that gut microbiota and the metabolites in the gut are strongly linked with the expression of MASLD-related liver genes, emphasising the significance of the gut-liver axis during MASLD progression. Specific alterations related to gut dysbiosis, hormonal imbalance, and metabolic disruptions, which contributed to MASLD development, were identified.
We also investigated the use of advanced microbiome therapeutics (AMTs) based on engineered E. coli Nissle 1917 strains producing therapeutic hormones IGF1 or aldafermin (a non-tumorigenic FGF19 analogue) for treating early-stage MASLD in a mouse model. These treatments, combined with dietary changes, effectively alleviated MASLD symptoms, including reduced liver fat, lowered cholesterol levels, promoted weight loss, improved gut microbial diversity, and increased beneficial metabolites.
How can the results of your doctoral research be utilised in practice?
Our findings open the door for microbiome-based precision therapies for MASLD and complex metabolic disorders. Engineered probiotics could provide a non-invasive, oral alternative to injectable hormone therapies, improving patient compliance. These therapies could complement lifestyle interventions, making treatment more effective and personalised.
Although we demonstrated promising effectiveness in a preclinical model, further steps are needed before clinical application, including safety evaluations, long-term stability studies, and regulatory approvals. Nevertheless, our research provides a strong foundation for developing innovative, microbiome-based strategies that could tackle the current limitations of MASLD treatment.
What are the key research methods and materials used in your doctoral research?
We used a C57BL/6J male mouse model fed an American Lifestyle-Induced Obesity Syndrome (ALIOS) diet to mimic and track early-stage MASLD development. To evaluate novel treatments, we tested engineered E. coli Nissle 1917 strains expressing IGF1 or aldafermin, delivered orally in gelatine cubes, alongside dietary changes in mice with established early-stage MASLD. Various analytical approaches, including blood biochemistry, liver histology, magnetic resonance imaging, 16S and ITS rRNA sequencing, non-targeted metabolomics, and hepatic gene expression analysis, were applied to investigate host-microbiota interactions within the gut-liver axis and the therapeutic effects of these treatments.
The doctoral dissertation of Johnson Lok, MSc, entitled Host-microbiota interactions in MASLD: from disease progression to microbiome-based therapeutics − Gut-liver axis and engineered microbiome-based hormonal therapeutics in a male C57BL/6J mouse model of diet-induced MASLD will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Professor Alice H. Lichtenstein of Tufts University, and the Custos will be Professor Hani El-Nezami of the University of Eastern Finland. The public examination will be held in English.
Doctoral dissertation
For further information, please contact:
Johnson Lok, MSc, [email protected], +358415697048, https://uefconnect.uef.fi/johnson.lok/
