Branched-chain amino acids linked to gut microbiome and insulin resistance

Duration: 6 months (Dec 2016-May 2017)
Project type: Voluntary Master’s research project
Supervisors: Dr. Jingyuan Fu and Prof. Sasha Zhernakova

Hi! I am Marwah Doestzada, I’m a medical student now in my last year. In December 2016, I started a Master’s research project with Jingyuan Fu and Sasha Zhernakova in the Microbiome group at the Department of Genetics.

Before this I had performed two research projects at the Department of Neuroscience: one in which I focused on changes in the central nervous system leading to fatigue and also learned most of my statistical skills (this led to becoming a co-author on a paper in J Appl Physiology *), while the other project for my Master’s research period was working on the expression and successful isolation of the human potassium channel Kv4.3, to start understanding why mutations in this channel can cause both neurodegeneration and cardiac arrhythmias. I had a great time and gained a lot of scientific skills and experience, and by doing two completely different projects I also got a clear idea of what I wanted to do for my voluntary research project: understand disease mechanisms and use the knowledge to prevent diseases, and systems biology is one of the best tools for this!

Therefore, I approached Dr. Jingyuan Fu and chose to work on the gut microbiome. I had a good time but it was also lots of hard work, but luckily the supervision was great and everyone is approachable and stimulates you to do more with your project. My research aimed to understand why essential amino acids are increased in people with insulin resistance (which is dysregulated in people with diabetes) and how much the microbiome influences this. I found that several microbial pathways contribute to blood levels of these amino acids and through this route they also contribute to insulin resistance. Furthermore, I showed that the gut microbiome mainly affects insulin resistance via its role on the essential amino acid isoleucine (manuscript submitted to eLife).

The internship worked out quite well and I was awarded an MD/PhD position to continue with research on the gut microbiome and metabolic disease, focusing specifically on non-alcoholic fatty liver disease (NAFLD). NALFD is present in 20-30% of the global population and is now the most common cause of chronic liver disease worldwide. It is not clear how NAFLD progresses from a simple form with no symptoms, to severe end-stage liver trauma that cannot be treated. During my PhD work I will focus on identifying the microbial components contributing to this progression, starting from insulin resistance and moving on to the severity of the disease by looking at steatosis, inflammation and changes in the function of the liver. My aim for my MD/PhD is to understand the mechanisms and highlight the potential of using gut microbiota as biomarkers for the progression and treatment of NAFLD.

* Prak RF, Doestzada M, Thomas CK, Tepper M, Zijdewind I. Reduced voluntary drive during sustained but not during brief maximal voluntary contractions in the first dorsal interosseous weakened by spinal cord injury. J Appl Physiol. 2015;119(11):1320–9.