In brief

A*STAR National Science Scholar Phyllis Phuah shares her motivations for delving into obesity research, with a focus on host-diet-microbiome interactions.

© A*STAR Research

Making metabolic sense of microbes

10 Nov 2023

A*STAR scholar Phyllis Phuah aims to develop better treatments for metabolic diseases by understanding how gut microbes help (or hinder) the connections between our body and brain.

To achieve peak performance, athletes follow strict diet plans mapped out by nutrition specialists. Bodybuilders alternate between scheduled ‘cuts’ and ‘bulks’ to attain the perfect physique. Frail patients in healthcare facilities are advised on planned meals and supplements to meet their nutritional needs.

For the rest of us, the question “what to eat, and when?” is often answered with what our body tells us. We feel that ‘talk’ as physical signals: lethargy, hunger pangs, a dry (or watering) mouth.

Behind those signals, however, are complex interactions between networks of cells, nerves and organs throughout our body. They monitor our internal environment and prompt our brain about our needs—more salt or sugar?—to keep it in a state of chemical and physical balance, or homeostasis.

What we eat adds another layer of complexity to those interactions. For example, the communities of bacteria that reside in our gut—our microbiome—produce their own metabolites, which can upset the healthy balance our body tries to maintain. Certain foods can promote or hinder the development of different bacterial species, altering the microbiome in ways that have knock-on effects on our bodies, for better or worse.

At A*STAR’s Institute of Molecular and Cell Biology (IMCB), Phyllis Phuah works alongside others in the Brain-Body Initiative (BBI) to learn more of how the interactions between the body, diet and microbiome impact human health. Understanding these links could help us develop better treatments for metabolic diseases like type 2 diabetes (T2D) and obesity.

In this interview with A*STAR Research, the National Science Scholar shares how her love for biology and fitness led to her interest in obesity research, and her advice for researchers aspiring to study neurometabolism.

Q: What sparked your interest in neurometabolism research?

During my undergraduate studies at Imperial College London, one of most interesting lectures I attended was on anti-obesity drugs. This was when I first learnt that some of the most promising drug therapies in the obesity field involved manipulating the normal gut hormone system to induce satiety and reduce appetite.

I was deeply intrigued and wanted to better understand the science underpinning anti-obesity drugs. Furthermore, as a fitness enthusiast, I enjoy reading about exercise physiology, different diets like intermittent fasting, keto and ‘performance-enhancing’ nutrition. Studying obesity felt like a natural fit. Furthermore, with the rising numbers of individuals living with metabolic diseases globally, I thought that contributing to obesity research would be deeply meaningful and impactful.

I reached out to the lecturer, Kevin Murphy, and the rest is history. I undertook a PhD degree under his supervision, which was where I started my research in neuroendocrinology.

Q: Tell us about your journey as a young researcher.

I had always enjoyed biology lessons in school because I love learning about how the human body works. Applying for the National Science Scholarship felt like an obvious choice; it provided me with the opportunity to pursue a world-class education for both my undergraduate and PhD studies.

During this time, I grew both as a scientific thinker and as a person. I learnt so much about good science from the many brilliant scientists within my department and built professional networks at international conferences.

For my PhD degree, I studied indole (a gut microbial metabolite) and its effects on hormone secretion and glucose control. I also developed a keen appreciation for the gut-brain axis. I found it fascinating how the gut, which senses nutrients consumed during a meal, communicates with the brain to regulate body functions like energy homeostasis. Some questions I’ve always wondered about started to make sense—how do we know when to stop eating? Why do we feel ‘hangry’ when we haven’t eaten?

I was intrigued to further pursue this area of research. I was quite fortunate that there was a cluster of neurometabolism labs at IMCB, and the BBI research programme was just starting up in A*STAR towards the end of my PhD studies. It all aligned perfectly with my research interests and created an exciting space for me to contribute to after I returned to Singapore.

Q: Can you tell us about your current work at A*STAR?

As a postdoctoral research fellow in Sarah Luo’s lab, I’ve been part of the collaborative BBI to better understand host-diet-microbiome interactions—which has been very exciting!

Using data obtained from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study, we’ve identified some microbe species that appear to correlate with signatures of metabolic health or disease. We are now validating these targets using a range of in vivo models and are hoping to identify specific microbes that can modulate human metabolic health. One method could be through prebiotic supplementation.

Another project I’ve been working on looks at teasing out liver-brain neural circuits. We’re interested in identifying novel brain regions that are connected to the liver and understanding how these regions may regulate liver function in both health and disease.

Q: Why are metabolic brain-body circuits worth knowing better?

I strongly believe that a better understanding of normal human physiology—such as the neural circuits governing feeding and energy expenditure—provides important insights into disease states, like obesity, that can help us identify novel therapeutic targets.

Such research has never been more relevant given the global epidemic of obesity and T2D. One example that comes to mind is the new weight loss drug, tirzapetide, which was developed based on our understanding of how gut hormones normally work in the body to induce satiety and enhance insulin secretion.

In recent years, there have been many exciting new advances in neurobiology that have really shaped our understanding of how our body senses and integrates internal signals to regulate homeostasis. We also now know that in obesity, many of these neural circuits implicated in feeding and reward are dysregulated.

I believe that we’re only at the tip of the iceberg of unravelling the complexities of brain-body circuits. We’re only beginning to appreciate the role of inter-organ neural circuits in metabolic regulation. I think it is exciting that many research groups have started moving beyond the gut. They’re looking at other densely innervated peripheral metabolic organs—like the liver, pancreas and fat—and how they communicate with the brain or with each other to influence organ function.

Q: What do you hope to achieve as a young researcher?

I hope that my contributions to the research field of neurometabolism will translate into real-world impact. Ultimately, I hope that my work will help to improve human health by identifying novel interventions for the prevention or treatment of chronic metabolic conditions, which will help people enjoy a better quality of life as they live longer.

I also hope that improving the visibility of young female scientists and participating in scientific outreach activities will inspire future generations, especially women, to pursue STEM as a career whether in research or beyond.

Q: What advice would you offer young STEM talent?

A career in research is a marathon and not a sprint. The most important thing is to never give up. As scientists, we are constantly exposed to failure, and so we must remember not to take it personally and to keep trying again, no matter how daunting it may seem.

Also, treat every day like a school day. The research landscape in Singapore, and science itself, is ever changing. It is so important to keep relevant by staying open to new ideas and learning constantly.

Lastly, don’t be afraid to advocate for yourself by seeking out good mentors who can guide and support you along the way.

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This article was made for A*STAR Research by Wildtype Media Group