Whether reaching for more food or deciding between two choices on a test, trusting one’s gut is often a good idea. More than just a catchy expression, it turns out that listening to signals from the gut—consciously, or otherwise—can influence neural circuitry and behavioural decisions.
This unique relationship between the digestive and nervous systems, alongside the complex mechanisms that govern how they interact, is the focal point of emerging research led by Hwei Ee Tan, a Junior Investigator at A*STAR’s Institute of Molecular and Cell Biology (IMCB).
A sensory neuroscientist by training, Tan expanded his repertoire to investigating the microorganisms that live along the digestive tract and help break down food—the gut microbiome. He believes that there is more to this tiny world than just facilitating nutrition.
Through the wiring that links the gut to the nervous system, the gut microbiome may be important for modifying many neural functions such as behaviour, mood and cognitive abilities. By investigating the connection between diet, gut and brain, Tan and his colleagues are on a mission to uncover how intestinal microflora can influence our health.
Q: What sparked your interest in the gut microbiome?
It started when I lost 15 kg in just a few months, much to my amazement. I had been following a ketogenic diet which involved limiting my daily carbohydrate sugar intake to less than 20 g—for reference, a plain bagel has 50 g of carbohydrates. This dramatic weight loss also coincided with a uniquely stressful period during my PhD training at Columbia University and my new fitness regime, among other lifestyle changes, so I could not conclude how much my diet alone contributed to my weight loss.
However, in the process of limiting my carbohydrate sugar intake, I read up about a type of non-digestible carbohydrate called dietary fibre and its impact on the microbiome, and came across academic papers that described how germ-free animals are resistant to diet-induced obesity. Astonishingly, transferring the bacteria from obese individuals into germ-free mice was sufficient to induce aspects of obesity in the recipient mice, suggesting that the microbiome causally contributes to health and disease.
Fascinated by this, I wrote to professors in our microbiology department and sat in on their microbiome courses. From there, I was introduced to seminal works by various groups around the world in the emerging field of microbiome science.
Q: Tell us about your research journey to date.
My research journey started in molecular and developmental biology. As an undergraduate intern at the University of California, Berkeley, I studied the biological development of structural colouration in the wing scales of butterflies and moths. From iridescent blues to vibrant purples, some wing colours come from nanostructures that bend light.
In the following year, I studied the other side of this phenomenon: how do we see light and its component colours? Through an exchange programme at Osaka University, my research focused on rhodopsin, the molecule that converts light into biochemical signals in our cells.
However, sensing is not the same as perceiving, which happens higher up in the brain. As such, in graduate school I decided to study how sensory stimuli are perceived in our brains. At Columbia University, we studied the perception of taste. To mice and humans, sweet compounds are universally attractive and bitter compounds are innately aversive. We dissected how taste stimuli activate consistent brain circuits that lead to these reactions. Serendipitously, we found taste is dispensable for sugar preference, and subsequently uncovered novel gut-to-brain circuits that mediate sugar and fat preferences.
Upon returning to Singapore, I joined IMCB to conduct independent, postdoctoral research on the microbiome and gut-brain axis. I also secured additional research support from the Young Individual Research Grant by the National Medical Research Council; and the LKCMedicine-Imperial College London postdoctoral fellowship under Nanyang Technological University, Singapore.
Q: Can you tell us more about your ongoing research?
Phrases such as ‘gut feelings’ and ‘butterflies in my stomach’ suggest that elements in our gut shape our emotions and behaviours. In fact, the gut microbiome is associated with many aspects of health and behaviour—from metabolic health and eating disorders to cognition and depression.
This realisation aligns with the research I have been working on. Over the past years, my colleagues and I have discovered how nutrients in our food activate a neural circuit from the intestines to the brain. I wondered whether this circuit, commonly referred to as the gut-brain axis, could also explain how diet and microbiome interactions influence our health and behaviours. More recently, our research has demonstrated exciting evidence that substrates in our gut engage specific neural circuits in the brain to influence internal states and behaviours.
Q: How do you see your research evolving in the next few years?
The Human Genome Project has already dramatically transformed society, health and medicine. Now, another genomic revolution marked by the Human Microbiome Project is catalysing rapid advances in our understanding of the microbiome. Collectively, the bacteria living in our body encode over 46 million genes, whereas the human genome encodes less than a thousandth of that. Its sheer diversity and size make studying the microbiome far more challenging, but also represent the immense potential of such research endeavours.
Elucidating the biological mechanisms of the gut-brain axis, especially including the contribution of the complex gut microbiome, will require continued investment in basic research and will rely on multidisciplinary, collaborative teams. By working together with the various neuroscience and microbiome research groups in Singapore, as well as international collaborators, I hope our research can unveil important insights on the microbiome-gut-brain axis in the years to come.
Q: What advice can you share with students hoping to pursue a career in research?
I consider a career in research more of a lifestyle choice than a job. I find joy in testing ideas, troubleshooting problems and making discoveries, so a research career is an excellent fit for me.
The research process involves a lot of trial-and-error and navigating obstacles that come our way, so resilience and problem-solving skills are important. We are also more likely to stay motivated and driven if we find the science that captivates and excites us. To find their passion, I encourage students to experience a variety of research areas by taking advantage of the wealth of science opportunities in Singapore and abroad.
