Prathamesh Dongre is a postdoctoral researcher at The Francis Crick Institute. He investigates how high-fat diets alter neuro-immune communication in the gastrointestinal tract to drive inflammation and susceptibility to gut infections. In this Postdoc Portrait interview, he shares what initially drew him to his research.
Uncovering the Intestinal Neural Network
Q | What drew you to the nervous and immune systems?
Since my early scientific training, I have been fascinated by the complex relationship between the nervous and immune systems. Traditionally, the brain was considered an immune-privileged organ with limited capacity to engage in immune responses. However, emerging research has revealed that specialized non-neuronal cells, such as microglia, actively shape immune processes in the brain, and their dysfunction can drive neuroinflammation and neurodegenerative diseases such as Alzheimer’s disease.
During my PhD, I investigated how a mitochondrial protein regulates microglial activation and neuroinflammation during aging and Alzheimer’s disease. This work sparked my broader interest in understanding how cells traditionally viewed as “non-immune” contribute to immune regulation. Driven by this question, my postdoctoral research explores the role of enteric neurons and glia in the gastrointestinal tract, investigating how these specialized neural cells communicate with immune cells to maintain tissue homeostasis and influence inflammatory responses.
Q | What scientific problem are you trying to solve?
Consumption of diets rich in fat is linked to an increased risk of developing intestinal inflammatory disorders. The intestine has a dense intrinsic network of neurons and glia called the enteric nervous system (ENS) that closely interacts with the microbiota and immune system to coordinate gut motility, immune responses and tissue repair. My work aims to understand the effects of different types of dietary fat on the ENS and neuro-immune crosstalk in the intestine that shapes an individual's susceptibility to intestinal disorders and infections. Using mice fed with a high-fat diet, I study how the diet impacts our 'second brain' (the ENS) and influences intestinal motility, gut infections, and neuroimmune interactions.
Decoding Non-Immune Immune Sensing in the Gut
Q | What’s one thing you learned from your research that you didn’t expect?
One of the most surprising things I have learned through my research is that cells traditionally considered “non-immune” can have powerful roles in shaping immune responses. I was particularly fascinated by how these cells sense stress, communicate with immune cells, and influence inflammation. This changed the way I think about biology—not as separate systems working independently, but as a highly connected network where different cell types work together. While working on this research question, I also developed patience, resilience, independence and critical thinking skills, which are essential for almost every part of life. Many unexpected results have provided valuable insights and new directions rather than being setbacks. These lessons have shaped not only how I think about science but also how I approach broad challenges in life with curiosity, persistence, and a willingness to learn from unexpected outcomes.
Q | If your research succeeds, what could it change for science or society?
This work could change how we understand and treat diseases linked to inflammation in the nervous and digestive systems. Our diet is a principal factor that affects our physiology, metabolism and overall health. If we understand how diet affects our nervous system of the gut then contribute to better treatments that are more precise and have fewer side effects, improving quality of life of patients suffering from disorders.
Q | What question are you most excited to answer next?
The question I am most excited to answer next is how exactly do enteric neurons and glial cells in the gut sense dietary and microbial changes and convert those signals into immune responses. I want to understand what molecular pathways allow these non-immune cells to detect changes in the gut environment and then communicate with immune cells to either promote inflammation or maintain balance. This could help explain why certain diets increase susceptibility to inflammatory diseases while others are protective.
Responses have been edited for length and clarity.
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