Evolving microbes to promote host longevity
Work done in the lab of Dr. Scott F. Leiser at University of Michigan
Dr. Ajay Bhat is a Postdoctoral Fellow at the University of Michigan’s Department of Molecular and Integrative Physiology in the USA. Born in Kashmir, the northern part of India, his family was forced to migrate to Jammu when he was four years old due to insurgency and targeted violence, where he was raised in a refugee camp. Despite these challenging circumstances, his parents supported his education, giving him the opportunity to pursue academic success. Dr. Bhat earned his Master’s degree from Jiwaji University in Gwalior and his Ph.D. from the Institute of Genomics and Integrative Biology in Delhi. His Ph.D. thesis discovered the mechanism of cysteine-induced growth defects in yeast and identified the genetic pathways necessary for survival during high cysteine levels. He then moved to the University of Michigan, USA, for his postdoctoral studies, focusing on understanding the role of metabolism in regulating aging. Recognizing that aging is the biggest risk factor for many metabolic and neurological diseases, Dr. Bhat aims to understand the biology of aging, with a specific interest in nutrition, stress response, and metabolism. Currently, Dr. Bhat is interested in understanding how stress response pathways in microbes can regulate stress signaling, metabolism, and aging in host organisms.
Author Interview
How would you explain your research outcomes to the non-scientific community?
We often encounter emotional stress stemming from our work or personal environment. When faced with these stresses, we each have our ways of coping, such as exercising, going for a walk, listening to music, or seeking support from loved ones. Similarly, our bodies frequently encounter various stressors such as changes in temperature, exposure to toxic chemicals from our environment or our own metabolism, and significant changes in our dietary conditions. To survive and cope with stress, our cells in the body activate certain signaling pathways in response to these stressors, a process known as the stress response. However, as we age, our ability to handle stress declines, which is associated with age-related disorders. Additionally, our bodies also host a vast population of microorganisms, collectively known as the microbiome. In their shared environment, these microbes experience the same stressors and activate their own survival pathways. Because they have short generation time and reproduce quickly, they can adapt and evolve much faster than we can. In this study, we evolved bacteria to resist paraquat, a chemical that causes oxidative stress, which is a type of stress that accumulates with age. We used a roundworm called Caenorhabditis elegans, which in its natural environment lives in soil and decaying fruit/plant material, as a host to study the effects of these evolved bacteria. In the laboratory, we found that when these worms were fed the evolved bacterial strains, they could handle stress better and lived longer. We discovered that evolution targeted the iron metabolism in the bacteria, leading to higher levels of iron. These high levels of iron helped the worms eating these bacteria to live longer and tolerate stress better.
“Our study suggests that targeting microbial evolution could pave the way for developing personalized probiotics to combat age-related diseases”
How do these findings contribute to your research area?
Aging is associated with decreased stress response and alterations in microbiome diversity. Microbes live in close association with their host; however, how microbial stress signals impact stress signaling and lifespan in hosts has remained unclear. Our research shows that stress-induced adaptive evolution can modify microbial metabolism, thereby improving stress tolerance and lifespan in hosts. We discovered that iron from these evolved microbes activates the innate immune response pathway in worms, contributing to their increased longevity. If these findings prove applicable in mammalian systems with complex microbiomes, our study suggests that targeting microbial evolution could pave the way for developing personalized probiotics to combat age-related diseases.
What was the exciting moment during your research?
The most exciting moment during our research was when we observed that the evolved microbial strains not only enhanced stress tolerance in the worms but also significantly extended their lifespan. This discovery ignited our determination to delve deeper into the project, driving us to unravel the intricate mechanisms behind these beneficial effects.
What do you hope to do next?
There are several aspects of this research we are eager to explore further. Firstly, we aim to determine if the interaction we discovered is specific to oxidative stress. Currently, we are repeating these experiments using heat, osmotic, and nutritional stress to investigate broader applicability. Secondly, we are investigating whether this interaction holds true within complex microbiomes and in mammalian systems. This exploration will help us understand the broader implications and potential applications of our findings across different biological contexts.
Where do you seek scientific inspiration from?
I find scientific inspiration through reading literature and engaging in scientific discussion with my colleagues and mentors.
How do you intend to help Indian science improve?
My goal to enhance Indian science involves training the next generation of scientists. This includes raising awareness among them early in their careers and showcasing the excitement of scientific discovery. Even though I am in the USA, I plan to achieve this by collaborating with institutes in India and participating in workshops and conferences. In future, if given the opportunity, I would also like to visit schools in India to engage with students and inspire their interest in science.
Reference: Bhat. A* & Cox. RL* et al, A diet of oxidative stress–adapted bacteria improves stress resistance and lifespan in C. elegans via p38-MAPK.Sci. Adv.10, eadk8823(2024).DOI:10.1126/sciadv.adk8823. * Equal Contribution
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