Gut feelings: What our microbes have to say about healthy aging

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In middle school I was hospitalized for typhoid fever and dengue fever, burning with a 102-104°F fever almost every night with internal bleeding of the stomach. I dropped down to 83 pounds in weight at 5’2 in height at the time, subsisting on a liquid diet because of the sheer amount and strength of antibiotics I had to take during my hospitalization. It was here that I learned for the first time that antibiotics can obliterate the gut microbiome, destroying the balance of beneficial and harmful bacteria in the gut and hence undermining one’s metabolic health and immune defenses.

I distinctly remember, upon arriving back home from the hospital, being gifted Chinese earthworm medicine by a family friend for a speedy recovery, a traditional medicine known to help with inflammation and wound healing. I had forgotten just how much East Asian culture took diet seriously during convalescence. As I tediously, though gratefully, followed the structured diet my mom had for me, I wondered how effective diet can be in building back the body’s immunity. I was told that the purpose of such a diet was to build a healthy gut microbiome first, which would then be naturally followed by restored immunity. This led me to a growing interest in gut microbiome research over the years.

What exactly is the gut microbiome? The gut microbiome is the fascinating community of microbes living in the digestive tract. It is generally agreed to act as a whole organ, functioning in overall host health and metabolism. Not only does it function in digesting key macro nutrients, such as by helping with the digestion of meat by secreting special helpers called enzymes, but it also contributes to the host’s immune system, fighting off infections as needed. However, how exactly the gut microbiome functions to promote host health is not yet well understood. 

We do know, however, that gut microbiome composition and function vary distinctly between healthy and non-healthy individuals, showing distinct abundance of certain bacterial strains in non-healthy individuals when compared to healthy individuals. This suggests that specific gut microbes and their unique properties may be responsible for certain core functions of the gut microbiome in promoting host health. Furthermore, we know that gut microbiome composition changes with age, becoming less diverse over time. This decrease in gut microbial diversity is observed to correlate with a deteriorating function of the gut microbiome as well as with an increased risk of age-associated diseases, such as Alzheimer’s disease and type 2 diabetes. So how and why does the gut microbiome composition of the host change over time? If these correlations between the gut microbiome and healthy aging can be established as causation, how can we target the gut microbiome to improve therapies for age-associated diseases?

A tiny transparent worm helps study the aging process

In this context, I am planning to explore these questions using an animal model called Caenorhabditis elegans. Among many of its strengths, the C. elegans model has a short lifespan of 2-3 weeks, a transparent body, and a resource of 12 strains representative of its native gut microbiome that can be efficiently maintained in laboratory settings. Additionally, this worm is bacterivorous, allowing for precise control of its diet and thus of its gut microbial content. All of these factors combined make this worm a suitable model to study and observe the dynamic host-microbial interactions of its gut microbiome.

I am starting out by narrowing down the number of bacterial strains to be studied, by measuring the effect of each strain on host longevity, mobility and feeding behavior, as well as immune response. I plan to explore each relevant strain’s bacterial metabolite production, which are the chemicals they produce to communicate with the host, as well as how their gene activity changes when they colonize the C. elegans gut. Laying down this groundwork will help us understand which bacterial strains extend worm lifespan and by which molecular mechanisms they do so.

Eventually, understanding the bacterial strains’ properties, their interactions with the host, and the different host responses to different bacterial strains, will help us understand gut microbiome dynamics. This could potentially become the key to understanding the aging process, providing efficient targets in the gut microbiome for improved host health, improved stress resistance, and thus improved prognosis in age-associated diseases.