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The Invisible in Us

Joined by three knowledgeable microbiome researchers, Dr. Jonathan B. Clayton, Dr. Shivdeep Hayer, and Mackenzie Conrin, M.S, I learn more about the microscopic complexities within us. Exploring a path based upon minute observation may be tough, but the Clayton Lab, located at the University of Nebraska, proves that with passion and great effort comes appreciable outcomes.

 

The microbiome encompasses the entirety of our microorganismal community. Whether it be within our bodies, in our soil, or in our plants, this ecosystem plays a keystone role in our everyday lives and health.


But why? Why are microbes so important to understand?


"The sum of the parts is greater than the whole," explains Conrin.

While our microbiome itself functions as one entity, it incorporates the billions of microorganisms that each have their own functions in sustaining a larger purpose for our bodies. Dr. Clayton further elaborates that microbes can perform necessary tasks that hosts themselves cannot. A strong example of this is the catabolic process of digesting cellulose that many organisms cannot carry out on their own.


This interwoven dependence on microbes allows us and other species to derive energy from a broader spectrum of food that may not be consumable otherwise.


Another noteworthy, microbial impact concerns our immune system and psychological wellbeing. As Clayton and his team further explore the microbial world, they aim to discover the impact of our exposure to microbes at birth. Based on the microbes we experience from infancy, we develop certain immunological abilities that impact our health. The microbiota-gut-brain axis is one demonstration of how our microbes can intertwine with our mental health and diseases.

Now that the importance of the microbiome is brought to light, how do we go about actually exploring it?


Well, when investigating the microbiome, the range of potential models is numerous.


Trying to maximize the outcome of a study is nothing new for the University of Nebraska’s talented team, but in regards to understanding our own microbiomes, how can research be conducted effectively? There are a plethora of ethical and legal restrictions on studying humans, so the real question is how can researchers narrow down their focus to species that are more easily observable?


Enter the nonhuman primates.


With a highly similar genome to ours, nonhuman primates make for model species that have comparable microbial conditions to humans. Such a correlation allows labs, such as Clayton's, to thoroughly investigate our intricate microbial network. This is a reason, among many others, that Dr. Clayton, along with his colleagues, founded the Primate Microbiome Project.


The microbiome is particularly complex since it is individual-specific. To add to the complexity, it is site-specific, which means that each microbiome within a particular area of one's body or environment is unique due to the conditions it's exposed to.


Resultantly, complex subjects require complex procedures in order to be studied.


Observation and analysis are far from a walk in the park. Fecal samples are great, noninvasive ways to observe the gut microbes of an individual; however, Dr. Hayer notes the flaws with using this evidence for different contexts. A single fecal sample can only represent a microbiome at the point in time it was produced, which is not ideal since the microbiome is always changing. This means that multiple fecal samples over time should be collected to best understand the complete microbiome of a subject and get the best picture of how that subject's body is adjusting throughout time. Once samples are collected, they are stored in ethanol and frozen to halt the growth and transformation of the microbes.


Following collection, samples are used to extract microbial DNA, which is used to generate next-generation sequencing data. This data is subjected to complex data analysis pipelines in order to paint a picture of the microbes present and break down the meaning of the microbial signatures present in the samples. A couple of examples that microbial researchers may look for is dysbiosis, which refers to an imbalance in microbial populations.


When performing their research, Clayton, Hayer, and Conrin utilize a nonhuman primate model, the common marmoset (Callithrix jacchus). This is due to the closely related behaviors to humans that this species exhibits, such as group living and separation anxiety.


When conducting the experiments, manipulations are performed and their resulting effects on the marmoset microbiome are recorded and analyzed. If there is a significant decrease or increase in the population of one particular microbe, then that microbe is of utmost interest due to its potential effects on the host. The microbiota-gut-brain axis is a current research area of interest for the Clayton Lab. In addition to looking at their microbiomes, marmosets are observed for potential changes in behavior, such as rates of interaction between mates.


With all of the conclusions and processes developed so far, it is important to note that the in-depth study of host-associated microbiomes is still just beginning. The road to understanding the mechanisms behind microbes is incredibly diverse and complicated and remains unclear in many aspects. That’s not to say that there haven’t been significant breakthroughs, however. New discoveries are being made that reveal more about our microbiomes with every passing year.


At one point in time, the significance of gut bacterial communities was overlooked.


Now, they are seen as powerhouses that can enhance or counteract the inflammatory response for which our immune systems are responsible and aid in the digestion of our foods. These once overshadowed microorganisms actually play a crucial role in regulating our bodies in ways beyond belief.


It is now evident that the prospects of microbial studies are evolving in rapid and fascinating ways. Though the journey is tough in learning about these invisible forces within and all around us, Dr. Clayton and his lab pave the way for continued discovery.


There is a beauty in paying attention to the smallest of details in life, literally.


And for the microbiome, us taking the chance to unleash its beauty has made all the difference between understanding who we really are and missing out on such an opportunity.

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