Depression and Anxiety Mitigated by Fecal Microbome Transplant

Avaneesh Kunta

Authors:  Avaneesh Kunta, Dr. Bruce Stevens, Dr. Elaine Sumners, Dr. Eric Krause, Dr. Mohan Raizada

Faculty Mentor: Dr. Bruce Stevens

College:  College of Medicine

Abstract

Anxiety disorders comprise the single most common mental illness in the U.S. Anxiety develops from a complex set of mental, genetic and physical risk factors that are correlated with medical comorbidities attributable to proinflammatory pathophysiology. Recent evidence implicates profound involvement of gut microbiota in this, and a novel concept of an impaired gut-brain bidirectional communication is emerging for anxiety and other mental disorders. In addition, our studies have shown that global overexpression of angiotensin-converting enzyme-2 (ACE2) protects mice from anxiety phenotype and that these mice have unique gut microbiota. Together, this offers a unique opportunity to address the most important question regarding the role of the gut-brain axis in anxiety: is altered gut microbiota dysbiosis responsible for anxiety disorder? This paper will provide a literature survey on the current clinical understanding of mental illnesses, such as depression and anxiety, and the importance of analyzing the gut microbiome in an effort to understand gut-brain interactions. The paper will further outline the ongoing study that is designed to exploit the impact of ACE2 and microbiota by transferring their anxiolytic benefits from donor animals to affected animals by way of fecal microbiota transplant (FMT).

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Zeeshan Malik
Zeeshan Malik (@guest_3328)
1 year ago

This is very interesting! The wide range of effects that gut microbiome has shown is eye-opening.

Avaneesh
Avaneesh (@guest_3612)
Reply to  Zeeshan Malik
1 year ago

Thank you, Zeeshan!

I hope that the results of this experiment will provide further insight into understanding the biological basis of mental illnesses and ultimately reduce the stigma surrounding such diseases.

Basil Hashimi
Basil Hashimi (@guest_4054)
1 year ago

This is very profound research that I feel the medical field is lacking in nowadays. The increased stigma against mental illness serves as a barrier in the field as it deters those suffering from mental illness from seeking help. Research like yours can do society a great favor by reducing the stigma against mental illness through exploring the potential biological basis of mental illnesses such as anxiety. If society as a whole can work towards understanding that mental illness is more than just “in your head”, and has an actual biological basis, those suffering from mental illness will be more eager to seek help. Great project and I wish you the best in the future.

Avaneesh Kunta
Avaneesh Kunta (@guest_7148)
Reply to  Basil Hashimi
1 year ago

Thank you Basil for your support!

Reducing the stigma surrounding such diseases is something that I hope will come out of this experiment. There is a long way to go to try and understand the underlying biological mechanisms of mental disease but I hope that this experiment will contribute to the first steps.

Justin Varholick
Justin Varholick (@guest_4566)
1 year ago

Hi Avaneesh, what are you planning for your control? Also, do you hypothesize that the anxiety levels in the three behavioral tests will all converge? What if they do not?

Avaneesh
Avaneesh (@guest_5664)
Reply to  Justin Varholick
1 year ago

Thank you for your question Justin,

The controls for this experiment will be wild-type mice that will undergo a fecal matter transplant from donor wild-type mice.

As for the anxiety levels, the chosen behavioral tests will be staggered so that the anxiety levels of the mice will return to baseline prior to reintroducing them to a new stress test. This protocol has been approved and conducted in the previous experiment that tested to see if ACE2 overexpressing mice were protected from anxiety. The stress tests are set-up to examine parameters both behavioral and physiological so that we will have a thorough understanding of these tests are properly inducing anxiety in the mice.

Thank you,
Avaneesh Kunta

Carina Copley
Carina Copley (@guest_5224)
1 year ago

Hey Avaneesh!
From your study, I think that the role that our gut microbiota play in our mental health is an interaction that we should be exploring a lot more in the years to come. Regarding your use of mice, I was wondering exactly how the “anxiety phenotype” is expressed in mice. I see that you used the elevated plus-maze test, open field, and light-dark box exploratory test, but I just wanted to know what exactly was the “anxiety-like behavior” that mice with the anxiety phenotype would show during these tests.

Avaneesh Kunta
Avaneesh Kunta (@guest_6214)
Reply to  Carina Copley
1 year ago

Great question Carina!

This was actually something I was also very curious about going into this experiment. With each behavioral test, we examine both physiological parameters (before and after the stressor) and behavioral parameters. For the behavioral parameters, we have cameras set up that analyze the movement of the mouse during the allotted testing time. For example, the light-dark box behavioral test puts the mouse in a dark box with a hole that lets it escape. A normal mouse would feel more confident leaving the box and exploring its surroundings while an anxious mouse would stay inside the dark box because it feels more comfortable in the confined space and is too anxious to explore its surroundings. This same behavior can be applied to all the other behavioral tests.

Thank you!
Avaneesh Kunta

Himani Gubbi
Himani Gubbi (@guest_5788)
1 year ago

Hi Avaneesh! This research is particularly interesting in considering psychological symptoms as related to physiological health, particularly through the gut microbiome. I have a few questions about the application of this research and forgive me if they have already been addressed. In translating this to human research, how can the microbiome environment of an ACE-2 knock in genotype be replicated as a human therapy? Are there plans to quantify the particular microorganisms that may be different in these ACE-2 mice versus a control to further specify the particular microflora that could cause a difference in anxiety phenotype? Thank you!

Avaneesh Kunta
Avaneesh Kunta (@guest_7116)
Reply to  Himani Gubbi
1 year ago

Great questions Himani!

From a previous experiment in Dr. Eric Krause’s lab, it was found that the ACE2 overexpressing mice had a unique microbiota profile that can be quantified through microbiome analysis. When translating to clinical studies, there are a variety of ways to replicate a similar microbiome profile into humans through techniques such as probiotic supplements or even human fecal matter transplant.

As for your second question, throughout the experiment, we have planned checkpoints to collect fecal samples from all mice so that we can run a microbiome analysis at the end of the study. We hope to see the progression over time in the microbiome flora (from antibiotic treatment to FMT to pre/post-stress test) and to use multivariable analysis to pinpoint specific microorganisms in the mice that are displaying reduced anxiety-phenotypes. We can then associate these microflorae with providing anxiolytic benefits.

Thank you!
Avaneesh Kunta