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The Connection between Gut Health, Immune Response, and COVID-19 Severity
Tuesday, February 2, 2021

As we have all heard, the gastrointestinal tract (gut) is full of numerous types of bacteria.  Some are helpful, some are harmful.  For those of us who take probiotics and/or eat fermented foods, we know that we are working to increase the good bacteria in our guts.  However, the bacteria in our guts impact more than just our digestion.  In fact, research is showing that the bacteria in our guts may play a role in the development of a variety of diseases and may also impact how our bodies respond to disease.  What’s more, some studies even suggest that different probiotics could be effective therapies for chronic diseases, such as diabetes and atherosclerosis.

The gut microbiome (meaning the mixture of different bacteria present in the gut) plays a major role in a person’s immune system and the body’s ability to respond to insults, including infections. The bacteria mix in the gut is influenced by a number of different factors, including where a person lives, diet and nutrition, age, drugs taken by the person, stress, as well as diseases the person may have.  Changes in the normal gut bacteria mixture and/or a change in how that bacteria functions causes a condition known as dysbiosis. 

Of special importance right now, the bacteria in a person’s gut may influence the clinical course of a person who contracts COVID-19.  Recent studies indicate that changes in the normal bacterial composition of the gut may lead to a dysfunctional immune response to COVID-19, resulting in severe complications.  Studies show that patients with dysbiosis are prone to an exaggerated immune response, leading to a strong inflammatory state – also known as a cytokine storm [an over reaction of the immune system that can cause inflammation, fever, swelling, etc., and even organ failure].  Even otherwise healthy people with dysbiosis may be predisposed to an atypical inflammatory response when infected with COVID-19. 

Also consider, it has been established that individuals who manifest severe COVID-19 often have two or more comorbidities, including COPD, diabetes, chronic kidney disease, heart disease, atherosclerosis, and cancer.  The development of many of these comorbidities has also been linked to gut dysbiosis. Therefore, gut dysbiosis may explain why the presence of comorbidities, which results in a dysfunctional immune response, could cause an increased susceptibility to contract COVID-19, as well as an increased susceptibility for progression to severe disease. 

It is also important to note that the COVID-19 virus itself causes gut dysbiosis, resulting in compromised immunity during the course of the virus.  This dysbiosis may, potentially, last for months after clearance of the virus and explain why some individuals have persistent symptoms or “long” COVID.  Several studies have already demonstrated that, when compared with healthy individuals, COVID-19 patients present a significantly reduced gut bacterial diversity; a higher abundancy of opportunistic bacteria; and a decrease in levels of beneficial bacteria which are known to promote a healthy immune response.  Moreover, the bacterial mix of COVID-19 patients correlates with elevated levels of inflammatory cytokines [cells that regulate immune response] and inflammatory markers when compared with the bacterial mix of healthy individuals.  Gut bacteria also influence lung health through a two directional pathway called the “gut-lung axis.” Numerous studies have reported an increase of intestinal bacterial species in the lung microbiome during COVID-19 infection, which may play an important role in the development of acute respiratory distress syndrome (ARDS), one of the main complications associated with COVID-19.

As the ongoing studies reveal new evidence, the hypothesis of gut dysbiosis leading to immune hyper-response leading to heightened inflammatory response has been gaining more and more credibility.  Gut microbiota composition might eventually be viewed as a commonly accepted predictor of COVID-19 susceptibility and severity.  Furthermore, reinforcement of beneficial gut species depleted in COVID-19 could serve as a novel treatment to lessen the risk of severe disease.

More generally, numerous studies have recently investigated how changes in gut bacteria composition affect the immune system and how that relationship may function in disease.  Scientists have recently discovered that colon cancer may evolve from an interaction between an altered gut microbiome, the immune system, and epithelial cells that line the colon.  Several studies have reported gut dysbiosis as a factor in rapid progression of insulin resistance in type 2 diabetes.  Gut dysbiosis has also been associated with the development and progression of respiratory diseases, such as asthma and COPD, and chronic kidney disease.  Furthermore, accumulating evidence has revealed that gut dysbiosis triggers both local and systemic inflammation to cause chronic inflammatory diseases, including atherosclerosis.

Additionally, drugs taken to treat some chronic diseases, such as metformin for diabetes and hypertensive and cholesterol meds for heart disease, have the capability to change the gut microbiome balance, possibly further altering immune response and increasing disease susceptibility.  Some evidence indicates that a few of these drugs may instead have a beneficial effect on the gut microbiome.  On the other hand, existing gut bacterial imbalance may also affect how these drugs are metabolized as treatments.

What are the legal implications of this evolving information about the effects of our gut bacteria?  As with our growing understanding of the roles of genetics, viruses, etc., in the development of disease, when evaluating the legal cause of an individual’s disease, debility and/or demise, we should add the status of the gut microbiome.  As our medical knowledge advances, attorneys must grow in our understanding of how we analyze the legal cause of a particular plaintiff’s injuries.  Rapidly increasing medical knowledge requires that these evaluations take a holistic approach and consider the entirety of the plaintiff’s condition.  Somewhere in the complexity of the balance of a particular individual’s make up is the explanation as to why some people are injured by a particular exposure or situation and others are not. 

Sources

Ferreira C, Viana SD, Reis F. Is Gut Microbiota Dysbiosis a Predictor of Increased Susceptibility to Poor Outcome of COVID-19 Patients? An Update Microorganisms. Dec. 28, 2020: Epub. https://www.mdpi.com/2076-2607/9/1/53

Fields H. The Gut: Where bacteria and immune system meet.
https://www.hopkinsmedicine.org/research/advancements-in-research/fundamentals/in-depth/the-gut-where-bacteria-and-immune-system-meet
Copyright Nov. 2015.  

Steinbuch Y. Intestinal bacteria may affect severity of coronavirus, researchers find. https://www.foxnews.com/health/intestinal-bacteria-coronavirus-severity-study Copyright January 12, 2021.

Yeoh YK, Zuo T, Lui GC-G, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021: Epub. https://gut.bmj.com/content/early/2021/01/04/gutjnl-2020-323020

Sircana A, Framarin L, Leone N, et al. Altered Gut Microbiota in Type 2 Diabetes: Just a Coincidence? Curr Diab Rep. 2018 Sep 13;18(10):98.

Vich Vila A, Collij V, Sanna S, Sinha T, et al. Impact of commonly used drugs on the composition and metabolic function of the gut microbiota. Nat Commun. 2020 Jan 17;11(1):362.

Balvers M, van den Born BH, Levin E, Nieuwdorp M. Impact drugs targeting cardiometabolic risk on the gut microbiota. Curr Opin Lipidol. 2021 Feb 1;32(1):38-54.

Yeh CF, Chen YH, Liu SF, Kao HL, Wu MS, Yang KC, Wu WK. Mutual Interplay of Host Immune System and Gut Microbiota in the Immunopathology of Atherosclerosis. Int J Mol Sci. 2020 Nov 19;21(22):8729.

Suganya K, Son T, Kim KW, Koo BS. Impact of gut microbiota: How it could play roles beyond the digestive system on development of cardiovascular and renal diseases. Microb Pathog. 2020 Oct 24:104583.

Chunxi L, Haiyue L, Yanxia L, Jianbing P, Jin S. The Gut Microbiota and Respiratory Diseases: New Evidence. J Immunol Res. 2020 Jul 31: Epub.

Tuteja S, Ferguson JF. Gut Microbiome and Response to Cardiovascular Drugs. Circ Genom Precis Med. 2019 Sep;12(9):421-429.

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