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Review
. 2022 Sep 14;11(18):5400.
doi: 10.3390/jcm11185400.

Mechanisms Leading to Gut Dysbiosis in COVID-19: Current Evidence and Uncertainties Based on Adverse Outcome Pathways

Laure-Alix Clerbaux  1 , Julija Fillipovska  2 , Amalia Muñoz  3 , Mauro Petrillo  4 , Sandra Coecke  1 , Maria-Joao Amorim  5   6 , Lucia Grenga  7
Affiliations
Review

Mechanisms Leading to Gut Dysbiosis in COVID-19: Current Evidence and Uncertainties Based on Adverse Outcome Pathways

Laure-Alix Clerbaux et al. J Clin Med. .

Abstract

Alteration in gut microbiota has been associated with COVID-19. However, the underlying mechanisms remain poorly understood. Here, we outlined three potential interconnected mechanistic pathways leading to gut dysbiosis as an adverse outcome following SARS-CoV-2 presence in the gastrointestinal tract. Evidence from the literature and current uncertainties are reported for each step of the different pathways. One pathway investigates evidence that intestinal infection by SARS-CoV-2 inducing intestinal inflammation alters the gut microbiota. Another pathway links the binding of viral S protein to angiotensin-converting enzyme 2 (ACE2) to the dysregulation of this receptor, essential in intestinal homeostasis-notably for amino acid metabolism-leading to gut dysbiosis. Additionally, SARS-CoV-2 could induce gut dysbiosis by infecting intestinal bacteria. Assessing current evidence within the Adverse Outcome Pathway framework justifies confidence in the proposed mechanisms to support disease management and permits the identification of inconsistencies and knowledge gaps to orient further research.

Keywords: ACE2 dysregulation; COVID-19; SARS-CoV-2 infection; gastrointestinal disorders; gut dysbiosis; intestinal inflammation; microbiota.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Spike proteins of SARS-CoV-2 virus binding to ACE2 receptor expressed in enterocytes mediates viral entry inducing intestinal inflammation (release of pro-inflammatory mediators and recruitment of inflammatory cells) leading to alteration of gut microbiota. Created with Biorender.com.
Figure 2
Figure 2
Virus binding to ACE2 expressed in enterocytes induces ACE2 dysregulation leading to alteration in gut microbiota. Created with Biorender.com.
Figure 3
Figure 3
SARS-CoV2 infection of gut microbial bacteria might drive alteration in the gut microbiota. Created with Biorender.com.
Figure 4
Figure 4
The three proposed pathways leading to gut dysbiosis following SARS-CoV-2 presence in the gut lumen are not mutually exclusive but might be interconnected. Created with Biorender.com.
See this image and copyright information in PMC

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