Mild and Severe SARS-CoV-2 Infection Induces Respiratory and Intestinal Microbiome Changes in the K18-hACE2 Transgenic Mouse Model

Seibert, Brittany; Cáceres, C. Joaquín; Cardenas-Garcia, Stivalis; Carnaccini, Silvia; Geiger, Ginger; Rajão, Daniela S.; Ottesen, Elizabeth A.; Pérez, Daniel R.

doi:10.1128/spectrum.00536-21

Cited by 24 publications

(20 citation statements)

References 77 publications

(100 reference statements)

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“…Elevated temperatures seen in few subjects. (Bushmitz et al, 2013;Hartman et al, 2020;Rockx et al, 2020;Salguero et al, 2021;Woolsey et al, (Arce and Costoya, 2021;Ejaz et al, 2020;Liu et al, 2021;Seibert et al, 2021;Winkler et al, 2020;Zheng et al, 2021) mACE2-hACE2…”

Section: Discussionmentioning

confidence: 99%

“…(Ejaz et al, 2020). Seibert et al (2021) made use of the k18-hACE2 model to better understand the effect of SARS-CoV-2 infection on lung and GI microbiome diversity, an important factor in the immune system of infected hosts. Additionally, Liu et al (2021) used this model when they reverse-engineered SARS-CoV-2 clones that could be used to further understand viral pathogenesis, as well as COVID-19 variants.…”

Section: K18-hace2 Transgenic Mouse Modelmentioning

confidence: 99%

“… Seibert et al. (2021) made use of the k18-hACE2 model to better understand the effect of SARS-CoV-2 infection on lung and GI microbiome diversity, an important factor in the immune system of infected hosts.…”

Section: Animal Models Of Covid 19mentioning

confidence: 99%

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Experimental Models of COVID-19

Caldera-Crespo

Paidas

Roy

et al. 2022

Front. Cell. Infect. Microbiol.

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COVID-19 is the most consequential pandemic of the 21st century. Since the earliest stage of the 2019-2020 epidemic, animal models have been useful in understanding the etiopathogenesis of SARS-CoV-2 infection and rapid development of vaccines/drugs to prevent, treat or eradicate SARS-CoV-2 infection. Early SARS-CoV-1 research using immortalized in-vitro cell lines have aided in understanding different cells and receptors needed for SARS-CoV-2 infection and, due to their ability to be easily manipulated, continue to broaden our understanding of COVID-19 disease in in-vivo models. The scientific community determined animal models as the most useful models which could demonstrate viral infection, replication, transmission, and spectrum of illness as seen in human populations. Until now, there have not been well-described animal models of SARS-CoV-2 infection although transgenic mouse models (i.e. mice with humanized ACE2 receptors with humanized receptors) have been proposed. Additionally, there are only limited facilities (Biosafety level 3 laboratories) available to contribute research to aid in eventually exterminating SARS-CoV-2 infection around the world. This review summarizes the most successful animal models of SARS-CoV-2 infection including studies in Non-Human Primates (NHPs) which were found to be susceptible to infection and transmitted the virus similarly to humans (e.g., Rhesus macaques, Cynomolgus, and African Green Monkeys), and animal models that do not require Biosafety level 3 laboratories (e.g., Mouse Hepatitis Virus models of COVID-19, Ferret model, Syrian Hamster model). Balancing safety, mimicking human COVID-19 and robustness of the animal model, the Murine Hepatitis Virus-1 Murine model currently represents the most optimal model for SARS-CoV-2/COVID19 research. Exploring future animal models will aid researchers/scientists in discovering the mechanisms of SARS-CoV-2 infection and in identifying therapies to prevent or treat COVID-19.

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Section: Discussionmentioning

confidence: 99%

Section: K18-hace2 Transgenic Mouse Modelmentioning

confidence: 99%

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Experimental Models of COVID-19

Caldera-Crespo

Paidas

Roy

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Microbiota–control interventions with probiotics [ 206 ] and fecal microbiota transplantation (FMT) may be effective in infectious diseases [ 207 , 208 ], but there have been reports of adverse events, and caution may be required [ 209 ], additionally, the differences in indigenous microbiota among nationalities must also be considered. Since interventional studies in humans are limited, in vitro and animal model studies may be useful for research and development [ 69 , 210 , 211 , 212 ]. HIV research includes a model of SIV infection using macaques, which has the potential to effectively assess the changes in the microbiota in disease progression and the role of the gut microbiota control in therapy effectiveness [ 213 ].…”

Section: Approaches To the Study Of The Intestinal Microbiota In Infe...mentioning

confidence: 99%

Role of Microbiota in Viral Infections and Pathological Progression

Mizutani

Ishizaka

Koga

et al. 2022

Viruses

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Viral infections are influenced by various microorganisms in the environment surrounding the target tissue, and the correlation between the type and balance of commensal microbiota is the key to establishment of the infection and pathogenicity. Some commensal microorganisms are known to resist or promote viral infection, while others are involved in pathogenicity. It is also becoming evident that the profile of the commensal microbiota under normal conditions influences the progression of viral diseases. Thus, to understand the pathogenesis underlying viral infections, it is important to elucidate the interactions among viruses, target tissues, and the surrounding environment, including the commensal microbiota, which should have different relationships with each virus. In this review, we outline the role of microorganisms in viral infections. Particularly, we focus on gaining an in-depth understanding of the correlations among viral infections, target tissues, and the surrounding environment, including the commensal microbiota and the gut virome, and discussing the impact of changes in the microbiota (dysbiosis) on the pathological progression of viral infections.

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“…However, supplementation with SCFA failed to improve disease outcome in this model ( 103 ). K-18-hACE2 transgenic mice also display alterations in the cecal microbiota, with a decrease in the families Lachnospiraceae and Oscillospiraceae and an increase in the family Akkermansiaceae, although is unclear whether these mice also exhibit changes in SCFA and other metabolites ( 104 ). Taken together, this evidence supports the idea that SARS-Cov-2 causes alterations in the gut microbiota of different animal models.…”

Section: Distal Effects Of Viral Lung Infectionmentioning

confidence: 99%

Distal Consequences of Mucosal Infections in Intestinal and Lung Inflammation

et al. 2022

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Infectious diseases are one of the leading causes of morbidity and mortality worldwide, affecting high-risk populations such as children and the elderly. Pathogens usually activate local immune responses at the site of infection, resulting in both protective and inflammatory responses, which may lead to local changes in the microbiota, metabolites, and the cytokine environment. Although some pathogens can disseminate and cause systemic disease, increasing evidence suggests that local infections can affect tissues not directly invaded. In particular, diseases occurring at distal mucosal barriers such as the lung and the intestine seem to be linked, as shown by epidemiological studies in humans. These mucosal barriers have bidirectional interactions based mainly on multiple signals derived from the microbiota, which has been termed as the gut-lung axis. However, the effects observed in such distal places are still incompletely understood. Most of the current research focuses on the systemic impact of changes in microbiota and bacterial metabolites during infection, which could further modulate immune responses at distal tissue sites. Here, we describe how the gut microbiota and associated metabolites play key roles in maintaining local homeostasis and preventing enteric infection by direct and indirect mechanisms. Subsequently, we discuss recent murine and human studies linking infectious diseases with changes occurring at distal mucosal barriers, with particular emphasis on bacterial and viral infections affecting the lung and the gastrointestinal tract. Further, we discuss the potential mechanisms by which pathogens may cause such effects, promoting either protection or susceptibility to secondary infection.

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Mild and Severe SARS-CoV-2 Infection Induces Respiratory and Intestinal Microbiome Changes in the K18-hACE2 Transgenic Mouse Model

Abstract: The COVID-19 pandemic has resulted in millions of deaths. The host’s respiratory and intestinal microbiome can affect directly or indirectly the immune system during viral infections.

Cited by 24 publications

References 77 publications

Experimental Models of COVID-19

Experimental Models of COVID-19

Role of Microbiota in Viral Infections and Pathological Progression

Distal Consequences of Mucosal Infections in Intestinal and Lung Inflammation

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