Study: Gut microbiota from patients with mild COVID-19 cause alterations in mice that resemble post-COVID syndrome. Image Credit: ART-ur/Shutterstock

Study links post-COVID symptoms to changes in gut microbiota

A team of scientists from Brazil recently highlighted the importance of changes in the gut flora caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in causing symptoms of post-coronavirus disease 2019 (COVID-19).

Study: Gut microbiota from patients with mild COVID-19 cause changes in mice resembling post-COVID syndrome† Image credit: ART-ur/Shutterstock

The study is currently available on the Research Square* preprint server.

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is known to infect a variety of organs outside the respiratory tract. The most prominent is the infection of the gastrointestinal tract, which causes significant changes in the composition and diversity of the gut microbiota. Studies conducted on COVID-19 patients have shown an association between SARS-CoV-2-induced changes in the gut microbiota and the severity of COVID-19.

In the current study, the scientists investigated the involvement of changes in the gut microbiota in triggering post-Covid symptoms

Study design

The study was conducted in a total of 72 post-COVID patients and 59 healthy subjects. The self-collected fecal samples were obtained from the participants for the analysis of gut microbiota composition and diversity. The samples from the COVID-19 patients were collected on average 2 months after SARS-CoV-2 infection. At the time of collection, all fecal samples were negative for SARS-CoV-2.

To determine the functional role of SARS-CoV-2 altered gut microbiota in causing post-COVID symptoms, the fecal samples collected from the participants were transplanted into germ-free mice.

Important comments

The analysis of fecal samples revealed no significant differences in the composition and diversity of the gut microbiota between the COVID-19 patients and healthy individuals. However, the estimate of metabolites derived from the gut microbiota in the samples revealed lower levels of acetate and butyrate in COVID-19 patients compared to those in healthy individuals. These findings indicate that SARS-CoV-2 infection alters gut microbiota metabolism.

Antimicrobial resistant bacteria

To investigate the prevalence of antimicrobial resistant bacteria in fecal samples, Enterobacteriaceae family was selected for the analysis because these Gram-negative bacteria are known to transfer antimicrobial resistance genes of clinical importance.

The findings revealed a significantly higher level of multidrug resistant Enterobacteria strains in the gut microbiota of COVID-19 patients compared to those in healthy individuals. A difference in the resistance to -lactams and penicillin antibiotics was observed between COVID-19 patients and healthy individuals. In addition, an increased level of Klebsiella and a reduced level of antimicrobial resistance Escherichia were observed in the gut microbiota of COVID-19 patients.

Intestinal Homeostasis

Certain biomarkers of intestinal integrity and systemic inflammation were estimated to determine the impact of SARS-CoV-2 infection on overall intestinal homeostasis.

The findings revealed no significant difference in bacterial translocation from the gut between COVID-19 patients and healthy subjects. Similarly, no difference in blood levels of pro-inflammatory mediators was observed between the groups. However, a relatively lower level of anti-inflammatory cytokine interleukin 10 (IL-10) and a higher level of intestinal epithelial damage were observed in COVID-19 patients.

Overall, these findings suggest that SARS-CoV-2 infection causes epithelial damage; however, it is not associated with higher systemic inflammation.

Post-COVID gut microbiome-induced changes in germ-free mice

The transplantation of post-COVID gut microbiota into the mice caused no significant changes in the gut. However, the lung was identified as the most affected organ. Specifically, an increased level of pneumonia was observed in mice fed the gut flora of COVID-19 patients.

Importantly, no trace of SARS-CoV-2 RNA was detected in the lung tissues, which is consistent with the absence of the virus in fecal samples. These findings thus confirm that the alteration of the gut microbiota as a result of a viral infection can directly cause pneumonia, even in the absence of the virus.

In addition, the findings revealed that the transplantation of post-COVID gut microbiota may predispose the mice to lung infection caused by the antimicrobial resistant Klebsiella pneumoniae deformation.

With regard to changes in the mouse brain, decreased levels of neuroprotective factors, including brain-derived neurotrophic factor (BDNF) and postsynaptic density protein (PSD-95), and increased expression of tumor necrosis factor-alpha (TNF-alpha) were observed after postsynaptic density proteins (PSD-95). -COVID gut microbiota transplantation.

In addition, a significant impact of the post-COVID gut microbiota was observed on multiple biological pathways important for normal neurological functions. These changes were associated with decreased cognitive performance in mice.

For further confirmation, a mouse model of a beta-coronavirus infection was used in the study. These mice also showed cognitive impairment due to viral infection.

The mice were first pretreated with the probiotic bacteria Bifidobacterium longum 5 and then subjected to a coronavirus infection. The findings revealed that the probiotic-mediated modulation of the gut microbiota can prevent cognitive impairment associated with a viral infection.

Study meaning

The study revealed that the alteration of the gut microbiota caused by SARS-CoV-2 infection could play a role in developing long-lasting COVID-19-related symptoms even after viral clearance.

*Important announcement

Research Square publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered conclusive, should guide clinical practice/health-related behavior or be treated as established information.

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