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 alterations in gut microbiota

A team of scientists from Brazil recently highlighted the importance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced gut microbiota alterations in triggering symptoms of post-coronavirus disease 2019 (COVID-19 ).

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

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


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen responsible for COVID-19, is known to infect a variety of organs beyond the respiratory tract. The most important is infection of the gastrointestinal tract, which causes a considerable alteration in the composition and diversity of the intestinal microbiota. Studies in COVID-19 patients have established an association between SARS-CoV-2-induced gut microbiota alteration and COVID-19 severity.

In the present study, scientists investigated the involvement of altered gut microbiota in triggering post-covid symptoms.

study design

The study was conducted on a total of 72 post-COVID patients and 59 healthy people. Self-collected fecal samples were obtained from participants for analysis of gut microbiota composition and diversity. Samples from COVID-19 patients were collected an average of 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 triggering post-COVID symptoms, fecal samples taken from participants were transplanted into germ-free mice.

Important observations

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

Antimicrobial resistant bacteria

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

The results revealed a significantly higher level of multidrug resistance Enterobacteriaceae strains in the gut microbiota of COVID-19 patients compared to that of healthy individuals. A difference in resistance to β-lactams and penicillin antibiotics has been observed between COVID-19 patients and healthy individuals. Additionally, an increased level of Klebsiella and a reduced level of antimicrobial resistance Escherichia have been observed in the gut microbiota of COVID-19 patients.

Intestinal homeostasis

Selected biomarkers of gut integrity and systemic inflammation have been estimated to determine the impact of SARS-CoV-2 infection on overall gut homeostasis.

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

Taken together, these results suggest that SARS-CoV-2 infection induces epithelial damage; however, it is not associated with higher systemic inflammation.

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

Transplantation of post-COVID gut microbiota in mice did not cause any significant alteration of the intestinal tract. However, the lung has been identified as the most affected organ. Specifically, an increased level of lung inflammation was observed in mice that received gut microbiota from COVID-19 patients.

Importantly, no traces of SARS-CoV-2 RNA were detected in lung tissue, which is consistent with the absence of the virus in fecal samples. Thus, these results confirm that the alteration of the intestinal microbiota due to a viral infection can directly induce lung inflammation even in the absence of the virus.

Additionally, the results revealed that transplantation of post-COVID gut microbiota can make mice more susceptible to lung infections caused by antimicrobial resistant microbiota. Klebsiella pneumoniae stump.

Regarding changes in 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 alpha (TNF-alpha) have been observed after COVID-19 gut microbiota transplantation.

Additionally, a significant impact of post-COVID gut microbiota has been observed on multiple biological pathways important for normal neurological functions. These changes were associated with lower cognitive performance in mice.

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

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

Significance of the study

The study found that altered gut microbiota caused by SARS-CoV-2 infection may play a role in the development of long-term COVID-19-related symptoms even after viral clearance.

*Important Notice

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

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