Gut microbiota from post-Covid-19 patients induces lung inflammation and brain dysfunction in mice [1]

What do we already know about this subject?

Covid-19 has wreaked havoc on a global scale, resulting in millions of confirmed cases and fatalities as of March 2023. Long-term complications of Covid-19 are pervasive, affecting even individuals with mild or asymptomatic cases. Among pathophysiological responses triggered by Sars-CoV-2 infection, several studies have linked gastrointestinal symptoms and altered gut microbiota in Covid-19 during and after the infection. On SARS-CoV-2 infection, growing evidence supports the role of gut microbiota in influencing Covid-19 severity and post-Covid effects [2]. Dysbiosis, an imbalance in the gut microbiota composition, is a critical factor in the development of various diseases. Severe Covid-19 cases have been associated with alteration of the intestinal microbiota that may persist for up to a year following the initial infection [3, 4]. However, until now, it was known that Covid-19 can alter the composition of the intestinal microbiota, but we were unaware of the causal effects that the post-Covid microbiota can have on the host’s physiology.

What are the main insights from this study?

Microbiota analysis of 72 individuals with a history of Covid-19 (post-Covid group) and 59 healthy controls showed no significant differences in gut microbiota diversity (α and β diversity) between the groups, while post-Covid subjects exhibited a higher prevalence of Enterobacteriaceae strains with drug-resistant phenotypes. A higher proportion of post-Covid individuals reported antibiotic use, likely due to Covid-19 treatment. Importantly, Klebsiella strains, associated with antimicrobial resistance (AMR), were notably increased in post-Covid gut microbiota (figure 1).

To understand the direct contribution of post-Covid microbiota to the host, fecal microbiota transplantation (FMT) was performed in germ-free mice using samples from post-Covid and control donors. Post-Covid mice exhibited lung inflammation (figure 2A).

They were also more susceptible to infection with multidrug-resistant Klebsiella pneumonia displaying a more severe lung pathology and inflammatory cell infiltration but were less efficient at clearing the bacteria. Increased Enterobacteriaceae levels in the blood of post-Covid mice suggested systemic translocation. In addition, reduced serum acetate levels were observed in post-Covid Klebsiella pneumonia-infected mice (figure 2A).

Post-Covid mice exhibited memory impairment in cognitive behavioral tests, along with increased TNF expression and decreased neuroprotective factors in the hippocampus (figure 2B). Administration of a strain probiotic to mice infected with a murine coronavirus prevented memory impairment, reduced weight loss and lung tissue inflammation.

What are the consequences in practice?

This study warns about the relationship between Covid-19 and the global burden of antimicrobial resistance. Furthermore, it highlights for the first time the causal effect of post-Covid microbiota on lung and nervous system alterations.