[Preprint] Gut microbiota from patients with mild COVID-19 cause alterations in mice that resemble post-COVID syndrome, 2022, Mendes de Almeida et al

Gut microbiota from patients with mild COVID-19 cause alterations in mice that resemble post-COVID syndrome
Viviani Mendes de Almeida, Daiane F Engel, Mayra Fernanda Ricci, Clênio Silva Cruz, Icaro Santos Lopes, Daniele Almeida Alves, Mirna d’ Auriol, João Magalhães, Giuliana S. Zuccoli, Bradley Joseph Smith, Victor Corasolla Carregari, Elayne Cristina Machado, Victor M. Rocha, Toniana G. Carvalho, Larisse de Souza Barbosa Lacerda, Jordane C. Pimenta, Izabela Galvão, Mariana Aganetti Silva, Erika da Silva Rosa, Geovanni Dantas Cassali, Cristiana C. Garcia, Mauro Martins Teixeira, Leiliane Coelho, Fabiola Mara Ribeiro, Flaviano S. Martins, Rafael Simone Saia, Vivian Vasconcelos Costa, Daniel Martins-de-Souza, João T. Marques, Eric R. G. R. Aguiar, Angelica T. Vieira

Background
There is mounting evidence that SARS-CoV-2 targets tissues beyond the respiratory tract. Long-term sequelae after COVID-19 are frequent and of major concern. Prolonged virus detection in the gut has been particularly intriguing. Of note, SARS-CoV-2 infection also disturbs the gut microbiota composition, a finding linked with disease severity in patients with COVID-19. Here, we aimed to characterize the functional role of the gut microbiota in the long-term consequences of COVID-19. To this end, we characterized the gut microbiota from COVID-19 human subjects and followed the effects of human fecal transfer to germ-free mice.

Results
The gut microbiota of post-COVID subjects (up to 4 months from the initial positive test) revealed a remarkable predominance of Enterobacteriaceae strains with multidrug-resistance phenotype compared to healthy controls. After fecal transfer to germ-free mice, animals receiving samples from post-COVID subjects displayed higher lung inflammation and increased susceptibility to pulmonary infection caused by an antimicrobial resistant Klebsiella pneumoniae strain. These mice also showed poorer cognitive performance associated with increased expression of TNF-α, reduced levels of brain-derived neurotrophic factor-BDNF and postsynaptic density protein-PSD-95 in the brain, as well as alterations of several biochemical pathways. These alterations were observed in the absence of SARS-CoV-2, suggesting that alterations in the gut microbiota caused them. Consistent with this hypothesis, brain dysfunctions induced in a mouse model of coronavirus infection were partially prevented by modulation of the microbiota via treatment with the commensal probiotic bacteria Bifidobacterium longum 51A.

Conclusions
Our results show prolonged impact of SARS-CoV-2 infection in the gut microbiota that persists even after the individuals have cleared the virus. Increased Enterobacteriaceae with antimicrobial resistance phenotype were of particular concern. Moreover, microbiota transfer from post-COVID subjects induced loss of brain cognitive functions and impaired lung defense in mice. Altogether, our work emphasizes the importance of microbiota as a target for therapies to help treat post-COVID sequelae.

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Which might also be relevant in ME as we have altered gut microbiota. Needs replication, development of objective outcome measures, human studies, and investigation in similar diseases like ME, but might be interesting in the long term.

 

Published as Gut microbiota from patients with COVID-19 cause alterations in mice that resemble post-COVID symptoms (2023, Gut Microbes)