Gut Microbiome Alterations in COVID-19

Since the outset of the coronavirus disease 2019 (COVID-19) pandemic, the gut microbiome in COVID-19 has garnered substantial interest, given its significant roles in human health and pathophysiology. Accumulating evidence is unveiling that the gut microbiome is broadly altered in COVID-19, including the bacterial microbiome, mycobiome, and virome.

Overall, the gut microbial ecological network is significantly weakened and becomes sparse in patients with COVID-19, together with a decrease in gut microbiome diversity. Beyond the existence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the gut microbiome of patients with COVID-19 is also characterized by enrichment of opportunistic bacteria, fungi, and eukaryotic viruses, which are also associated with disease severity and presentation. Meanwhile, a multitude of symbiotic bacteria and bacteriophages are decreased in abundance in patients with COVID-19. Such gut microbiome features persist in a significant subset of patients with COVID-19 even after disease resolution, coinciding with ‘long COVID’ (also known as post-acute sequelae of COVID-19). The broadly-altered gut microbiome is largely a consequence of SARS-CoV-2 infection and its downstream detrimental effects on the systemic host immunity and the gut milieu. The impaired host immunity and distorted gut microbial ecology, particularly loss of low-abundance beneficial bacteria and blooms of opportunistic fungi including Candida, may hinder the reassembly of the gut microbiome post COVID-19. Future investigation is necessary to fully understand the role of the gut microbiome in host immunity against SARS-CoV-2 infection, as well as the long-term effect of COVID-19 on the gut microbiome in relation to the host health after the pandemic.

Concluding remarks and perspectives

SARS-CoV-2 infection leads to complicated immunologic and pathophysiologic responses in the host. Along with the phenotypic changes in the host, the gut microbiome is broadly altered in COVID-19, including the bacterial microbiome, mycobiome, and virome. Moreover, subsequent blooms of opportunistic bacteria, fungi, and viruses under circumstances of SARS-CoV-2 infection and quiescent/overt gut inflammation in COVID-19 pose further threats to host health and gut microbiome restoration. Such expansions in certain microbial species and decreases in microbiome diversity in conjunction with the impaired host immunity may hinder re-assembly of the gut microbiome post COVID-19. Consequently, the altered gut microbiome ecology persists even after disease resolution.

Overall, the intricate microbiome ecological network in a steady state is significantly weakened in COVID-19, shifting to one predominated by COVID-19-enriched microbes. It is well-known that confounding factors such as treatment and diet can significantly affect the gut microbiome composition. However, due to the acute nature of COVID-19, controlling for these confounding factors or including treatment-naïve COVID-19 patients seems infeasible. Therefore, some of the differences between the microbiomes of COVID-19 and controls, and of those between disease stages (i.e., mild vs. severe COVID-19 cases), could be attributed to treatment regimens and/or diet.

Albeit, we observed consistent microbiome changes across studies, including decreases in the abundance of Eubaterium and SCFA-producing bacteria [12, 15, 19, 34, 35]. In addition, we observed that SARS-CoV-2 infection predominated over medications and diet in affecting the gut virome alterations in patients with COVID-19 [13]. These results together suggest that SARS-CoV-2 infection might be a crucial contributor to the gut microbiome dysbiosis in patients with COVID-19. Although studies have demonstrated that the infection of SARS-CoV-2 would lead to the altered gut microbiome, the causal relationships among the baseline gut microbiome (before infection) that regulates ACE2 expression and host immune status, infectivity/severity of SARS-CoV-2, and altered gut microbiome after infection are complicated.

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Journal Pre-proofs
Review
Gut Microbiome Alterations in COVID-19
Tao Zuo, Xiaojian Wu, Weiping Wen, Ping Lan
PII: S1672-0229(21)00206-0
DOI: https://doi.org/10.1016/j.gpb.2021.09.004
Reference: GPB 572
To appear in: Genomics, Proteomics & Bioinformatics

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