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Page 4 of 10 Xiao et al. Microbiome Res Rep 2024;3:7 https://dx.doi.org/10.20517/mrr.2023.48

Table 1. The dysbiosis of gut microbiota in subjects infected with SARS-CoV-2
[8]
Wu et al. 2021 Enriched Granulicatella, Rothia mucilaginosa
[9]
He et al. 2021 Enriched Bacteroides coprophilus, Bacteroides coprocola, Bacteroides graminisolvens, Bacteroides uniformis
Depleted Lachnospiraceae, Ruminococcus, Butyrivibrio, Dorea, Eubacterium
Zuo et al. 2020 [6] Depleted Faecalibacterium prausnitzii, Lachnospiraceae bacterium 5_1_63FAA, Eubacterium rectale, Ruminococcus obeum, Dorea
formicigenerans
Zuo et al. 2020 [10] Enriched Candida albicans, Candida auris, Aspergillus flavus, Aspergillus niger
Shen et al. 2022 [11] Enriched Enterococcus, Candida
Depleted Streptococcus, Actinomyces, Atopobium, Bacteroides
[12]
Gu et al. 2020 Enriched Actinomycetota, Bacillota
[13]
Zhang et al. 2021 Enriched Bifidobacterium adolescentis, Ruminococcus bromii, F prausnitzii, Bacteroides ovatus, Bacteroides dorei, Bacteroides
thetaiotaomicron
Lv et al. 2021 [14] Enriched Streptococcus
Depleted Peptostreptococcaceae, Penicillium steckii, Aspergillus rugulosus
SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2.

Significantly, mounting evidence points towards direct infection of the gastrointestinal tract by
SARS-CoV-2. A single-cell RNA sequencing showed that ACE2 and transmembrane protease serine 2
(TMPRSS2) were highly expressed in gastrointestinal epithelial cells [25,26] . They were crucial for the entry of
SARS-CoV-2 into the host cells, and their distribution determined the virus development [27,28] . More
conclusive evidence of the correlation between COVID-19 infections and pathological changes in
gastrointestinal systems is the large proportion of positive fecal samples for viral RNA in patients infected
by COVID-19 . Furthermore, SARS-CoV-2 is often found in fecal samples during the post-symptom stage,
[29]
[30]
even when throat swabs are negative . Multiple histopathological examinations have also confirmed that
SARS-CoV-2 presents gastrointestinal tropism. Coronavirus-like particles have been found in
gastrointestinal tissues, and gastrointestinal mucosa has shown varying degrees of degeneration, necrosis,
and shedding . In studies of organoids and animal models (rhesus monkeys), the virus could infect the
[31]
gastrointestinal tract [32,33] . Once the virus reaches the epithelial cells of the intestine, the cells will be bound to
it via ACE-2, which can cause the release of chemokines and cytokines. Subsequently, the development of
an inflammatory cascade in the intestine is characterized by the infiltration of macrophages, neutrophils,
and T cells . Another theory shows that SARS-CoV-2 disease downregulates ACE2, resulting in decreased
[34]
activation of the mammalian target of rapamycin (mTOR) and increased autophagy, resulting in intestinal
[35]
dysbiosis, diarrhea, and other sympotoms . Recent studies indicate that specific microbial species such as
Bacteroides dorei, Bacteroides thetaiotaomicron, Bacteroides massiliensis, and Bacteroides ovatus exhibit
[36]
correlations with ACE2 expression and viral load, linking them to COVID-19 pathogenesis .

The critical illness phase of COVID-19 is marked by a confluence of factors, including antibiotic usage,
mechanical ventilation, diet shifts, emotional stress, and inflammatory responses, which can all perturb the
delicate microbiome balance. In sicker patients, they often require prolonged mechanical ventilation and
treatment with invasive catheters. These treatments increase susceptibility to secondary infections with
m u l t i d r u g - r e s i s t a n t p a t h o g e n s s u c h a s A c i n e t o b a c t e r baumannii, s c h e r i c h i a coli, n d
E
a
Pseudomonas aeruginosa . In a study among the 99 cases of 2019 SARS-CoV-2 in Wuhan, the co-infecting
[37]
[38]
pathogens include Acinetobacter baumannii, Klebsiella pneumoniae, and many others . The relative
abundance of these species in the intestines of patients infected by COVID-19 is higher than that of healthy
individuals. The infection of these fungi has also increased the number of patients admitted to Intensive
Care Unit (ICU) facilities and antibiotic treatments. Research suggests that about half of the deaths of
hospitalized patients infected by COVID-19 are attributable to multidrug-resistant bacteria and fungus