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

transfer between microbiota across different locations remains unclear [8,11] .

Furthermore, there were differences in the gut microbiota of patients infected by COVID-19 compared with
other pneumonia patients. These variations signify a unique microbial signature associated with COVID-19,
[6]
even in cases with similar clinical presentations . Although clinical symptoms were similar between H1N1-
infected patients and COVID-19 patients, Gu et al. observed that a remarkably higher relative abundance of
Actinomycetota and Bacillota is observed in patients infected by COVID-19 compared with 24 patients
infected by H1N1 influenza . Here, we summarize the gut microbiota dysbiosis in patients with COVID-
[12]
19 in Table 1.

Moreover, emerging studies have shed light on the functional capacity of gut microbiota. The fecal
metabolomic and proteomic profile in patients infected by COVID-19 is also illustrated in these studies.
Studies have shown impaired short-chain fatty acid (SCFA) biosynthesis in fecal samples of patients
infected by COVID-19 [6,13,14] . Increased fecal sucrose and depleted fecal glucose levels were reported in
[15]
patients infected by COVID-19 compared with other individuals without COVID-19 .
Post-COVID-19 syndrome (PCS), which includes prolonged clinical symptoms and comorbidities, is a
[16]
common occurrence among COVID-19 rehabilitation patients . Vestad et al. reported significant
differences in gut microbiota between COVID-19 rehabilitation patients and healthy adults. COVID-19
rehabilitation patients had a trend of lower relative abundance of Erysipelotrichaceae UCG-003 and higher
relative abundance of Veillonella and Flavonifractor 3 months after recovery, and these taxa were strongly
linked to persistent respiratory impairment . Another follow-up study revealed that patients with a 1-year
[17]
recovery period show gradual enrichment of butyric-producing bacteria (such as Eubacterium,
Faecalibacterium, and Bifidobacterium), accompanied by an increase in α diversity of fecal microbiota and a
lower abundance of lipopolysaccharide (LPS)-producing bacteria, such as Intestinibacter and
Prevotellaceae . Additionally, existing studies have reported that changes in the gut microbiota may persist
[18]
[19]
for more than a year after recovery from COVID-19 .
POTENTIAL MECHANISMS FOR GUT DYSBIOSIS IN COVID-19 PATIENTS
The importance of the gut-lung axis has gained increasing attention with the in-depth study of COVID-19.
This axis orchestrates an intricate connection facilitated by the lymphatic system and blood circulation,
ferrying immune cell mediators, cytokines, microbial fragments or products (peptidoglycan, endotoxins,
proteins, SCFA, and hormones between these two vital systems) . Although respiratory viral infection does
[20]
not directly cause changes in the gut microbiota, lung inflammation can elicit systemic inflammatory signals
and initiate local inflammatory responses in the gut, which appears to contribute to intestinal injury . In
[21]
addition, some evidence suggests that other viral infections in the lungs may affect the gut microbiota
through the gut-lung axis by immune mediation. For example, influenza infection altered the intestinal
microbiota composition, which was mediated by IFN-γ produced by lung-derived CCR9 CD4 T cells
+
+
[20]
recruited into the small intestine . Respiratory syncytial virus (RSV) infection reduced host food
consumption and altered gut microbiota by stimulating the proliferation of CD8 T cells secreting IL-6 and
+
TNF-α . Invasion of SARS-CoV-2 into the lungs could damage tissue and cells and activate strong pro-
[22]
inflammatory pathways characterized by upregulation of NF-κB and TNF pathways to induce the intense
[23]
cytokine storm , while activated systemic and intestinal inflammation may be responsible for changes in
[24]
the gut microbiota . Briefly, invasion by SARS-CoV-2 into the lungs incites tissue damage to some extent
and robust pro-inflammatory responses, potentially triggering cascading changes in gut microbiota through
systemic and intestinal inflammation.