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Xiao et al. Microbiome Res Rep 2024;3:7 https://dx.doi.org/10.20517/mrr.2023.48 Page 5 of 10

[39]
infections . It is worth noting that microbial co-infection is a serious factor in COVID-19, exacerbating the
processes of the occurrence, development and prognosis of COVID-19, and the difficulties of clinical
[40]
diagnosis and treatment .

Therefore, it is essential to consider the complex interplay of factors that may impact the gut microbiota in
COVID-19 patients, including the direct impact of the virus, systemic inflammation, and treatment-related
factors.

CONSEQUENCES OF GUT MICROBIOTA DYSBIOSIS IN COVID-19 PATIENTS
A healthy gut microbiota is significantly necessary to maintain the human body’s immune homeostasis.
Dysbiosis of the microbiota caused by COVID-19 infection can disrupt host immunity in the following
[41]
ways. Butyric-producing bacteria can downregulate genes linked to SARS-CoV-2 infection . SCFAs,
including butyric acid, can promote CD8 T cell function to facilitate the clearance and depletion of the
+
[42]
influenza virus . In addition, the differentiation of Treg cells and IL-10-producing T cells is stimulated by
SCFAs binding to GPR109A, a butyrate receptor , which imparts an anti-inflammatory effect . However, a
[43]
paradox arises as SCFA-producing microbiota exhibit an inverse correlation with SARS-CoV-2 fecal
[44]
abundance . A previous study suggested that the Bacteroidetes phylum, which is reduced in severe and
critically ill patients infected by COVID-19, could activate colonic dendritic cells through the TLR4-TRIF
pathway . Lactobacillus, which was proved to be remarkably decreased in COVID-19 patients , can
[46]
[45]
produce the aryl hydrocarbon receptor (AhR) ligand-indole-3-aldehyde that promotes AhR-dependent IL22
transcription and improves resistance against mucosal inflammation . COVID-19 enrichment-induced
[47]
opportunistic pathogen Veillonella is associated with Th17 cell recruitment, neutrophil enrichment, and IL7
[48]
inflammatory phenotype activation .
The academic community widely acknowledges the potential for gut microbiota alterations to influence
[49]
susceptibility to SARS-CoV-2 . Transferring gut bacteria from patients with long COVID to healthy mice
[50]
resulted in lost cognitive functioning and impaired lung defenses in the mice . Furthermore, the altered
intestinal barrier of viral infection results in changes in the gut microbiota and its metabolites, and
translocation of intestinal bacteria to the circulation or other sites, leading to increased systemic or local
inflammation and subsequent impairment of multi-organ function . The gut microbiota, serving as a
[51]
pivotal connection among organs, is critical for maintaining the host system's equilibrium. Dysbiosis,
observed in COVID-19 patients, escalates the risk of systemic disease manifestation.

In conditions of viral enteric infection, microorganisms and damaged tissue in the body can degrade and
become a new source of nutrition, leading to a temporary oversupply of nutrition. This nutritional
oversupply induces inflammation during acute infection and potentially leads to chronic diseases like
[52]
malignancies . These insights lay the foundation for further research into the relationship between gut
[53]
microbiota alteration due to COVID-19 and the emphasized risk of developing or progressing colorectal
[54]
cancer . SCFAs regulate inflammation by macrophages in the intestine and promote the Warburg effect,
which metabolically constrains the neoplastic cells; however, fecal samples from patients with high SARS-
[55]
CoV-2 infectivity had lower abundances of SCFA-producing bacteria . A reduction in SCFA-producing
bacteria can also disrupt gut epithelial barrier integrity via IL-22 signaling and promote inflammatory
signaling through IL-18 [56,57] .

In addition, the relationship between gut microbiota and mental illness is a hot topic of current
research [58,59] . The gut-brain axis, facilitating communication between the gut and the brain, emerges as a
pivotal consideration in gut microbiota research. Numerous studies have shown that dysbiosis has been