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Coronavirus disease 2019 (COVID-19), caused by a
novel beta-coronavirus (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), has been a global
pandemic and caused more than five million deaths
worldwide until November of 2021 [1]. The primary
symptoms of COVID-19 are demonstrated in the
respiratory system, and extrapulmonary manifestations
including gastrointestinal (GI) symptoms, thrombotic
complications, and myocardial dysfunction are common
[2]. SARS-CoV-2 could invade human cells via the
angiotensin-converting enzyme 2 (ACE2) receptor,
which is highly expressed in intestines and plays an important role in maintaining gut health [3–5]. The infection of SARS-CoV-2 could impair the normal expression
of ACE2, which might result in several adverse outcomes, including GI symptoms as well as the dysbiosis
of gut microbiota [6]. Reports from multiple regions of
the world showed that 15% to 69% of COVID-19 patients had at least one GI symptom [7–10].
The microbial communities that reside in the human gut could maintain host homeostasis by providing essential functions, including immunomodulation,
nutrient metabolism, and structural protection against
pathogenic microorganisms [11–13]. Altered gut
microbiota was observed among patients with a wide
range of infectious diseases, including influenza and
other respiratory viral infections [14–17]. Recent studies also described the alterations in the gut microbial
composition of COVID-19 patients, characterized by
enrichment of opportunistic pathogens and depletion
of beneficial commensals [18–20]. In addition, three
bacterial members from the Firmicutes phylum were
positively and two beneficial species, Alistipes onderdonkii and Faecalibacterium prausnitzii were inversely
associated with COVID-19 severity [21]. However, the
potential mechanism underlying the associations
between the gut microbiome and COVID-19 severity
remains to be explored.
SARS-CoV-2 infection induces the host immune
responses to eliminate the virus, and previous evidence
suggested that aberrant immune responses were responsible for adverse outcomes and possibly other inflammations beyond COVID-19 [22, 23]. The GI tract is the
largest immunological organ in the human body and its
resident microbiota are known to modulate host immune responses [24, 25]. According to a prospective
study, the gut microbial composition was correlated with
the increase of inflammation markers, including interleukin (IL)-10, tumor necrosis factor-α, and C-reactive
protein (CRP) in COVID-19 patients [21]. Nevertheless,
data revealing the global relations between the gut
microbiome and host systemic immune response in
COVID-19 are still limited.
The microbiota-host immune interactions could be
mediated by other host factors such as gut barrier function. Intestinal epithelial cells provide a physical and biochemical barrier that segregates host tissue and bacteria
to maintain intestinal homeostasis [26]. Both virus infection and altered gut microbiota could disturb the normal
function of the gut barrier and lead to a leaky gut with
enhanced gut permeability [27], which aggravates overactivation of the host immune response [28, 29]. Thus
far, no study has characterized the role of gut barrier
dysfunction in the relationship between gut microbes
and host immune homeostasis in COVID-19 patients,
which may deepen our understanding of COVID-19
pathophysiology.
To better understand the role of gut microbiota in
COVID-19 pathogenesis, we characterized the gut
microbiota and gut barrier function among 63 COVID19 patients and 8 uninfected controls through metagenomic and metaproteomic approaches and estimated the
associations of gut microbiota with disease severity as
well as host systemic immune responses.
3 answers
-Global pandemic (5 million deaths worldwide)
-Respiratory symptoms
-Extrapulmonary manifestations (gastrointestinal symptoms, thrombotic complications, myocardial dysfunction)
-Invasion of human cells via ACE2 receptor (expressed in intestines)
-Impairment of ACE2 expression
-Adverse outcomes (GI symptoms, dysbiosis of gut microbiota)
-Gut microbiota
-Maintains host homeostasis
-Immunomodulation, nutrient metabolism, structural protection
-Altered gut microbiota in infectious diseases
-Influenza and respiratory viral infections
-Enrichment of opportunistic pathogens, depletion of beneficial commensals in COVID-19 patients
-Positive association with Firmicutes phylum, inverse association with Alistipes onderdonkii and Faecalibacterium prausnitzii
-Association with COVID-19 severity
-Host immune responses
-Elimination of virus
-Aberrant immune responses responsible for adverse outcomes and inflammations
-GI tract as the largest immunological organ
-Modulation of host immune responses by gut microbiota
-Correlation between gut microbial composition and inflammation markers (IL-10, TNF-α, CRP) in COVID-19 patients
-Limited data on global relations between gut microbiome and host systemic immune response in COVID-19
-Gut barrier function
-Maintains intestinal homeostasis
-Virus infection and altered gut microbiota disturb gut barrier function
-Leaky gut with enhanced gut permeability
-Role in relationship between gut microbes and host immune homeostasis in COVID-19 patients not characterized
-Characterization of gut microbiota and gut barrier function in COVID-19 patients and controls
-Metagenomic and metaproteomic approaches
-Associations with disease severity and host systemic immune responses
1. COVID-19
- Global pandemic
- Caused by SARS-CoV-2
- Primary symptoms in respiratory system
- Extrapulmonary manifestations (GI symptoms, thrombotic complications, myocardial dysfunction)
2. Gut Microbiota
- Maintains host homeostasis
- Altered in infectious diseases
- Specific alterations observed in COVID-19 patients
- Association with COVID-19 severity
3. Host Immune Responses
- Eliminates the virus
- Aberrant immune responses responsible for adverse outcomes
- Gut microbiota modulates immune responses
- Correlation between gut microbial composition and inflammation markers in COVID-19 patients
4. Gut Barrier Function
- Maintains intestinal homeostasis
- Disturbed by virus infection and altered gut microbiota
- Leads to leaky gut with enhanced gut permeability
- Role in relationship between gut microbiota and host immune homeostasis in COVID-19 patients
5. Research Approach
- Characterization of gut microbiota and gut barrier function
- Metagenomic and metaproteomic approaches
- Associations with disease severity and host systemic immune responses in COVID-19 patients
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