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[60]
linked to mental illnesses such as depression and anxiety, disrupting the gut-brain axis . Ghannoum et al.
reported that altered intestinal flora in the multiple dimensions of the gut-brain axis had a negative impact
on the body, including excessive activation of the hypothalamic-pituitary-adrenal (HPA) axis,
neural circuits, and the level of neurotransmitters. Eventually, depression and anxiety result from
these changes . Nakov et al. reported an increased prevalence of gastrointestinal symptoms during the
[61]
[62]
COVID-19 lockdown . They found that these symptoms were linked to dysfunction of the gut-
brain axis, thereby causing alterations in the neuroimmune and endocrine systems and promoting the
negative development of depression and anxiety. A long-term prospective study confirmed that
neuropsychiatric symptoms were associated with enteric pathogens, including Clostridium innocuum
and Actinomyces naeslundii, in the long-term complications of COVID-19 . Collectively, changes in
[63]
the gut microbiome and microbes that produce specific metabolites, such as butyrate, may
contribute through the gut-brain axis to neurological and psychiatric symptoms as well as GI symptoms
in COVID-19 patients . The possible mechanism of dysbiosis caused by SARS-CoV-2 infection on host
[59]
immunity and mental health is illuminated in Figure 1.

The intricate interplay between SARS-CoV-2, the gut microbiota, and its implications for immunity, disease
susceptibility, and mental health unfolds a multifaceted narrative. Exploring these connections offers a
promising avenue for advancing our comprehension of COVID-19’s profound effects.

CONCLUDING REMARKS AND PROSPECTS
COVID-19 has demonstrated a notable impact on the intricate composition and functioning of the gut
microbiota. Studies have shown differences in fecal microbial composition between healthy individuals and
COVID-19 patients, with an enrichment of bacteremia-associated microbial communities and a reduction
in beneficial commensals. The severity of COVID-19 has been found to correlate with specific bacterial
abundances, thereby underscoring the intricate relationship between microbial composition and disease
severity. Additionally, COVID-19 patients’ fecal fungi have shown remarkable heterogeneity, further
accentuating the complex nature of gut microbiota response. The ripple effects of COVID-19 transcend the
gut microbiota alone, influencing the composition of both respiratory and oral microbiota. Additionally,
individuals afflicted by COVID-19 exhibit a gut microbiota profile distinct from that of patients with other
forms of pneumonia, highlighting the unique microbial interactions associated with this viral infection. The
dysbiosis of the gut microbiota in COVID-19 patients is thought to be influenced by various factors,
including the gut-lung axis, direct infection of the gastrointestinal tract by SARS-CoV-2, and critical illness
interventions such as antibiotic use and mechanical ventilation. This intricate interplay contributes to an
altered immune response and heightened susceptibility to secondary infections. It has been observed that
alterations in carbohydrate, lipid, and amino acid metabolism of the gut microbiota are associated with
COVID-19. Post-COVID-19 syndrome, also known as long COVID, can also impact the gut microbiota,
with persistent changes observed even after recovery. The repercussions of gut microbiota dysbiosis in the
context of COVID-19 are profound. Host immunity is compromised, inflammation escalates, and the risk
of systemic diseases amplifies. An ominous link emerges between dysbiosis and the potential for colorectal
cancer development or progression. Beyond the physiological realm, the perturbations in the gut-brain axis
provoke mood disorders such as depression and anxiety.

In outlook, further research is needed to understand the mechanisms underlying the gut microbiota shifts in
COVID-19 patients and their implications for disease severity and long-term outcomes. This knowledge
holds the potential to not only illuminate the relationship between microbial composition and disease
severity but also to offer insights for innovative therapeutic strategies. Probing the composition of the
microbiota and its metabolites in the context of an emerging infectious disease may unveil new biomarkers
and new therapeutic targets. The growth of this field is evident through milestones achieved during the