Gut and airway microbiota dysbiosis and their role in COVID-19 and long-COVID

Abstract

The gut microbiota plays a crucial role in human health and disease. Gut dysbiosis is known to be associated with increased susceptibility to respiratory diseases and modifications in the immune response and homeostasis of the lungs (the so-called gut-lung axis). Furthermore, recent studies have highlighted the possible role of dysbiosis in neurological disturbances, introducing the notion of the “gut-brain axis.” During the last 2 years, several studies have described the presence of gut dysbiosis during coronavirus disease 2019 (COVID-19) and its relationship with disease severity, SARS-CoV-2 gastrointestinal replication, and immune inflammation. Moreover, the possible persistence of gut dysbiosis after disease resolution may be linked to long-COVID syndrome and particularly to its neurological manifestations. We reviewed recent evidence on the association between dysbiosis and COVID-19, investigating the possible epidemiologic confounding factors like age, location, sex, sample size, the severity of disease, comorbidities, therapy, and vaccination status on gut and airway microbial dysbiosis in selected studies on both COVID-19 and long-COVID. Moreover, we analyzed the confounding factors strictly related to microbiota, specifically diet investigation and previous use of antibiotics/probiotics, and the methodology used to study the microbiota (α- and β-diversity parameters and relative abundance tools). Of note, only a few studies focused on longitudinal analyses, especially for long-term observation in long-COVID. Lastly, there is a lack of knowledge regarding the role of microbiota transplantation and other therapeutic approaches and their possible impact on disease progression and severity. Preliminary data seem to suggest that gut and airway dysbiosis might play a role in COVID-19 and in long-COVID neurological symptoms. Indeed, the development and interpretation of these data could have important implications for future preventive and therapeutic strategies.

The relationship between gut and nasopharyngeal microbiome composition can predict the severity of COVID-19

“…The association of then microbiota composition with these clinical variables has been widely studied [15] and it is well described that the microbiota can modulate host immunity and physiological functions [47], Consequently, the microbiota could be key in the clinical phenotype of these patients although the specific contribution of the microbiota to the progression of the infection and a poor prognosis is not yet fully understood. This study addresses for the first time the implication of nasopharyngeal and faecal microbiota in the prognosis of COVID-19.…”

“…Moreover, SARS-CoV-2 infection has been extensively reported to induce dysbiosis the in the respiratory tract and the colon [17][18][19][20], characterized by increased presence of opportunistic pathogens, including Staphylococcus, Corynebacterium and Acinetobacter bacteria [14,15], which can raise the risk of secondary infections, morbidity and mortality [16]. Thus, it is evident that there is a relevant connection between the microbiome from the respiratory and gastrointestinal tracts and the development and progression of this disease, and also the recovery processes [14,20].…”

Gut microbiota, inflammatory proteins and COVID-19: a Mendelian randomisation study

“…Researchers have found that gut microbiota affect lung health through an important crosstalk with the lungs, the “gut-lung axis” ( 30 ). Gut ecological dysregulation can lead to increased vulnerability to respiratory diseases ( 31 ). Gut-Lung axis is bi-directional; gut microbiota metabolites can affect the lungs through the bloodstream and it can also affect the gut microbiota when inflammation occurs in the lungs ( 32 ).…”

Alterations in microbiota of patients with COVID‐19: implications for therapeutic interventions

“…Dysbiosis may also play an important role in central inflammation through the gut–brain axis to mediate central symptoms. Because the recovery of intestinal dysbiosis requires a certain period of time, the related symptoms mediated by intestinal dysbiosis may continue to affect patients with COVID‐19 99,100 . Most patients with COVID‐19 have mild symptoms and recover well, but some patients develop severe COVID‐19.…”