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.

Keywords: COVID-19; SARS-CoV-2; dysbiosis; gut-brain-axis; gut-lung-axis; long Covid; microbiome; microbiota.

Figure 1

Gut-lung axis microbiota in COVID-19. This figure shows a summary of the gut-lung axis and its alterations during COVID-19. Left: the gut microbiota taxa obligately anaerobic short-chain fatty acids (propionate and butyrate) producers and anti-inflammatory taxa, not propionate and butyrate producers. Upper: facultatively anaerobic bacteria. Right: the homeostasis of the lung microbiota, resulting from acquisition (blue arrow) and elimination (red arrow) clearance. Bottom: the most significant alterations detected in gut and lung microbiota during COVID-19. All around, the confounding factors are strictly related to Microbiota. BMI: Body Mass Index; ° indicates propionate-producing bacteria, * indicates butyrate-producing bacteria, Upward arrows “↑”: increase; Downward arrows “↓”: decrease.