Microbiota Modulation of the Gut-Lung Axis in COVID-19

Abstract

COVID-19 is an infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), and according to the World Health Organization (WHO), to date, SARS-CoV-2 has already infected more than 91.8 million people worldwide with 1,986,871 deaths. This virus affects mainly the respiratory system, but the gastrointestinal tract (GIT) is also a target, meanwhile SARS-CoV-2 was already detected in oesophagus, stomach, duodenum, rectum, and in fecal samples from COVID-19 patients. Prolonged GIT manifestations in COVID-19, mainly the diarrhea, were correlated with decreased richness and diversity of the gut microbiota, immune deregulation and delayed SARS-CoV-2 clearance. So, the bidirectional interactions between the respiratory mucosa and the gut microbiota, known as gut-lung axis, are supposed to be involved in the healthy or pathologic immune responses to SARS-CoV-2. In accordance, the intestinal dysbiosis is associated with increased mortality in other respiratory infections, due to an exacerbated inflammation and decreased regulatory or anti-inflammatory mechanisms in the lungs and in the gut, pointing to this important relationship between both mucosal compartments. Therefore, since the mucous membranes from the respiratory and gastrointestinal tracts are affected, in addition to dysbiosis and inflammation, it is plausible to assume that adjunctive therapies based on the modulation of the gut microbiota and re-establishment of eubiosis conditions could be an important therapeutic approach for constraining the harmful consequences of COVID-19. Then, in this review, we summarized studies showing the persistence of SARS-CoV-2 in the gastrointestinal system and the related digestive COVID-19 manifestations, in addition to the literature demonstrating nasopharyngeal, pulmonary and intestinal dysbiosis in COVID-19 patients. Lastly, we showed the potential beneficial role of probiotic administration in other respiratory infections, and discuss the possible role of probiotics as an adjunctive therapy in SARS-CoV-2 infection.

Oral Microbiome Dysbiosis Is Associated With Symptoms Severity and Local Immune/Inflammatory Response in COVID-19 Patients: A Cross-Sectional Study

“…Overall, the data presented here suggest a correlation between HOM dysbiosis and individual susceptibility to SARS-CoV-2 severe infection, indicating an interplay between HOM profile (including mycobiome and virome), inflammation, and mucosal IgA response. If HOM alteration is the cause or effect of severe COVID-19, it is not currently possible to distinguish, because the presence of SARS-CoV-2 in the oral cavity may impact microbiome dysbiosis ( Xiang et al, 2020 ; de Oliveira et al, 2021 ). On the other hand, connections between oral dysbiosis and post-viral complications have been reported, suggesting that improving oral health may reduce the risk of complications from COVID-19 ( Sampson et al, 2020 ), thus supporting the hypothesis of a role of dysbiosis in the virus-induced disease.…”

Diabetes and coronavirus (SARS-CoV-2): Molecular mechanism of Metformin intervention and the scientific basis of drug repurposing

“…Gut microbes such as Faecalibacterium prausnitzii , Eubacterium rectale , and several bifidobacterial species known for their immunomodulatory roles were depleted in patients with COVID-19 [ 109 ]. This dysbiosis directly correlated with COVID-19 severity and persistent infection of SARS-CoV-2 in the gut epithelium [ 110 ]. Moreover, studies identify a crucial link between the gut microbiome and lung health, coined by the term “gut–lung axis,” where gut dysbiosis was associated with ARDS development [ 111 , 112 ].…”

Probiotics for the Prevention of Acute Respiratory-Tract Infections in Older People: Systematic Review

“…The potential application of probiotics for the prevention and treatment of COVID-19 will probably be extensively investigated in the future, and several reviews also address the question of whether probiotics could be used as possible adjuvant therapy in the prophylaxis and/or alleviation of COVID-19 symptoms [66,[86][87][88]. The main basis for this possibility is that several clinical studies have reported alterations of gut microbiota/dysbiosis of COVID-19 patients [89][90][91], and it is well-known that probiotics are efficient in positively modulating the gut microbiome in many cases of dysbiosis as has been noted in systematic reviews and meta-analyses [92][93][94][95]. To date, one clinical study has addressed this question, and it concluded that support for further trials to assess the potential role of probiotics in preventing viral URTI (and possibly also COVID-19) is warranted [96].…”