The lung–gut axis during viral respiratory infections: the impact of gut dysbiosis on secondary disease outcomes

Abstract

Bacteria that colonize the human gastrointestinal tract are essential for good health. The gut microbiota has a critical role in pulmonary immunity and host’s defense against viral respiratory infections. The gut microbiota’s composition and function can be profoundly affected in many disease settings, including acute infections, and these changes can aggravate the severity of the disease. Here, we discuss mechanisms by which the gut microbiota arms the lung to control viral respiratory infections. We summarize the impact of viral respiratory infections on the gut microbiota and discuss the potential mechanisms leading to alterations of gut microbiota’s composition and functions. We also discuss the effects of gut microbial imbalance on disease outcomes, including gastrointestinal disorders and secondary bacterial infections. Lastly, we discuss the potential role of the lung–gut axis in coronavirus disease 2019.

Breast Milk and COVID-19: From Conventional Data to “Omics” Technologies to Investigate Changes Occurring in SARS-CoV-2 Positive Mothers

“…We speculate that the dysbiosis in pregnant women affected by COVID-19 could compromise the translocation of good bacteria from the mother’s gut to BM, impairing the immune system development of the infant. Much has been said about the impact of an altered translocation of bacteria from the gut to the lung in cases of severe dysbiosis, of that “more gut in the lung” able to worsen the respiratory course of a viral disease including SARS-CoV-2 [ 62 , 103 , 104 , 105 , 106 ]. In our topic, the “less gut in the mammary gland” is likely to have more relevance than the “more gut”, although this can be also present and ready to fill the niches of the “less gut”.…”

The Role of Dysbiosis in Critically Ill Patients With COVID-19 and Acute Respiratory Distress Syndrome

“…Moreover, mechanical ventilation, decreased bowel transit time, reduced oxygenation, multiple antibiotic usage, sedatives, analgesics, muscle relaxants, gastric protectors, and abnormal nutritional intake may affect the composition of microbiota, which may increase the risk of dysbiosis and inflammation (15)(16)(17). Mice treated with broad spectrum or targeted antibiotics impaired their response to systemic and respiratory infections (18). Most prominent among these are gram-negative bacteria (e.g., Proteobacteria), which can lead to severe gut-lung dysbiosis (9,19).…”

“…The gut microbiota regulates the function of the immune system and cellular homeostasis of both gut and lung tissues due to antimicrobial peptides and metabolites derived from intestinal commensals (18,31). The enteric nervous system is composed of the myenteric plexuses, which control fluid movement and intestinal motility; and is influenced by the activation pattern recognition receptors (PRRs), especially tolllike receptors (TLRs) which recognize pathogens (32).…”

“…Additionally, the alteration in the secretion of mucin by goblet cells can lead to impaired mucus layer, increasing susceptibility to increased gut permeability (35). Dysbiosis results in diminished production of microbial-associated molecular patterns including TLRs and nucleotide oligomerization domain (NOD)-like agonists and microbial metabolites such as SCFAs, thus reducing antibacterial pulmonary immunity (18). Hence, by altering the gut immune homeostasis, respiratory viral superinfection may occur.…”

“…Desaminotyrosine implements type I IFN signaling of lungs' phagocytes by promoting genes transcription (45). Similarly, SCFAs result important in priming the pulmonary immune innate system (18,31). The subsequent inflammatory response can promote and encourage local inflammation followed by endothelial and epithelial injury (Figure 1).…”