How the human microbiota can influence respiratory health

Profiling the bacteria and viruses residing in the human body could help to diagnose different pathogens and develop new targeted interventions.

What is already known on this topic
Growing evidence suggests that the microbes living in the human body, collectively called microbiota, can influence human health and modulate the outcomes of infections. The composition of the communities of bacteria living in the respiratory tract has been studied in several chronic respiratory diseases, but little is known about the relationship between microbiota profiles and disease severity and progression.

What this research adds
Researchers reviewed the scientific literature on the respiratory and gut microbiota of non-infectious and infectious respiratory diseases, including COVID-19. They discuss the role of the bacteria and viruses residing in the human gut and respiratory tract as well as their interactions and link to severity of disease.

Conclusions
Profiling the bacteria and viruses residing in the human body could help to diagnose different pathogens and develop new targeted interventions. However, studies that identify bacterial biomarkers of respiratory infections are necessary before moving to investigate the causal relationship between microbes and disease.

Growing evidence suggests that the microbes living in the human body, collectively called microbiota, can influence human health and modulate the outcomes of infections. Now, researchers have reviewed the scientific literature on the changes in the respiratory and gut microbiota that occur in several respiratory diseases, including COVID-19

In a review published in Trends in Microbiology, the authors discuss the role of the bacteria and viruses residing in the human gut and respiratory tract as well as their interactions and link to severity of disease. Profiling the bacteria and viruses residing in the human body could help to diagnose different pathogens and develop new targeted interventions, they say. However, they caution, studies that identify bacterial biomarkers of respiratory infections are necessary before moving to investigate the causal relationship between microbes and disease. 

Currently, 320 viral species classified within 26 families are known to infect humans. Some of the most abundant viruses are Anelloviridae, Bunyaviridae, and Papillomaviridae, which constitute more than 40% of all human viruses. 

The main bacteria of the human gastrointestinal tract include Firmicutes and Bacteroidetes, which represent 90% of gut bacteria. The composition of the communities of gut bacteria varies in the same individual due to age, lifestyle, and other factors. Bacteria also reside in the nose, which is dominated by Propionibacterium, Staphylococcus, Bifidobacterium, Streptococcus, and Moraxella, while the oral microbiota contains mostly Prevotella, Veillonella, Haemophilus, Fusobacterium, and Neisseria.

Viruses and bacteria residing in the human body are known to interact with each other and with the host: for example, the community of viruses living in the gut shapes the gastrointestinal immune system, regulating gut inflammation.

However, to compare the microbiota of different individuals in large studies, the authors note, “it is important to understand the cause-effect relationships between the microbiota and the pathophysiology of diseases, identify differences or conserved ‘cores’ of ecological and biochemical functions along life stages in different conditions, and assess correlations beyond association.”

Microbiota profiling may be important for revealing mechanisms of infections as well as differences in the onset and progression of diseases, including COVID-19 — an infectious disease caused by the SARS-CoV-2 virus that has quickly spread across the world.

Human microbiotas

The composition of the communities of bacteria living in the respiratory tract has been studied in several chronic respiratory diseases, but little is known about the relationship between microbiota profiles and disease severity and progression. 

The upper respiratory tract, which includes the nose and mouth, is the main point of entry for pathogens. The nose microbiota of healthy adults is dominated by six types of bacteria, including Staphylococcus, Moraxella, and Haemophilus — and the alteration of this composition is thought to be a biomarker in chronic rhinosinusitis. Similarly, severe asthma appears to be related to bacteria such as Firmicutes and Actinobacteria, and an altered microbial composition characterized by high levels of Proteobacteria has been associated with increased inflammation and a more severe disease.

Infants with bronchiectasis of the lower respiratory tract — a long-term condition caused by respiratory syncytial virus — have increased abundance of Haemophilus influenzae, Streptococcus, Corynebacterium, Moraxella, and Staphylococcus aureus. Studies have also showed that respiratory infections can alter the gut microbiota: for example, mice with respiratory syncytial virus or influenza virus tend to have higher levels of Bacteroidetes and lower levels in Firmicutes in their guts.

The lung microbiota can also be altered by infections: specific bacteria are common in the airways of people with cystic fibrosis, idiopathic pulmonary fibrosis, and bronchiectasis. And the gut microbiota profile of children with cystic fibrosis is characterized by high levels of Propionibacterium, Staphylococcus, and Clostridiaceae, and low levels of Eggerthella, Eubacterium, Ruminococcus, among other bacteria.

Microbial interactions

A handful of studies have analyzed the communities of viruses living in the airways of people with respiratory diseases. In adults with chronic obstructive pulmonary disease (COPD), the prevailing viruses were rhinovirus, influenza, coronaviruses, and parainfluenza viruses. In children with recurrent acute respiratory tract infections, a type of bacteria-targeting viruses called Propionibacterium phages were particularly abundant, whereas in children with severe acute respiratory infections, researchers have detected mainly viruses such as Paramyxoviridae, Coronaviridae, and Parvoviridae.

The interactions between the communities of viruses and bacteria living in the respiratory tract can influence the development and progression of respiratory disease. That’s because viruses such as respiratory syncytial virus and rhinovirus can promote the adhesion of bacteria on the cells lining the respiratory tract, thus facilitating the growth and persistence of pathogens including H. influenzae, Streptococcus pneumoniae, and Pseudomonas aeruginosa

Gut and airway microbiotas also appear to be interconnected: changes in the composition of the community of viruses in the guts of children with cystic fibrosis is associated with an increase of Proteobacteria-associated phages and a decrease in Faecalibacterium prausnitzii-associated phages. 

Recent research has shown that Prevotella is abundant in the fecal samples of people with COVID-19, though it is still unclear if this abundance precedes the infection or is a consequence of it. Higher levels of Coprobacillus, Clostridium ramosum, and Clostridium hathewayi have been linked to an increased severity of COVID-19, whereas higher levels of F. prausnitzii have been associated with a reduced disease severity. Compared to healthy people, COVID-19 patients also have a lower diversity in their gut microbiotas and a higher abundance of opportunistic pathogens, including Rothia and Streptococcus — which in some cases have been associated with an increased susceptibility to secondary bacterial lung infections.

“We envisage that further studies on the human microbiome will continue to contribute to the understanding of COVID-19 disease phenotypes, ratifying the definitive translation of big data-based microbiomics to COVID-19 enhanced diagnostics and clinics,” the researchers say.