The findings, published in Science Immunology, suggest that leveraging gut-lung interactions could offer new ways to prevent or reduce severe complications from respiratory viral infections.

One reason people get secondary infections after flu is that the virus damages lung immune cells called alveolar macrophages (AMs). SFB can help AMs stay strong during viral infections, but it’s unknown whether these microbes protect against secondary infections and how they might do so.

Researchers led by Vu Ngo at Georgia State University in Atlanta studied whether SFB protect mice from deadly bacterial infections after flu.

Boosting immunity

The team compared mice with and without SFB in their gut. Animals without SFB lost a lot of AMs and had severe lung infections after flu. In contrast, mice with SFB had strong AMs and showed much less lung damage and fewer bacteria. But when the researchers removed AM cells, even mice with SFB became vulnerable. 

Scientists have known that mice typically acquire SFB from their mothers. Compared to pups of mice without SFB, those of mice with SFB had healthier lungs, fewer bacteria, and better survival after flu and bacterial exposure, and this protection lasted for at least four generations. 

Further experiments showed that SFB work by reprogramming the lung’s AMs to resist flu-induced damage and remain effective at killing bacteria, rather than by bringing new immune cells into the lungs. The microbes also boost antibacterial activity in immune cells throughout the body.

Transferring protection

Next, the researchers found that AMs from mice without SFB lost function in an inflamed environment, but if they were placed in the lungs of mice with SFB, they regained their antibacterial activity. 

Rather than acting only by reducing harmful inflammatory signals, SFB change AMs at the genetic and metabolic level, boosting their ability to kill bacteria, produce immune helpers, and maintain energy. Transplanting AMs from SFB-colonized mice into mice without SFB transferred protection, the researchers found.

“We speculate that defining and subsequently harnessing the mechanism by which SFB colonization reprograms AM will lead to new strategies to mitigate the [respiratory viral infection] induced disease burden,” the authors say.

The findings, published in Cell Host & Microbe, suggest that the composition of the lung microbiota is shaped by different factors and can influence pneumonia progression and treatment outcomes.

Scientists have known that pneumonia involves changes in the lung microbiota and is often associated with microbial imbalance rather than a single pathogen. However, how distinct lung microbiota “states” form, how stable they are over time, and how they relate to treatment outcomes is unclear.

To address this question, Jack Sumner at Northwestern University in Evanston, Illinois, and his colleagues analyzed the lung microbiota in critically ill patients with and without pneumonia.

Microbial fingerprint

Between 2018 and 2020, the researchers followed 248 people on breathing machines who were suspected of having pneumonia, collecting fluid samples from their lungs to study infections in detail. Doctors classified their conditions into community-acquired, hospital-acquired, or ventilator-associated pneumonia, and most cases were caused by bacteria. 

By analyzing the patients’ lung microbiota, the researchers found that the type of pneumonia was linked to differences in which microbes were present in the lungs and how the patient’s immune cells behaved. 

Pneumonia was linked to shifts in certain bacteria and microbial genes, including lower levels of some normally present microbes and higher levels of others, especially Staphylococcus species, which are often linked to infection and antibiotic resistance. About 36 to 46% of pneumonia samples had disrupted lung microbiotas.

Treatment outcomes

The researchers also found that critically ill patients tend to have a lung microbiota that fall into four main groups, or “pneumotypes”: skin-like, mixed, Staphylococcus-dominated, and oral-like. Each pneumotype had distinct levels of diversity, dominant bacteria, and traits such as antibiotic resistance. 

Oral-like and Staphylococcus-dominated pneumotypes had the highest bacterial levels and greatest immune activation, while skin-like pneumotypes showed the lowest disruption. The oral-like pneumotype was associated with successful pneumonia treatment and recovery, while the skin-like pneumotype was linked to worse outcomes.

“We show that host and microbiota landscapes change in unison with clinical phenotypes and that microbiota state dynamics reflect pneumonia progression,” the authors say. “We suggest that distinct pathways of lung microbial community succession mediate pneumonia progression.”

The findings, published in mBio, highlight the importance of early-life gut microbes in shaping lung health and add to evidence that microbiota composition can influence asthma risk.

Previous studies have shown that babies with less diverse gut microbiota are more likely to develop asthma and allergies, but it’s unclear which bacteria influence asthma risk and how they affect the immune system.

Ivon Moya Uribe at Michigan State University and her colleagues set out to investigate how gut microbes affect asthma development by analyzing stool samples from 60 three-month-old infants. 

Lung function

Infants with higher levels of bacteria such as Escherichia coli-Shigella and Bifidobacterium were more likely to develop eczema by age 1-3 years, while those with more Bacteroides bacteria were less likely to have eczema. Eczema is a condition that typically begins in infancy, followed by food allergies, allergic rhinitis, and asthma.

Next, the researchers transplanted gut microbes from the two groups of infants—those with high levels of eczema-related bacteria and those with protective bacteria—into germ-free mice.

Mice that received human-derived microbiotas had high levels of pro-inflammatory and allergy-exacerbating bacteria. When exposed to allergens such as dust mites, these mice had high levels of immune molecules associated with allergic responses and showed worse lung function, including increased airway stiffness, compared to animals with a typical mouse microbiota. 

Unclear mechanisms

Although the presence of specific bacteria—such as pro-inflammatory microbes—appeared to impair lung function, the researchers found no differences in lung function or allergic airway responses between mice that received the microbiota from infants with high levels of eczema-related bacteria and those that received the microbiota from infants with protective bacteria.

Even microbes thought to be protective caused alterations in the mice’s lung function, the researchers found. These results, they say, reject the hypothesis that one microbiota would result in less severe allergic reactions.

The findings, the authors add, suggest that gut microbes alone may affect lung function and airway resistance, but further research is needed to clarify the mechanisms behind these effects.

The findings, published in Science Translational Medicine, suggest that targeting E. lenta or boosting neutrophil function may lead to new treatment strategies for bronchiectasis and related lung diseases.

Scientists have known that infection with Pseudomonas aeruginosa is a major cause of worsening symptoms of bronchiectasis. But while treatments that target Pseudomonas infections can help patients, other factors, including gut bacteria and the immune system, may contribute to the disease. 

To explore the link between the gut microbiota and bronchiectasis, researchers led by Le-Le Wang at Tongji University in Shanghai, China, analyzed blood, stool and other body samples from 41 people with the condition and 29 healthy individuals. The team also performed fecal microbiota transplants in mice.

Worsen infection

Mice first received antibiotics to clear their gut bacteria, then they were given fecal samples from either people with bronchiectasis or healthy donors before being infected with Pseudomonas aeruginosa in their lungs. 

Animals receiving stool from bronchiectasis patient showed worse lung infections, more lung damage and stronger immune responses than those receiving stool from healthy donors. This finding suggests that gut bacteria can worsen lung infections in bronchiectasis, the researchers say.

People with bronchiectasis had more harmful bacteria, especially Eggerthella lenta, in their guts. The amount of E. lenta was higher in patients with more severe disease and was associated with increased Pseudomonas aeruginosa in the lungs.

Immune cells

To test the idea that E. lenta could worsen infections, the researchers gave the bacterium to mice before infecting them with P. aeruginosa. These mice had worse lung damage, more bacteria and higher inflammation compared to animals that weren’t given E. lenta. 

Further experiments showed that E. lenta produces TUDCA, a compound that weakens the function of immune cells called neutrophils, making lung infections worse. However, treating neutrophils with metformin restored their bacterial-killing ability, the researchers found.

The findings offer evidence of a link between the gut and the lungs, but more research is needed to understand how E. lenta produces TUDCA and how metformin contributes to treating infections, the authors say.

The findings, published in mBio, suggest that delayed microbiota maturation in infants with cystic fibrosis could contribute to disease complications. “Our study builds toward microbiota-targeted therapy to restore healthy microbiota dynamics in infants with [cystic fibrosis],” the authors say.

Scientists have known that the gut microbiota develops from birth and stabilizes by age three to five, with disruptions, such as those seen in cystic fibrosis, leading to immune and digestive issues. In people with cystic fibrosis, the gut microbiota develops more slowly, and understanding these differences may help create therapies to improve the microbial makeup of people with the condition.

Adrian Verster at Dartmouth College in Hanover, New Hampshire, and his colleagues set out to examine the gut microbiota of 40 infants with cystic fibrosis and compare the results with data from thousands of infants with or without the condition.

Maturation delay

Compared with infants without cystic fibrosis, those with the condition showed differences in their gut microbiotas, including lower levels of Bacteroidota and higher abundance of Pseudomonadota.

In their first year of life, babies with cystic fibrosis could be divided in two distinct groups based on the presence or absence of Bacteroides, but all remained different from infants without cystic fibrosis, mainly due to differences in Bifidobacteria bifidum, Phoecicola vulgatus and E. coli levels.

Babies with cystic fibrosis also showed delays in gut microbiota development compared to healthy infants, with altered bacterial composition, including high Enterobacteriaceae levels and low levels of beneficial bacteria such as Faecalibacterium prausnitzii. 

Transitional state

The gut microbiotas of infants with cystic fibrosis had an increased presence of oral bacteria and fungi, such as Saccharomyces and Candida, which have been linked to inflammation, the researchers found.

The team also used machine learning models to predict microbiota age based on gut bacteria. In healthy infants, specific bacterial species indicated microbiota development across different populations, making these species potential biomarkers for gut maturation.

The findings suggest that infants with cystic fibrosis have a gut microbiota that remains in a transitional state rather than progressing to a stable adult-like microbiota by age three.

Future research, the authors say, should explore interventions to support microbiota development in people with cystic fibrosis.

The findings, published in Cell, suggest that while T. musculis can worsen asthma, it might also help the body fight off harmful microbes, offering potential for new treatments targeting the immune system.

Previous studies have shown that the gut microbiota can influence asthma and other inflammatory diseases. However, the exact microbial species and mechanisms involved remain unclear. 

Kyle Burrows at the University of Toronto in Canada and his colleagues studied mice that had been colonized with T. musculis to examine its effects on immune responses in the lungs.

Fighting off infection

Colonization with T. musculis triggered immune responses that began in the gut but affected also the lungs. Central to this process were a type of immune cells that normally reside in the gut. In the presence of T. musculis, these cells migrated to the lungs, where they stimulated the activation of immune cells linked to allergic inflammation as well as the production of inflammatory molecules.

The increase in inflammatory molecules worsened asthma symptoms in mice, triggering airway inflammation and making breathing more difficult. However, this immune response also offered protection against infection with Mycobacterium tuberculosis, the bacterium responsible for tuberculosis.

The results suggest that T. musculis promotes long-lasting immune changes, creating what researchers call a “gut-lung immune axis.”

Personalized treatments

Next, the team looked at the fluid produced in the lungs and airways of people with severe asthma. There, they found traces of protozoan DNA, including species related to T. musculis. While the exact role of these microorganisms in people with asthma remains unclear, the findings points to a potential link between colonization with T. musculis and a subset of asthma cases, the researchers say.

Targeting immune pathways activated by T. musculis could thus pave the way for personalized treatments for respiratory diseases, for example therapies to manage airway inflammation or to boost immunity against tuberculosis, the authors say. 

“These findings demonstrate that a commensal protozoan tunes pulmonary immunity via a gut-operated lung immune network, promoting both beneficial and detrimental disease outcomes in response to environmental airway allergens and pulmonary infections.”

The findings, published in Cell Reports Medicine, suggest that the microbial communities inhabiting an infant’s nose and throat can play a role in the severity of RSV infections. 

“During RSV infection, we observed that RSV disease severity was associated with greater deviation in microbial community profiles when compared to healthy children,” the researchers say. “Importantly, also during the recovery phase, the respiratory microbiome was linked with the presence of residual respiratory symptoms.”

Studies have suggested that the early-life microbiota of the nose and throat influences the severity of RSV infections, but exactly how certain bacteria affect disease severity and long-term symptoms is unclear.

To investigate the microbiota’s role in RSV infection severity, researchers led by Maartje Kristensen at the University Medical Center Utrecht, the Netherlands, set out to analyze 1,537 swabs taken from the back of the nose and upper throat of more than 1,135 infants across five countries.

Disease severity

The researchers found that the composition of the respiratory microbiota of infants during and after RSV infection differed from that of healthy infants, with lower microbial diversity and richness after infection. The analysis also revealed shifts in the overall composition between the acute and recovery phases of infection.

Specific groups of microbes, such as those dominated by Moraxella, Haemophilus or Streptococcus bacteria, were linked to RSV infection, with the microbiota composition varying with increasing disease severity. 

In severe cases, bacteria such as Streptococcus pneumoniae were more prevalent, while the levels of Corynebacterium and other beneficial microbes were reduced. After severe RSV infection, some long-term respiratory symptoms were linked to a higher abundance of Haemophilus and lower levels of Dolosigranulum bacteria, the researchers found. 

Exacerbating inflammation

Further analyses revealed that the early-life microbiota composition did not predict whether infants would get RSV infections in their first year of life. “The early-life respiratory microbial community composition seems unrelated to the risk of RSV infection, which may be more driven by risk factors like age at RSV season, and crowding,” the researchers say.

The findings suggest that alterations in the early-life microbiota can contribute to inflammation, which may exacerbate the severity of RSV infections, although more research is needed to understand the long-term effects of these microbial changes, such as their role in asthma development. 

The study also highlight the importance of studying the microbiota over time. Long-term sampling of respiratory microbes could help scientists better understand how early microbial patterns influence susceptibility to RSV and disease severity, the authors say.

What this research adds
Researchers examined the upper airways microbiota of 3,160 healthy Dutch people aged zero to 80 years old. A person’s nasal microbiota is more similar to their own throat microbiota than to the throat microbiota of others. While the nasal microbiota continues to evolve into early adulthood, the throat microbiota reaches full development during childhood. The nasal microbiota is influenced by age, sex and respiratory infections, whereas the throat microbiota is shaped by lifestyle factors such as smoking and antibiotic use.

Conclusions
The findings suggest that the development and maturation of the nasal microbiota are influenced by age and sex, while lifestyle factors shape the throat microbiota.

The microbiota of the upper airways can influence a person’s susceptibility to acute infections and long-term conditions such as asthma. Now, researchers have mapped the upper airway microbiota of healthy individuals, shedding light on its role in respiratory health and disease.

The findings, published in Cell, suggest that the development and maturation of the nasal microbiota are influenced by age and sex, while lifestyle factors shape the throat microbiota.

Because the upper respiratory tract acts as a barrier to pathogens and interacts with the immune system, the microbes residing in the nose and throat have been linked to many respiratory conditions. However, most studies have focused on the upper respiratory tract microbiota in infants; little is known about how this microbiota evolves throughout life and impacts overall health.

To characterize the changes of the upper respiratory tract microbiota across the lifespan, Mari-Lee Odendaal at Utrecht University in the Netherlands and her colleagues examined 5,500 samples from the nasal and oral cavities of 3,160 healthy Dutch people aged zero to 80 years old.

Microbiota maturation

The researchers found that the microbiota of the upper airways, particularly in the nose and throat, changes as people age. However, different areas have unique microbiota patterns. For example, the noses and throats of younger people have more bacteria overall but less variety among them. In contrast, older individuals have a more diverse range of bacteria in their noses and throats but a lower number of bacteria. 

The amounts of bacteria such as Dolosigranulum pigrum and Corynebacterium species also change with age, with D. pigrum being more abundant in younger people. The abundance of this microbe has been linked to the absence of disease and the inhibition of potential pathogens.

A person’s nasal microbiota is more similar to their own throat microbiota than to the throat microbiota of others, the researchers also found. While the nasal microbiota continues to evolve into early adulthood, the throat microbiota reaches full development during childhood.

Knowledge gap

The team found sex differences in the nasal microbiota, with bacteria such as Lawsonella clevelandensis, Finegoldia magna and Peptoniphilus species being more abundant in males than females. These differences emerge during puberty, likely due to hormonal changes, the authors say.

Further analyses showed that the airway microbiota is altered in people who have recently had mild respiratory infection symptoms. More severe symptoms cause greater changes in the nasal microbiota. In contrast with the nasal microbiota, the throat microbiota is shaped by lifestyle factors such as smoking and antibiotic use, the researchers found. 

“We shed light on age-related dynamics of the [upper respiratory tract] microbiota in a general population, filling a knowledge gap that has persisted despite numerous investigations of the human microbiome,” the authors say.

What this research adds
Working in mice, researchers found that segmented filamentous bacteria (SFB) — a type of bacteria found in the gut — protects mice against infection with influenza virus. This protection also applied to respiratory syncytial virus and SARS-CoV-2, and it required the presence of immune cells called alveolar macrophages in the lung. Further experiments showed that alveolar macrophages disabled influenza virus by activating a component of the immune system called the complement system.

Conclusions
The results reveal that the severity of respiratory infections depends at least in part on a complex interplay between the gut microbiota and the immune system. If applicable to humans, the findings could help assess whether people with respiratory infections might advance to severe disease.

Respiratory viruses such as influenza and SARS-CoV-2, the virus that causes COVID-19, can result in severe disease. However, the outcomes of these respiratory infections vary widely among individuals. New research shows that a type of bacteria found in the gut protects mice against infection with influenza and other respiratory viruses.

The results, published in Cell Host & Microbe, reveal that the severity of respiratory infections depends at least in part on a complex interplay between the gut microbiota and the immune system. If applicable to humans, the findings could help assess whether people with respiratory infections might advance to severe disease. 

“We find it remarkable that the presence of a single common commensal bacterial species, amidst the thousands of different microbial species that inhabit the mouse gut, had such strong impacts in respiratory virus infection models,” says study co-senior author Richard Plemper at Georgia State University in Atlanta. 

Scientists suspect that gut microbes may be in part responsible for the variability observed in the clinical outcomes of people with respiratory infections, as gut bacteria have been implicated in many inflammatory diseases and associated immune responses. What’s more, previous studies have shown that wild mice have activated immune systems, which make them relatively resistant to infection with influenza A virus. 

Plemper and his colleagues set out to assess whether — and how — differences in specific microbial species can impact outcomes of respiratory viral infections in mice.

Microbiota differences

The researchers compared proneness to influenza infection in mice with defined differences in their gut microbiota composition. Disease symptoms and viral load in the animals’ lungs were measured several days after infection with influenza A virus.

Mice free of specific pathogens showed reduced viral loads in the lungs compared with “excluded flora” mice, which lack a panel of disease-modulating commensal microbes. These results suggest that one or more of the microbes absent in “excluded flora” mice might confer protection against influenza.

Of the microbes known to be excluded in these mice, segmented filamentous bacteria (SFB) — a type of bacteria found in the gut — stood out as a potential modulator of susceptibility to influenza infection. “SFB is a major contributor to, albeit not the sole mediator of, spontaneous resistance of mice to rotavirus, an intestinal pathogen, that arose in some mouse colonies,” the researchers say.

Immune activation

The protection against infection also applied to respiratory syncytial virus and SARS-CoV-2, and it required the presence of immune cells called alveolar macrophages in the lung, the researchers found. 

In mice lacking SFB, alveolar macrophages were quickly depleted as respiratory virus infection progressed. In contrast, the alveolar macrophages of mice with SFB were able to prevent flu-triggered depletion and inflammatory signaling. Further experiments showed that alveolar macrophages disabled influenza virus by activating a component of the immune system called the complement system. 

“We find it highly unlikely that segmented filamentous bacteria are the only gut microbes capable of impacting the phenotype of alveolar macrophages, and consequently, proneness to respiratory virus infection,” says study co-senior author Andrew Gewirtz. “Rather, we hypothesize that gut microbiota composition broadly influences proneness to respiratory virus infection. Microbiota mediated programming of basally resident alveolar macrophages may not only influence the severity of acute respiratory virus infection, but may also be a long-term post-respiratory virus infection health determinant.”

During the 8th annual Microbiome Movement Drug Development Europe, held in Barcelona (Spain), Microbiomepost conducted an exclusive interview with Aran Singanayagam, research group leader at Imperial College London (UK). 

We delved into the critical functions of the respiratory microbiome in maintaining healthy bodily equilibrium and examined how disturbances in the airway microbiome are instrumental in the development of chronic lung diseases. Additionally, we explored the promising horizon of microbiome manipulation as an innovative approach to treat chronic pulmonary conditions.