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.”

What this research adds
Researchers developed three-dimensional cell models that mimic the structure and function of human bladder tissue. Then, they exposed the ‘mini bladders’ to six bacterial species commonly found in real human bladders: Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Proteus mirabilis, Streptococcus agalactiae and Klebsiella pneumoniae. The team found that bacteria use different strategies, including forming pod-like structures within the bladder wall, to survive antibiotic treatment and hide from the immune system.

Conclusions
The findings indicate that effective treatments for recurrent UTIs may require the ability to penetrate human tissues, suggesting that current approaches to diagnosing and treating the infections may be inadequate for people who frequently suffer from them.

Urinary tract infections, or UTIs, affect about 400 million people worldwide every year. Now, working in artificial bladders, researchers have found that disease-causing bacteria use different strategies, including forming pod-like structures within the bladder wall, to survive antibiotic treatment and hide from the immune system. 

The findings, published in Science Advances, suggest that current approaches to diagnosing and treating UTIs may be inadequate for people who frequently suffer from them.

“Some species of both ‘good’ and ‘bad’ bugs formed pods within the bladder wall, most likely as a way of surviving in this harsh environment,” says study senior author Jennifer Rohn at University College London. “If this happens with a friendly bug, this isn’t a problem. But if the bug is causing an infection, this poses a serious problem for diagnosis and treatment because the bacteria aren’t necessarily going to be detected in a urine sample or be in a position where oral antibiotics can reach them.”

UTIs, usually caused by bacteria from feces entering the urinary tract, are one of the most common bacterial infections in humans, with about 30% of people having a recurring UTI within six months. UTIs have been typically studied in animals and cultured cells, but it’s unclear how pathogenic bacteria interact with the human bladder during infection. To examine the behavior of pathogens in the human bladder, Rohn and her team developed three-dimensional cell models that mimic the structure and function of bladder tissue. 

Mini bladders

The researchers exposed the ‘mini bladders’ to six bacterial species commonly found in real human bladders: Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Proteus mirabilis, Streptococcus agalactiae and Klebsiella pneumoniae.

The team found that bacteria use different strategies to survive antibiotic treatment and hide from the immune system. For example, some bacteria — both commensals and pathogens — invaded cells, whereas others formed pod-like structures with other bacteria within the bladder wall.

“One of the key observations was the importance of persistence,” Rohn says. “If you want to be a successful pathogen, you have to have strategies that help you to survive treatment and hide from patrolling immune cells, which means you live to fight another day.”

Improving diagnostics

The researchers also found that pathogens triggered the production of immune molecules called cytokines and the shedding of the top layer of the bladder wall, whereas commensal bacteria colonized the bladder tissue without causing an immune response.

“Based on our results, next-generation diagnostics for UTIs could focus on identifying ‘bad’ bugs based on how the body responds, rather than trying to spot the presence of problem bacteria among the background noise of the microbiome,” says study first author Carlos Flores.
Finally, the team discovered that a specific cell-surface component of E. coli bacteria, called FimH, was required for the formation of bacterial communities within cells, but not for cell invasion. Because FimH is a popular target for the development of antibiotic alternatives to treat UTIs, this finding highlights the need to develop alternative drugs that target other bacterial components besides FimH, the authors say.

What this research adds
Researchers analyzed blood samples and joint fluids from people with rheumatoid arthritis with and without periodontal disease. People with periodontal disease experienced repeated flare-ups of rheumatoid arthritis and had higher levels of oral bacteria in blood, where the microbes were targeted by specific immune cells. These cells released anti-citrullinated protein antibodies (ACPAs), a type of antibodies against an individual’s own proteins that are commonly observed in people with rheumatoid arthritis.

Conclusions
The findings suggest that periodontal disease may contribute to rheumatoid arthritis by triggering specific immune responses.

Periodontal disease — the infection and inflammation of the gums and bone that surround the teeth — affects about 47% of adults in the United States and is common in people with rheumatoid arthritis, an autoimmune disease that mainly attacks the joints. New research suggests that in people with rheumatoid arthritis and periodontal disease, oral bacteria can break into the bloodstream and trigger inflammation from immune cells. 

The findings, published in Science Translational Medicine, indicate that periodontal disease may contribute to rheumatoid arthritis by triggering specific immune responses. “Future studies are needed to determine whether improved oral care may provide therapeutic benefit in the management of [rheumatoid arthritis],” the researchers say. 

People with rheumatoid arthritis have an unusually high risk of periodontal disease, which can damage the oral mucosa, allowing mouth bacteria to enter the bloodstream. Scientists have suspected that periodontal disease could trigger inflammation elsewhere in the body, but the mechanisms behind this process have remained mysterious. 

To investigate the link between the two conditions, a team of researchers led by William Robinson at Stanford University and Dana Orange at Rockefeller University analyzed blood samples and joint fluids from people with rheumatoid arthritis with and without periodontal disease.

Flare-up trigger

The researchers collected blood samples from five women with rheumatoid arthritis, some of whom had periodontal disease, each week over the course of one to four years. The team also examined joint fluids and plasma samples from two other groups of people with rheumatoid arthritis.

Compared to people without periodontal disease, those with the condition had higher levels of oral bacteria in their blood. The most common bacteria were Streptococcus species, which were also the most abundant microbes detected in mouth swabs.

People with periodontal disease also experienced repeated flare-ups of rheumatoid arthritis, the researchers found. The presence of oral bacteria in blood appeared to trigger the activation of immune responses in people with periodontal disease and rheumatoid arthritis flare-ups.

Contributing to inflammation

Further experiments suggested that oral bacteria in the blood activated specific immune cells, which released a type of antibodies that are commonly observed in people with rheumatoid arthritis. These antibodies, known as anti-citrullinated protein antibodies (ACPAs), are directed against an individual’s own proteins that have undergone citrullination — a reaction that converts the amino acid arginine into the amino acid citrulline.

The researchers discovered that bacteria enriched in the mouth of people with periodontal disease are highly citrullinated. The team also found that ACPAs bind citrullinated bacterial peptides from people with periodontal disease.

These and other experiments, the researchers say, “indicate that patients develop antibodies that bind citrullinated oral commensal bacterial proteins that are cross-reactive against known human citrullinated autoantigens.” 

The findings also suggest, they add, “that [periodontal disease], through repeated mucosal breaks, results in recurring innate and adaptive immune activation that may contribute to the pathogenesis of [rheumatoid arthritis].”

What this research adds
By analyzing urine samples from 75 postmenopausal women, researchers found that those with a history of recurrent UTIs had in their urogenital microbiotas high levels of bacteria that are typically found during an active infection. Women who didn’t suffer from recurrent UTIs had high levels of the hormone estrogen, and their urogenital microbiotas were enriched in Bifidobacterium and Lactobacillus bacteria. The researchers also identified antimicrobial resistance genes that were frequently found in the urogenital microbiotas of women with recurrent UTIs.

Conclusions
The findings suggest that recurrent UTIs and estrogen can shape the urogenital microbiota in ways that may protect against recurrent infections. The results may also help inform better treatments for recurrent UTIs.

More than half of women suffer a urinary tract infection (UTI) in their lifetimes, and about half of those who have gone through menopause and who contract a UTI will have a recurrent infection. New research indicates that recurrent UTIs and estrogen can shape the urogenital microbiota in ways that may protect against recurrent infections.

The findings, published in Cell Reports Medicine, may also help inform better treatments for recurrent UTIs.

Recurrent UTIs are often treated with antibiotics, but the number of UTIs caused by bacteria resistant to most first-line antibiotics is increasing. Alternative therapeutic approaches are needed to improve the clinical outcome and the quality of life of women with recurrent UTIs, the researchers say.

In the past decade, several studies have shown that the urogenital microbiota may play a role in recurrent UTIs, which are defined as more than two UTIs in a six-month period. However, how changes in the microbiota influence susceptibility to recurrent infections is unknown.

To identify such changes, Nicole De Nisco at the University of Texas at Dallas and her colleagues set out to analyze urine samples from 75 postmenopausal women.

Microbial differences

To validate the presence of living microbes within the urogenital microbiotas of participants, the researchers combined urine culture with DNA sequencing. They detected a total of 276 bacterial, archaeal and fungal species across 106 genera. Bacteria represented more than 99% of the urogenital microbiota, with Firmicutes, Actinobacteria, Proteobacteria and Bacteroidetes dominating the community.

Women with a history of recurrent UTIs had in their urogenital microbiotas high levels of bacteria that are typically found during an active infection, including uropathogenic Escherichia coli, the major pathogen in most types of UTIs, as well as Klebsiella pneumoniae, Enterococcus faecalis and Streptococcus agalactiae. Instead, in the urogenital microbiotas of women without active UTI, the researchers found mostly Lactobacillus, Bifidobacterium, Gardnerella, Streptococcus, Staphylococcus and Actinobaculum. 

The team observed that about one in four women without active UTIs had high abundances of Bifidobacterium and Lactobacillus in their urogenital microbiotas. Lactobacillus are probiotic bacteria that may protect against infection.

Estrogen effect

The researchers found that the hormone estrogen was associated with the presence of Lactobacillus bacteria in the urogenital microbiota. Estrogen is thought to promote Lactobacillus colonization of the vaginal and urinary tract.

On the other hand, in the urogenital microbiotas of women with recurrent UTIs, the researchers identified genes that confer resistance to front-line antibiotics, such as trimethoprim-sulfamethoxazole, fluoroquinolones and nitrofurantoin. 

The study, the researchers say, “provides a robust foundation for further mechanistic studies of the role of the urogenital microbiome in [recurrent] UTI susceptibility and disease progression that are necessary for the development of urogenital microbiome-aware alternative therapies for a [recurrent] UTI.”

What this research adds
Researchers analyzed urine, blood and stool samples from 31 women — 15 with a history of recurring UTIs and 16 without. Over the course of a year, 24 UTIs occurred, all in the group of women with a history of repeated UTIs. In their guts, both groups had UTIs-causing E. coli bacteria, which occasionally spread to their bladders. However, women with recurring infections had a less diverse gut microbiota: in particular, they had increased levels of Bacteroidetes and lower abundance of Firmicutes compared to women without recurring infections. Those with recurrent UTIs also had low levels of bacteria capable of producing butyrate, a short-chain fatty acid with anti-inflammatory effects, as well as higher levels of an immune molecule linked to gut inflammation.

Conclusions
The findings suggest that recurrent UTIs are in part caused by alterations of the gut microbiota and different immune response to bacterial bladder colonization, and may have important implications for the treatment of UTIs.

Infections of the urinary tract are common among women, with a quarter of sufferers experiencing recurring infections. A new study suggests that people with recurrent infections have different immune responses and imbalances in their gut microbiota makeup.

The findings, published in Nature Microbiology, may have important implications for the treatment of urinary tract infections, or UTIs. “Our study clearly demonstrates that antibiotics do not prevent future infections or clear UTI-causing strains from the gut, and they may even make recurrence more likely by keeping the microbiome in a disrupted state,” says lead study author Colin Worby at the Broad Institute.

Antibiotics are typically used to ease symptoms of UTIs, which are caused by bacteria in the urinary tract and characterized by frequent and painful urination. Scientists have known that higher levels of E. coli bacteria in the gut may be contributing to UTIs, but the exact causes of recurring infections remain unclear.

To understand why some people experience recurring infections whereas others don’t, Worby and his colleagues set out to analyze urine, blood and stool samples from 31 women — 15 with a history of recurrent UTIs and 16 without.

Repeated infections

Over the course of a year, 24 UTIs occurred, all in the group of women with a history of repeated UTIs. Once a woman developed a UTI, the team collected and analyzed additional urine, blood and stool samples.

In their guts, both groups of women had UTIs-causing E. coli bacteria, which occasionally spread to their bladders. However, women with recurring infections had a less diverse gut microbiota: in particular, they had increased levels of Bacteroidetes and lower abundance of Firmicutes compared to women without recurring infections.

Those with recurrent UTIs also had low levels of bacteria capable of producing butyrate, a short-chain fatty acid with anti-inflammatory effects, as well as higher levels of an immune molecule linked to gut inflammation. “We think that women in the control group were able to clear the bacteria from their bladders before they caused disease, and women with recurrent UTI were not, because of a distinct immune response to bacterial invasion of the bladder potentially mediated by the gut microbiome,” Worby says.

Antibiotics effect

The team also found that antibiotics that are commonly used for treating UTIs eliminated disease-causing bacteria from the bladder but not from the gut of women with recurring UTIs. Surviving bacteria in the gut can multiply and spread to the bladder again, causing another UTI, the researchers say.

“Our study clearly demonstrates that antibiotics do not prevent future infections or clear UTI-causing strains from the gut,” Worby says. “And they may even make recurrence more likely by keeping the microbiome in a disrupted state.”

The researchers hypothesized that restoring a healthy gut microbiota, for example through fecal transplants, may limit recurring infections. Fecal transplants have shown promise in treating repeated intestinal infections caused by Clostridioides difficile bacteria. Other promising approaches include the development of small molecules that target only UTI-causing E. coli, the researchers say.

What is already known on this topic
Infection with Clostridioides difficile (C. difficile), a bacterium that causes life-threatening inflammation of the gut, is an emerging threat caused by the use of broad-spectrum antibiotics. Previous studies have shown that the drug ebselen can stop C. difficile infection by targeting bacterial toxins rather than the bacterium itself.

What this research adds
Researchers found that ebselen, which is already being tested in human clinical trials, protects rodents from C. difficile-associated tissue damage without altering the composition of the gut microbiota. After antibiotic treatment, the drug promotes recovery of the microbiota, which in turn alleviates gut inflammation.

Conclusion
The findings support ebselen translation into the clinic for the treatment of C. difficile infection.

Infection with Clostridioides difficile (C. difficile), a bacterium that causes life-threatening inflammation of the gut, is an emerging threat caused by the use of broad-spectrum antibiotics. Now, researchers have found that ebselen, a drug already in human clinical trials, protects rodents from C. difficile-associated tissue damage and bolsters recovery of the microbiota after antibiotic treatment, further alleviating gut inflammation.

The findings, published in Cell Reports Medicine, support ebselen translation into the clinic for the treatment of C. difficile infection. “The anti-inflammatory properties of ebselen, combined with its anti-toxin function, help to mitigate the major clinical challenges of [C. difficile infection], including recurrence, microbial dysbiosis, and colitis,” say Matthew Bogyo at Stanford School of Medicine and his team, who conducted the research.

In 2015, in an attempt to combat C. difficile without using antibiotics, Bogyo and his colleagues looked for compounds that could stop C. difficile infection by targeting bacterial toxins rather than the bacterium itself. They focused on a drug called ebselen, which was already in clinical trials for conditions such as stroke.

This time around, the researchers set out to test the efficacy of ebselen in a hamster model of C. difficile infection.

Antibiotic alternative

The researchers first gave the rodents antibiotics to induce gut dysbiosis, then infected them with C. difficile.

Treatment with ebselen resulted in diminished inflammation and decreased tissue damage in the hamsters’ gut. The drug also reduced recurrence rates, with 4 of 10 hamsters surviving for at least 20 days.

Ebselen did not alter neither the diversity nor the composition of the rodents’ gut microbiota. On the contrary, the drug promoted recovery of the microbiota after antibiotic treatment in both healthy hamsters and those infected with C. difficile.

Towards the clinic

The team found that most rodents treated with ebselen and the antibiotic vancomycin recovered, while all of the rodents treated only with vancomycin continued to have an altered gut microbiota. Recovery of the microbiota appeared to further alleviate gut inflammation.

“Together with our previous work, we show that treatment with the orally administered compound ebselen reduces short-term colitis caused by [C. difficile infection],” the researchers say. The drug, they add, also reduces disease recurrence and gut dysbiosis associated with antibiotic treatment.

Together, the findings suggest that ebselen can be used to prevent severe inflammation of the gut in people at high risk of C. difficile infection, the researchers say.

What is already known on this topic
Around the world, overuse of antibiotics is driving the spread of bacterial “superbugs” that are resistant to antimicrobials, making people more vulnerable to diseases like tuberculosis and bacterial pneumonia. To counter the spread of antibiotic-resistant bacteria, it is important to understand how resistance spreads within microbial communities.

What this research adds
Researchers looked at the effect of three human gut microbiota communities on the growth and resistance evolution of a strain of Escherichia coli. Gut microbial communities suppressed E. coli growth and gut colonization, and prevented it from evolving antibiotic resistance. The E. coli strain only evolved antibiotic resistance in the absence of the gut microbiota.

Conclusion
The findings support the idea that interactions with resident microbiota can inhibit antibiotic-resistance evolution of bacterial species.

Around the world, overuse of antibiotics is driving the spread of bacterial “superbugs” that are resistant to antimicrobials, making people more vulnerable to diseases like tuberculosis and bacterial pneumonia. A new study shows that interactions with the resident gut microbiota could suppress the proliferation and antibiotic-resistance evolution of superbugs.

The findings, published in PLOS Biology, could help to predict resistance evolution from genetic data collected through surveillance efforts, the study authors say.

To counter the spread of antibiotic-resistant microbes, scientists have been looking at how resistance is acquired by bacteria and how it spreads within microbial communities. Interactions with other microbial communities might reduce the proliferation of superbugs through competition for resources or space. On the other hand, these relationships may also stimulate the growth and evolution of resistant bacteria through the exchange of genetic material.

To analyze the impact of interactions with other microorganisms on antibiotic-resistance evolution, Michael Baumgartner at ETH Zürich in Switzerland and his colleagues grew a strain of Escherichia coli in the presence or absence of an antibiotic and of three samples of gut microbiota, each from a different person.

Microbiota effects

In the presence of the antibiotic and the gut microbiota samples, the E. coli strain became less abundant or completely disappeared. In the absence of the antibiotic, microbiota communities still suppressed the E. coli strain on average, but the effect varied depending on the sample origin. The microbiota from human donor 3 suppressed the growth of the E. coli strain by about 54%, while the microbiota from donor 2 reduced the proliferation of E. coli by 24%. The microbiota from donor 1 completely eliminated the E. coli strain.

At the beginning of the experiment, all the microbiota communities were dominated by Lachnospiraceae and Ruminococcaceae. However, these bacteria became less abundant over time.

Antibiotic-resistance genes

The researchers did not observe resistant variants of the E. coli strain when they exposed it to the microbial communities from human microbiota samples. But resistant variants appeared towards the end of the experiment in the absence of the gut microbiota communities. “Thus, the resident microbial community from human microbiome samples suppressed antibiotic-resistance evolution in our [E. coli] strain,” the researchers say.

When the team analyzed the DNA of the antibiotic-resistant strains, they found mutations in genes related to membranes, stress responses, and transcription. Some of these genes are known to be involved in resistance to a specific class of antibiotics.

Bacterial interactions

Further experiments showed that specific conditions in the gut microbiota communities from human donors influenced the bacteria’s ability to transfer antibiotic-resistance genes. The findings, the researchers say, “can explain why our [E. coli] strain failed to acquire some of these beneficial resistance genes.”

The findings support the idea that interactions with resident microbiota can inhibit antibiotic-resistance evolution of bacterial species. However, more work in needed to uncover specific bacterial families within the gut microbiota that affect colonization and antibiotic-resistance evolution of invading species, the researchers say. Identifying resistance genes and acquiring information about factors that influence the genetic transfer of such genes will be important to combat the spread of superbugs, they say.

What is already known on this topic
Infections by Clostridioides difficile (C. difficile), which can cause life-threatening inflammation of the gut, have been traditionally associated with hospitalization and antibiotic use. But recent studies show increasing rates of C. difficile infection among people not considered to be at high risk.

What this research adds
Researchers analyzed surveys of the gut microbiota of individuals who had diarrhea and were not treated with antibiotics, and then the team tested the association between diarrhea and C. difficile infection in mice. The results show that diarrheal events, such as those triggered by food poisoning and laxative abuse, can increase susceptibility to C. difficile infection.

Conclusion
The study suggests that diarrheal events create a window of susceptibility to C. difficile infection, and the development of new therapies that aim to increase colonization resistance during this window could help to reduce the prevalence of C. difficile.

Infections by Clostridioides difficile (C. difficile), which can cause life-threatening inflammation of the gut, have been traditionally associated with hospitalization and antibiotic use. But recent studies show increasing rates of C. difficile infection among people not considered to be at high risk. Now, a study in mice has shown that events that trigger diarrhea, such as food poisoning and laxative abuse, can increase susceptibility to C. difficile infection.

The findings, published in Nature Microbiology, show that the risk of colonization with C. difficile is highest during recovery from acute diarrhea. “Roughly 48 million people contract a foodborne illness every year in the United States, highlighting the days immediately following illnesses like these as a substantial target for reducing the prevalence of C. difficile,” the researchers say.

To determine whether diarrhea triggers colonization by C. difficile, David VanInsberghe at the Massachusetts Institute of Technology in Cambridge and his colleagues analyzed previous studies that surveyed the gut microbiota of people who had diarrhea, caused by either food poisoning or Vibrio cholerae infection. None of the individuals was treated with antibiotics.

Diarrheal trigger

The researchers observed that C. difficile infection occurred as people recovered from diarrheal illnesses, and individuals remained colonized with C. difficile for up to a year. The number of C. difficile bacteria shed in a carrier’s stool was variable and could increase by more than 1,000 times in one day, likely influencing the transmissibility of C. difficile outside of hospitals.

These results underscore that C. difficile infection is not a common hospital transmission, VanInsberghe says. “In our study, two of the people we followed with high temporal resolution became carriers outside of the hospital.”

Next, the team set out to study surveys of the microbiota of people who did not have recent diarrhea. The researchers found that C. difficile was rare in these individuals, further suggesting that diarrhea facilitates C. difficile colonization.

Dangerous association

To test the association between diarrhea and C. difficile infection, the team fed mice increasing quantities of laxatives while exposing them to C. difficile spores, and then monitored the animals’ feces for C. difficile blooms.

Mice treated with high quantities of laxatives had more C. difficile blooms in their feces than those treated with lower quantities of laxatives. Mice that weren’t given laxatives had no detectable C. difficile in their stool.

The findings suggest that diarrheal events create a window of susceptibility to C. difficile infection, and the development of new therapies that aim to increase colonization resistance during this window could help to reduce the prevalence of C. difficile, the researchers say.

“I believe that there is a lot of rethinking of C. diff infections at the moment and I hope our study will help contribute to ultimately better manage the risks associated with it,” says study senior author Martin Polz.

What is already known on this topic
The composition of the nasal microbiota influences many respiratory conditions. But little is known about the mechanisms that lead to the development of a healthy microbiota in the nose.

What this research adds
Researchers analyzed the nasal microbiota from more than 450 people of different ages and observed a decline of pathogenic bacteria before adulthood, together with an increase of the commensal Staphylococcus epidermidis. In a lab dish, S. epidermidis stimulated nasal cells to produce antimicrobial molecules, which could also kill pathogenic bacteria in mice.

Conclusion
The findings reveal that S. epidermidis plays a key role in the maturation of a healthy nasal microbiota, likely by stimulating the production of antimicrobial molecules in the nose.

The commensal microbe Staphylococcus epidermidis contributes to a healthy nasal microbiota, likely by stimulating the production of antimicrobial molecules in the nose. That’s the conclusion of a new study, published in Cell Host and Microbe, which analyzed how the nasal microbiota changes from childhood to adulthood.

Scientists have known that the composition of the nasal microbiota influences many respiratory conditions. But the mechanisms that lead to the development of a healthy nasal microbiota are unclear.

To address this question, a team of researchers led by Qian Liu at Shanghai Jiaotong University analyzed the nasal microbiota of 155 children, 171 young adults, and 141 seniors.

Age shift

The human nasal microbiota changed markedly with age: microbial diversity and the dominance of Moraxella bacteria decreased in adulthood, while the presence of Staphylococcus increased by more than 4 times.

The researchers observed a substantial decline of pathogenic bacteria such as Dolosigranulum pigrum before adulthood. This decrease was accompanied by an increase of the commensal microbe Staphylococcus epidermidis. In seniors, the increase in Staphylococcus and decrease in Dolosigranulum observed in young adults were in part reversed.

Helpful microbe

To test whether the decrease in pathogenic microbes in adult noses was a result of the increase in Staphylococcus bacteria, the team grew nasal microbiota samples in a lab dish. S. epidermidis was more abundant in samples from young adults and, to a lesser extent, seniors than in samples from children. What’s more, samples with the highest abundance of S. epidermidis had fewer pathogens than samples with lower levels of the bacterium.

When grown in a lab dish together with nose cells, S. epidermidis stimulated the cells to produce antimicrobial molecules that killed pathogenic bacteria. In mice, S. epidermidis strains were able to outcompete pathogens such as Staphylococcus aureus and Moraxella catarrhalis, leading to decreased signs of infection caused by these bacteria.

The findings reveal that S. epidermidis plays a key role in limiting the growth of pathogenic bacteria in the nose and preventing respiratory infections, the researchers say.

What is already known on this topic
Maternal antibodies—passed onto the offspring both through the placenta during pregnancy and via breastfeeding shortly after birth—are known to protect newborn babies from various infections such as Streptococcus and influenza viruses. But it remains unclear how these antibodies offer immune protection against pathogens that the mother or the newborn haven’t encountered in the past.

What this research adds
By studying newborn mice lacking immune cells and their mothers, researchers found that part of the protective effect of mother’s milk against the disease-causing Escherichia coli microbe comes from the bacteria that reside in the mother’s gut.

Conclusion
The findings could inform the development of vaccines derived from microbial molecules and the use of commensal microbes as probiotics that protect against infections that cause diarrhea.

Mother’s milk is known to protect newborns from certain infections. Now a study in mice shows that part of maternal milk’s protective effects comes from the bacteria that reside in the mother’s gut.

The findings, published in Nature, could inspire new microbiota-derived therapies and vaccines against dangerous infections. “Another therapeutic avenue could be the use of commensal microbes as probiotics that protect against diarrheal disease,” says study senior author Dennis Kasper, an immunologist at Harvard Medical School in Boston, Massachusetts. According to the World Health Organization, infectious diarrhea caused by E. coli or rotavirus kills more than 500,000 people every year worldwide.

For years, scientists have known that maternal antibodies—passed onto the offspring both through the placenta during pregnancy and via breastfeeding shortly after birth—protect newborn babies from various infections such as Streptococcus and influenza viruses. But it remains unclear how these antibodies offer immune protection to pathogens that the mother or the newborn haven’t encountered in the past, the researchers say.

So Kasper and his team set out to analyze the development of neonatal antibodies by studying newborn mice that were genetically engineered to lack antibody-producing immune cells. Some of the newborn mice were raised by mothers that also lacked antibody-producing immune cells and as a result couldn’t produce and pass on protective antibodies. Another group of newborn mice was raised by mothers that had normal immune systems.

Mum’s bugs

The researchers infected both groups of newborn mice with a strain of Escherichia coli (E. coli) that causes a dangerous, potentially deadly form of infectious diarrhea.

Newborn mice exposed to protective antibodies from their mothers had 33 times fewer E. coli bacteria in their gut than newborn mice that were not exposed to such antibodies. Newborn rodents lacking protective antibodies developed widespread diarrheal disease.

The team also showed that Pantoea, a microbe that resides in the gut of mice and other mammals, including people, was responsible for triggering the development of protective antibodies.

Maternal protection

Next, the researchers analyzed a molecule called Fc receptor, which helps to transfer protective antibodies from the mother to the fetus through the placenta. The results reveal that this receptor also transfers milk-derived antibodies from the gut of newborns to their bloodstream, ensuring wider protection against infection. Adult mice, whose Fc receptor is no longer functional, did not transfer protective antibodies from their gut to the bloodstream.

While it’s unclear whether their findings apply to people, the study could point to new ways of protecting newborn babies from life-threatening infections, the researchers say. The results also support the idea that the microbial communities of the body play an important role in health and disease.

“Our results help explain why newborns are protected from certain disease-causing microbes despite their underdeveloped immune systems and lack of prior encounters with these microbes,” Kasper says.