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Babies born vaginally have a different microbiome to those born by Caesarean section and have heightened responses to childhood vaccinations, according to a new study heralded as “interesting and important” by experts.
The microbiome is known to play a role in immune responses to vaccination. However, the relationship between early-life effects on intestinal microbiota composition and subsequent childhood vaccine responses had remained poorly understood. In the new study, “the findings suggest that vaginal birthing resulted in a microbiota composition associated with an increase in a specific type of antibody response to two routine childhood vaccines in healthy babies, compared with Caesarean section,” the authors said.
Researchers from the University of Edinburgh, with colleagues at Spaarne Hospital and University Medical Centre in Utrecht, and the National Institute for Public Health and the Environment in The Netherlands, tracked the development of the gut microbiome in a cohort of 120 healthy, full-term infants and assessed their antibody levels following two common childhood vaccinations.
The study, published in Nature Communications, found “a clear relationship between microbes in the gut of those babies and levels of antibodies.” Not only was vaginal birth associated with increased levels of Bifidobacterium and Escherichia coli in the gut microbiome in the first months of life but also with higher IgG antibody responses against both pneumococcal and meningococcal vaccines.
Antibody responses doubled after vaginal birth
The babies were given pneumococcal and meningococcal vaccinations at 8 and 12 weeks, and saliva was collected at follow-up visits at ages 12 and 18 months for antibody measurement. In the 101 babies tested for pneumococcal antibodies, the researchers found that antibody levels were twice as high among babies delivered naturally, compared with those delivered by C-section. High levels of two gut bacteria in particular – Bifidobacterium and E. coli – were associated with high antibody responses to the pneumococcal vaccine, showing that the microbiome mediated the link between mode of delivery and pneumococcal vaccine responses.
In 66 babies tested for anti-meningococcal antibodies, antibodies were 1.7 times higher for vaginally-born babies than those delivered via C-section, and high antibody levels were particularly associated with high levels of E. coli in the babies’ microbiome.
The results were also influenced by breast-feeding, which even among children born vaginally was linked with 3.5 times higher pneumococcal antibody levels, compared with those of formula-fed children. In contrast, levels of antibodies against meningococcus were unaffected by breast-feeding status.
Microbiome ‘sets level of infection protection’
The team said: “The baby acquires Bifidobacterium and E. coli bacteria through natural birth, and human milk is needed to provide the sugars for these bacteria to thrive on.” They explained: “The gut microbiome is seeded at birth, developing rapidly over the first few months of life, and is influenced mostly by delivery mode, breast-feeding, and antibiotic use.” The babies’ microbiome in early life contributes the immune system’s response to vaccines, they said, “and sets the level of protection against certain infections in childhood.”
Study lead Professor Debby Bogaert, chair of pediatric medicine at the University of Edinburgh, said: “I think it is especially interesting that we identified several beneficial microbes to be the link between mode of delivery and vaccine responses. In the future, we may be able to supplement those bacteria to children born by C-section shortly after birth through – for example, mother-to-baby ‘fecal transplants’ or the use of specifically designed probiotics.”
First author Dr. Emma de Koff, a microbiology trainee at the Amsterdam University Medical Center, said: “We expected to find a link between the gut microbiome and the babies’ vaccine responses, however we never thought to find the strongest effects in the first weeks of life.”
The findings “could help to inform conversations about C-sections between expectant mothers and their doctors,” commented the researchers, who said that they could also “shape the design of more tailored vaccination programs.” For example, in the future, vaccination schedules could be adjusted based on the method of delivery or analysis of the baby’s microbiome.
Potential to rectify immune system after Caesarean
Responding to the study, Professor Neil Mabbott, personal chair in immunopathology at the Roslin Institute of the University of Edinburgh, told the Science Media Centre: “This is a very interesting and important study. The authors show that infants delivered by a vaginal birth had higher responses to the two different types of vaccines against bacterial diseases, and this was associated with higher abundances of the potentially beneficial bacteria known as Bifidobacterium and E. coli in their intestines.”
He added: “This study raises the possibility that it may be possible to treat infants, especially Caesarean-delivered infants, with a bacterial supplement, or even a product produced by these beneficial bacteria, to help improve their immune systems, enhance their responses to certain vaccines and reduce their susceptibility to infections.”
The study raises important questions, he said, including whether the increased antibody levels from pneumococcal and meningococcal vaccinations following vaginal birth also leads to increased protection of the infants against infection or serious disease.
Sheena Cruickshank, immunologist and professor in biomedical sciences at the University of Manchester, England, commented: “It is now well established that the microbiome is important in immune development. In turn the mode of delivery and initial method of feeding is important in how the microbiome is first seeded in the baby.”
“However, other factors such as exposure to antibiotics and subsequent diet also play a role in how it then develops, making understanding the way the microbiome develops and changes quite complex. Microbes works as communities, and it can be difficult to determine whether changes in single species are important functionally. Breast milk also plays an important role in protecting the baby via transfer of maternal immunoglobulins, which will wane over a period of 6-12 months in the baby – thus ascertaining whether it’s the baby’s Ig is challenging.
“Given the complexity of the multitude of interactions, it is important that this is accounted for, and group sizes are large enough to ensure data is robust. Whilst this is an interesting study that adds to our knowledge of how the microbiome develops and the possible implications for immune development, it is still very preliminary, and the small group sizes warrant a need for further studies to verify this in larger groups.”
She added: “We will need to understand whether possible impacts of maternal delivery and feeding on immune development or vaccine responses can be restored by, for example, manipulating the microbiome.”
Professor Kim Barrett, vice dean for research at the University of California, Davis School of Medicine, said that, while further research was needed to uncover if and how manipulation of the human microbiome following C-section births might improve vaccine efficacy, “the work should at least lead to prompt additional consideration about an unintended consequence of the ever-increasing use of C-sections that may not be medically-necessary.”
Dr. Marie Lewis, researcher in gut microbiota at the University of Reading, England, said: “We have known for quite some time that the mode of delivery is incredibly important when it comes to the type of bacteria which colonize our guts. We also know that our gut bacteria in early life drive the development of our immune system, and natural births are linked with reduced risks of developing inflammatory conditions, such as asthma. It is therefore perhaps not really surprising that mode of delivery is also linked to responses to vaccinations.”
“The really interesting part here is the extent to which our gut microbiotas are accessible and changeable, and this important work could pave the way for administration of probiotics and prebiotics to improve vaccine responses in Caesarean-born children.”
‘Tantalizing data’
Dr. Chrissie Jones, associate professor of pediatric infectious diseases at the University of Southampton, and Southampton UK and education lead for the British Paediatric Allergy, Immunity, and Infection Group, said: “The link between method of delivery of the infant and the bacteria that live in the gut of the young infant has previously been shown. What is really interesting about this study is that, for the first time, the link between method of delivery (vaginal delivery vs. C-section), differences in bacterial communities of the gut, and differences in responses to vaccines is shown.”
“This study may give us fresh insights into the differences that we see in the amount of protective antibodies made after infant vaccination. It also gives us clues as to ways that we might be able to level the playing field for infants in the future – for instance, giving babies a safe cocktail of ‘friendly bacteria’ as a probiotic, or an additional dose of vaccine.”
“This study is the first step – it shows us a link or association but does not prove cause and effect that differences in the way babies are born alters how the immune system responds to vaccines. To prove this link we will need larger studies, but it is tantalizing data.”
The research was funded by Scotland’s Chief Scientist Office and the Netherlands Organisation for Scientific Research. DB received funding from OM pharma and Sanofi. All of the authors declared no other conflicts of interest.
A version of this article first appeared on Medscape.com.
Babies born vaginally have a different microbiome to those born by Caesarean section and have heightened responses to childhood vaccinations, according to a new study heralded as “interesting and important” by experts.
The microbiome is known to play a role in immune responses to vaccination. However, the relationship between early-life effects on intestinal microbiota composition and subsequent childhood vaccine responses had remained poorly understood. In the new study, “the findings suggest that vaginal birthing resulted in a microbiota composition associated with an increase in a specific type of antibody response to two routine childhood vaccines in healthy babies, compared with Caesarean section,” the authors said.
Researchers from the University of Edinburgh, with colleagues at Spaarne Hospital and University Medical Centre in Utrecht, and the National Institute for Public Health and the Environment in The Netherlands, tracked the development of the gut microbiome in a cohort of 120 healthy, full-term infants and assessed their antibody levels following two common childhood vaccinations.
The study, published in Nature Communications, found “a clear relationship between microbes in the gut of those babies and levels of antibodies.” Not only was vaginal birth associated with increased levels of Bifidobacterium and Escherichia coli in the gut microbiome in the first months of life but also with higher IgG antibody responses against both pneumococcal and meningococcal vaccines.
Antibody responses doubled after vaginal birth
The babies were given pneumococcal and meningococcal vaccinations at 8 and 12 weeks, and saliva was collected at follow-up visits at ages 12 and 18 months for antibody measurement. In the 101 babies tested for pneumococcal antibodies, the researchers found that antibody levels were twice as high among babies delivered naturally, compared with those delivered by C-section. High levels of two gut bacteria in particular – Bifidobacterium and E. coli – were associated with high antibody responses to the pneumococcal vaccine, showing that the microbiome mediated the link between mode of delivery and pneumococcal vaccine responses.
In 66 babies tested for anti-meningococcal antibodies, antibodies were 1.7 times higher for vaginally-born babies than those delivered via C-section, and high antibody levels were particularly associated with high levels of E. coli in the babies’ microbiome.
The results were also influenced by breast-feeding, which even among children born vaginally was linked with 3.5 times higher pneumococcal antibody levels, compared with those of formula-fed children. In contrast, levels of antibodies against meningococcus were unaffected by breast-feeding status.
Microbiome ‘sets level of infection protection’
The team said: “The baby acquires Bifidobacterium and E. coli bacteria through natural birth, and human milk is needed to provide the sugars for these bacteria to thrive on.” They explained: “The gut microbiome is seeded at birth, developing rapidly over the first few months of life, and is influenced mostly by delivery mode, breast-feeding, and antibiotic use.” The babies’ microbiome in early life contributes the immune system’s response to vaccines, they said, “and sets the level of protection against certain infections in childhood.”
Study lead Professor Debby Bogaert, chair of pediatric medicine at the University of Edinburgh, said: “I think it is especially interesting that we identified several beneficial microbes to be the link between mode of delivery and vaccine responses. In the future, we may be able to supplement those bacteria to children born by C-section shortly after birth through – for example, mother-to-baby ‘fecal transplants’ or the use of specifically designed probiotics.”
First author Dr. Emma de Koff, a microbiology trainee at the Amsterdam University Medical Center, said: “We expected to find a link between the gut microbiome and the babies’ vaccine responses, however we never thought to find the strongest effects in the first weeks of life.”
The findings “could help to inform conversations about C-sections between expectant mothers and their doctors,” commented the researchers, who said that they could also “shape the design of more tailored vaccination programs.” For example, in the future, vaccination schedules could be adjusted based on the method of delivery or analysis of the baby’s microbiome.
Potential to rectify immune system after Caesarean
Responding to the study, Professor Neil Mabbott, personal chair in immunopathology at the Roslin Institute of the University of Edinburgh, told the Science Media Centre: “This is a very interesting and important study. The authors show that infants delivered by a vaginal birth had higher responses to the two different types of vaccines against bacterial diseases, and this was associated with higher abundances of the potentially beneficial bacteria known as Bifidobacterium and E. coli in their intestines.”
He added: “This study raises the possibility that it may be possible to treat infants, especially Caesarean-delivered infants, with a bacterial supplement, or even a product produced by these beneficial bacteria, to help improve their immune systems, enhance their responses to certain vaccines and reduce their susceptibility to infections.”
The study raises important questions, he said, including whether the increased antibody levels from pneumococcal and meningococcal vaccinations following vaginal birth also leads to increased protection of the infants against infection or serious disease.
Sheena Cruickshank, immunologist and professor in biomedical sciences at the University of Manchester, England, commented: “It is now well established that the microbiome is important in immune development. In turn the mode of delivery and initial method of feeding is important in how the microbiome is first seeded in the baby.”
“However, other factors such as exposure to antibiotics and subsequent diet also play a role in how it then develops, making understanding the way the microbiome develops and changes quite complex. Microbes works as communities, and it can be difficult to determine whether changes in single species are important functionally. Breast milk also plays an important role in protecting the baby via transfer of maternal immunoglobulins, which will wane over a period of 6-12 months in the baby – thus ascertaining whether it’s the baby’s Ig is challenging.
“Given the complexity of the multitude of interactions, it is important that this is accounted for, and group sizes are large enough to ensure data is robust. Whilst this is an interesting study that adds to our knowledge of how the microbiome develops and the possible implications for immune development, it is still very preliminary, and the small group sizes warrant a need for further studies to verify this in larger groups.”
She added: “We will need to understand whether possible impacts of maternal delivery and feeding on immune development or vaccine responses can be restored by, for example, manipulating the microbiome.”
Professor Kim Barrett, vice dean for research at the University of California, Davis School of Medicine, said that, while further research was needed to uncover if and how manipulation of the human microbiome following C-section births might improve vaccine efficacy, “the work should at least lead to prompt additional consideration about an unintended consequence of the ever-increasing use of C-sections that may not be medically-necessary.”
Dr. Marie Lewis, researcher in gut microbiota at the University of Reading, England, said: “We have known for quite some time that the mode of delivery is incredibly important when it comes to the type of bacteria which colonize our guts. We also know that our gut bacteria in early life drive the development of our immune system, and natural births are linked with reduced risks of developing inflammatory conditions, such as asthma. It is therefore perhaps not really surprising that mode of delivery is also linked to responses to vaccinations.”
“The really interesting part here is the extent to which our gut microbiotas are accessible and changeable, and this important work could pave the way for administration of probiotics and prebiotics to improve vaccine responses in Caesarean-born children.”
‘Tantalizing data’
Dr. Chrissie Jones, associate professor of pediatric infectious diseases at the University of Southampton, and Southampton UK and education lead for the British Paediatric Allergy, Immunity, and Infection Group, said: “The link between method of delivery of the infant and the bacteria that live in the gut of the young infant has previously been shown. What is really interesting about this study is that, for the first time, the link between method of delivery (vaginal delivery vs. C-section), differences in bacterial communities of the gut, and differences in responses to vaccines is shown.”
“This study may give us fresh insights into the differences that we see in the amount of protective antibodies made after infant vaccination. It also gives us clues as to ways that we might be able to level the playing field for infants in the future – for instance, giving babies a safe cocktail of ‘friendly bacteria’ as a probiotic, or an additional dose of vaccine.”
“This study is the first step – it shows us a link or association but does not prove cause and effect that differences in the way babies are born alters how the immune system responds to vaccines. To prove this link we will need larger studies, but it is tantalizing data.”
The research was funded by Scotland’s Chief Scientist Office and the Netherlands Organisation for Scientific Research. DB received funding from OM pharma and Sanofi. All of the authors declared no other conflicts of interest.
A version of this article first appeared on Medscape.com.
Babies born vaginally have a different microbiome to those born by Caesarean section and have heightened responses to childhood vaccinations, according to a new study heralded as “interesting and important” by experts.
The microbiome is known to play a role in immune responses to vaccination. However, the relationship between early-life effects on intestinal microbiota composition and subsequent childhood vaccine responses had remained poorly understood. In the new study, “the findings suggest that vaginal birthing resulted in a microbiota composition associated with an increase in a specific type of antibody response to two routine childhood vaccines in healthy babies, compared with Caesarean section,” the authors said.
Researchers from the University of Edinburgh, with colleagues at Spaarne Hospital and University Medical Centre in Utrecht, and the National Institute for Public Health and the Environment in The Netherlands, tracked the development of the gut microbiome in a cohort of 120 healthy, full-term infants and assessed their antibody levels following two common childhood vaccinations.
The study, published in Nature Communications, found “a clear relationship between microbes in the gut of those babies and levels of antibodies.” Not only was vaginal birth associated with increased levels of Bifidobacterium and Escherichia coli in the gut microbiome in the first months of life but also with higher IgG antibody responses against both pneumococcal and meningococcal vaccines.
Antibody responses doubled after vaginal birth
The babies were given pneumococcal and meningococcal vaccinations at 8 and 12 weeks, and saliva was collected at follow-up visits at ages 12 and 18 months for antibody measurement. In the 101 babies tested for pneumococcal antibodies, the researchers found that antibody levels were twice as high among babies delivered naturally, compared with those delivered by C-section. High levels of two gut bacteria in particular – Bifidobacterium and E. coli – were associated with high antibody responses to the pneumococcal vaccine, showing that the microbiome mediated the link between mode of delivery and pneumococcal vaccine responses.
In 66 babies tested for anti-meningococcal antibodies, antibodies were 1.7 times higher for vaginally-born babies than those delivered via C-section, and high antibody levels were particularly associated with high levels of E. coli in the babies’ microbiome.
The results were also influenced by breast-feeding, which even among children born vaginally was linked with 3.5 times higher pneumococcal antibody levels, compared with those of formula-fed children. In contrast, levels of antibodies against meningococcus were unaffected by breast-feeding status.
Microbiome ‘sets level of infection protection’
The team said: “The baby acquires Bifidobacterium and E. coli bacteria through natural birth, and human milk is needed to provide the sugars for these bacteria to thrive on.” They explained: “The gut microbiome is seeded at birth, developing rapidly over the first few months of life, and is influenced mostly by delivery mode, breast-feeding, and antibiotic use.” The babies’ microbiome in early life contributes the immune system’s response to vaccines, they said, “and sets the level of protection against certain infections in childhood.”
Study lead Professor Debby Bogaert, chair of pediatric medicine at the University of Edinburgh, said: “I think it is especially interesting that we identified several beneficial microbes to be the link between mode of delivery and vaccine responses. In the future, we may be able to supplement those bacteria to children born by C-section shortly after birth through – for example, mother-to-baby ‘fecal transplants’ or the use of specifically designed probiotics.”
First author Dr. Emma de Koff, a microbiology trainee at the Amsterdam University Medical Center, said: “We expected to find a link between the gut microbiome and the babies’ vaccine responses, however we never thought to find the strongest effects in the first weeks of life.”
The findings “could help to inform conversations about C-sections between expectant mothers and their doctors,” commented the researchers, who said that they could also “shape the design of more tailored vaccination programs.” For example, in the future, vaccination schedules could be adjusted based on the method of delivery or analysis of the baby’s microbiome.
Potential to rectify immune system after Caesarean
Responding to the study, Professor Neil Mabbott, personal chair in immunopathology at the Roslin Institute of the University of Edinburgh, told the Science Media Centre: “This is a very interesting and important study. The authors show that infants delivered by a vaginal birth had higher responses to the two different types of vaccines against bacterial diseases, and this was associated with higher abundances of the potentially beneficial bacteria known as Bifidobacterium and E. coli in their intestines.”
He added: “This study raises the possibility that it may be possible to treat infants, especially Caesarean-delivered infants, with a bacterial supplement, or even a product produced by these beneficial bacteria, to help improve their immune systems, enhance their responses to certain vaccines and reduce their susceptibility to infections.”
The study raises important questions, he said, including whether the increased antibody levels from pneumococcal and meningococcal vaccinations following vaginal birth also leads to increased protection of the infants against infection or serious disease.
Sheena Cruickshank, immunologist and professor in biomedical sciences at the University of Manchester, England, commented: “It is now well established that the microbiome is important in immune development. In turn the mode of delivery and initial method of feeding is important in how the microbiome is first seeded in the baby.”
“However, other factors such as exposure to antibiotics and subsequent diet also play a role in how it then develops, making understanding the way the microbiome develops and changes quite complex. Microbes works as communities, and it can be difficult to determine whether changes in single species are important functionally. Breast milk also plays an important role in protecting the baby via transfer of maternal immunoglobulins, which will wane over a period of 6-12 months in the baby – thus ascertaining whether it’s the baby’s Ig is challenging.
“Given the complexity of the multitude of interactions, it is important that this is accounted for, and group sizes are large enough to ensure data is robust. Whilst this is an interesting study that adds to our knowledge of how the microbiome develops and the possible implications for immune development, it is still very preliminary, and the small group sizes warrant a need for further studies to verify this in larger groups.”
She added: “We will need to understand whether possible impacts of maternal delivery and feeding on immune development or vaccine responses can be restored by, for example, manipulating the microbiome.”
Professor Kim Barrett, vice dean for research at the University of California, Davis School of Medicine, said that, while further research was needed to uncover if and how manipulation of the human microbiome following C-section births might improve vaccine efficacy, “the work should at least lead to prompt additional consideration about an unintended consequence of the ever-increasing use of C-sections that may not be medically-necessary.”
Dr. Marie Lewis, researcher in gut microbiota at the University of Reading, England, said: “We have known for quite some time that the mode of delivery is incredibly important when it comes to the type of bacteria which colonize our guts. We also know that our gut bacteria in early life drive the development of our immune system, and natural births are linked with reduced risks of developing inflammatory conditions, such as asthma. It is therefore perhaps not really surprising that mode of delivery is also linked to responses to vaccinations.”
“The really interesting part here is the extent to which our gut microbiotas are accessible and changeable, and this important work could pave the way for administration of probiotics and prebiotics to improve vaccine responses in Caesarean-born children.”
‘Tantalizing data’
Dr. Chrissie Jones, associate professor of pediatric infectious diseases at the University of Southampton, and Southampton UK and education lead for the British Paediatric Allergy, Immunity, and Infection Group, said: “The link between method of delivery of the infant and the bacteria that live in the gut of the young infant has previously been shown. What is really interesting about this study is that, for the first time, the link between method of delivery (vaginal delivery vs. C-section), differences in bacterial communities of the gut, and differences in responses to vaccines is shown.”
“This study may give us fresh insights into the differences that we see in the amount of protective antibodies made after infant vaccination. It also gives us clues as to ways that we might be able to level the playing field for infants in the future – for instance, giving babies a safe cocktail of ‘friendly bacteria’ as a probiotic, or an additional dose of vaccine.”
“This study is the first step – it shows us a link or association but does not prove cause and effect that differences in the way babies are born alters how the immune system responds to vaccines. To prove this link we will need larger studies, but it is tantalizing data.”
The research was funded by Scotland’s Chief Scientist Office and the Netherlands Organisation for Scientific Research. DB received funding from OM pharma and Sanofi. All of the authors declared no other conflicts of interest.
A version of this article first appeared on Medscape.com.
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