Fecal transplants seem crucial to protect newborns after receiving antibiotics

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Less well known: the price some children seem to pay when the early use of powerful antibiotics disrupts their immune system development at a fundamental, potentially lifelong level. When given “just in case”, the cost of using antibiotics can be higher than many realize: children are unable to fight off pneumonia triggered by infection later in childhood, become more likely to develop asthma and other conditions that can become lifelong chronic health problems.

Cincinnati Children’s neonatologist and immunology expert Hitesh DeshmukhMD, PhD, has been studying this question for years. Now, his research team has completed another important study that documents why doctors should be concerned about near-occasional overuse of antibiotics. Details have been published online June 15, 2022in Science Translational Medicine.

“It is not possible to completely stop the use of antibiotics in newborns. In some cases, antibiotics are the only way to prevent death from infections like Group B Streptococcus“, says Deshmukh. “However, this article shows why the use of antibiotics must be reduced to an absolute minimum and why it is important to compensate for this use as soon as possible.”

Balancing the good against the bad in antibiotic treatment

About 1 in 4 pregnant women carry Ggroup B streptococcus (GBS) in their body without showing any obvious symptoms. Although these bacteria rarely cause serious problems in adults, infections can cause sepsis, pneumonia, and meningitis in newborns, all of which can be fatal without skilled hospital care.

In the United States, about 7,600 GBS infections in newborns occurred each year before widespread use of preventative antibiotics, according to the federal government’s Centers for Disease Control and Prevention. Since 1993, the rate of infections occurring during the first week after birth has decreased by approximately 87%, from 1.7 cases per 1,000 live births to 0.22 cases per 1,000 live births in 2016.

However, more than 2.4 million babies are born through vaginal birth in the United States each year. In the 1990s, up to half of these women received antibiotic treatment just in case. Since 2002, when testing for GBS became recommended practice, the use of preventive antibiotics has tightened.

Still, with up to 500,000 newborns a year in the United States exposed to immune system-disrupting antibiotics, Deshmukh says more attention needs to be paid to the large but unknown number of children suffering side effects. , including high risks of developing severe pneumonia. later in infancy and early childhood, as well as lifelong health problems like asthma.

Deep Relationship Between Gut Bacteria and Lung Development

A growing body of research, including work by experts at Cincinnati Children’s, has gradually uncovered how much the mix of bacteria and fungi that normally live in our intestines influences our health. In 2017, Deshmukh published resultsbased on mouse models, which demonstrated how antibiotics go far beyond killing “bad” bacteria to disrupt the still-developing immune system of newborns by killing “good” bacteria as well.

In this study, animals that were exposed to antibiotics as newborns and later exposed to bacteria known to trigger severe pneumonia were compared to animals that were not exposed to early antibiotic treatment. . All antibiotic-disturbed animals suffered severe symptoms within 60 hours. Everyone with an unimpaired immune system avoided severe symptoms.

This research has particularly delved into the molecular and genetic differences that occur between newborns who receive early antibiotic therapy and those who do not. The 17-member research team, led by Deshmukh and first author Joseph Steven, a graduate student in immunobiology, used single-cell RNA sequencing, flow cytometry, a growing atlas of genetic data called LungMAP, and other resources to analyze multiple types of immune cells in the lungs, as well as the complex mix of bacteria in the intestine. The study lasted two years.

The team identified a multitude of disturbances caused by antibiotic exposure in the quantity and structure of immune cells called neutrophils present in the blood and in lung tissue. They also documented damaged versions of other types of immune cells, including T cells, alveolar macrophages, and interstitial macrophages. All of these changes combined to produce a hyperinflammatory response in the lungs to infection in antibiotic-exposed newborns.

Some of these dysfunctional cells have already been found in human newborns who suffered severe pneumonia after various types of infections from which many other children recover easily.

These details will be important for scientists looking for ways to undo the damage antibiotic use can cause in newborns. For example, the co-authors say they found potential biomarkers, or molecular signatures, that could quickly reveal which children are most at risk of developing severe pneumonia. This could allow clinicians to intervene more aggressively with these children in the event of an infection.

Ultimately, this line of work may lead to more precise use of antibiotics, redesigned antibiotics that harm “good” bacteria less, and supportive treatments to restore a healthy gut microbiota when potent antibiotic treatment is needed.

“The body moves quickly after birth to fully establish the immune protection system of the lungs,” says Deshmukh. “Failure to restore a healthy gut microbiota before this developmental window closes may result in infants growing up with lungs that are permanently less able to respond to infections later in life.”

More Science Behind Fecal Transplantation

The good news from the latest findings is that the damage caused by antibiotics to the commensal microbiota can be restored by transferring a supply of healthy bacteria to the intestines of a child who is lacking them – a process called fecal transplantation.

In this study, fecal transplants completely restored commensal bacteria to normal pre-exposure levels in some animals that had suffered early antibiotic damage, but only partially in others. Those with restored and partially restored gut microbiota developed stronger immune systems in their lungs and were better able to withstand the “challenge” of the infection causing pneumonia.

Several scenarios may explain this partial restoration, the co-authors wrote. But more research is needed to confirm which possibilities are the most accurate explanation.

What’s the takeaway for families?

It may take years for faecal transplantation to become standard practice in newborn care, if future human studies prove that such transplants are necessary. In the meantime, what should families do to minimize the potential long-term health risks to their child that could be related to a birth dose of antibiotics?

First, Deshmukh says parents should ask questions until they’re convinced they understand why the doctor is recommending the antibiotic. These drugs are still very necessary to treat serious, life-threatening infections.

Currently, fecal transplantation is being studied in a number of clinical trials nationwide, but primarily as a supportive therapy for people receiving gut-disruptive treatments, such as stem cell transplants for the cancer. So far a small study published in 2020 by scientists from Denmark found that faecal transplantation from mother to child after cesarean section quickly brought the newborn’s gut microbiota to match that of its mother.

Deshmukh says Cincinnati Children’s does not perform fecal transplants for otherwise healthy newborns, even in clinical trials, and he is not aware of other hospitals doing so.

It may also be possible to rebalance a child’s commensal bacteria in a healthy way through other methods, such as adding molecules made by normal, healthy microbiota. However, further work is needed to identify the specific actors needed for these more targeted strategies. Currently, the most useful long-term way to reduce the risk of contracting a dangerous infection that can lead to pneumonia is to ensure that children and adults receive all the vaccines to which they are entitled.

Next steps

Further study is still needed to fully translate animal-based findings into practice changes among neonatologists, new tests or improved antibiotics. Beyond full fecal transplants that transfer a small amount of each insect into a healthy gut, researchers also hope to determine which types of bacteria are most important for the transfers.

“Our study lacked the power to establish a clear association between specific bacterial taxa and clinical response to pneumonia,” the co-authors state.

Further studies are also needed to determine what impact, if any, breast milk has on immune protection amid the chaos triggered by antibiotic exposure. Breast milk is known to provide considerable immune protection to newborns through super antibodies produced by mothers, but it is unclear to what extent this benefit outweighs the disruption triggered by early antibiotics. All animals were formula fed in this study.

About this study

Funding for this research (DOI number: 10.1126/scitranslmed.abl3981) includes several grants from the National Institutes of Health supporting co-authors and core laboratory resources (HD084686, HL155611, ES029234, HL142708, ES029234, AG053498, HD028827, HL149366, AI152100, CA226802, HL148865, HD89939, EB029863, GM128452, AI138553, HL142485 , AI157626, AI150554, P51 OD11107, OD27094, U01HL134745 and U01HL122642)

The authors declare that they have no competing interests.

SOURCE Cincinnati Children’s Hospital Medical Center

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