Antibiotic treatment in malnourished children improves the development of intestinal microbiota | Washington University School of Medicine in St. Louis

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The study noted long-term benefits, encouraging monitoring of short-term risks

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Malnutrition threatens the lives of millions of children under 5 years old, causing about 500,000 deaths each year in low- and middle-income countries. Short courses of antibiotics combined with peanut butter-based therapeutic foods are the standard of care for treating severe acute malnutrition in children, but antibiotic use in vulnerable populations is This injury is controversial; Public health experts worry about the growing problem of antibiotic resistance.

Now, a new study led by Dr. Gautam Dantas at Washington University School of Medicine in St. Louis leads the way showing that concerns about increasing antibiotic resistance are valid but that the long-term benefits may outweigh the short-term risks. Findings published October 19 in The Lancet Microbe show a more mature, diverse gut microbiome in malnourished Nigerian children two years after antibiotic treatment. The brief increase in antibiotic resistance genes in gut bacteria after the children were treated completely disappeared within three weeks.

Antibiotics can disturb the microbiome and increase the risk of infection, which is a concern in children with impaired immunity, explains Dantas, study co-author and Conan Professor of Laboratory and Genomic Medicine. Reduced immunity and malnutrition make you susceptible to infection. But we show an improvement in microbiome maturation over many years after a short course of antibiotics compared with placebo, an important finding that suggests stunted microbiome development is involved. to adverse outcomes of malnutrition in malnourished children. This study provides evidence that although we should be careful in our use of antibiotics, the risk of increasing drug-resistant bacteria in the short term may be outweighed by the benefits of improving the microbiome. this permanent object.

Doctors who use antibiotics to treat severely malnourished children with infections also see another benefit: The children grow and gain muscle mass. That promising observation triggered a large-scale clinical trial conducted in Madarounfa, Niger. Led by Sheila Isanaka, ScD, associate professor of nutrition at the Harvard T.H. Chan School of Public Health, that trial demonstrated an increase in weight gain and body measurements in children who received antibiotics during their treatment. Treat severe acute malnutrition.

But the question remains: Does giving antibiotics to severely malnourished children promote antibiotic resistance? Isanaka proposed an additional substudy to examine antibiotic resistance in the gastrointestinal tract of antibiotic-treated children participating in a clinical trial in Niger.

Dantas’ team includes first author Drew J. Schwartz, MD, PhD, then a member of Dantas’ laboratory and now assistant professor of pediatrics, and Amy Langdon, PhD, a graduate student at Dantas’ laboratory at the time of the study analyzed, using fecal samples, the gut microbiota of 161 children randomly selected from a group of 2,399 severely malnourished Nigerian children participating Isanakas clinical trial. About half of the children received amoxicillin for one week; the other half received a placebo. All children receive treats made with therapeutic peanut butter. Stool samples were collected at the end of the seven-day treatment period and four, eight, and 12 weeks after enrollment.

Two years later, researchers followed 22 children who had been treated with antibiotics and 13 children who had received a placebo. They also analyzed stool samples from 38 children of similar ages who were not malnourished in Niger for comparison.

Researchers discovered a more diverse and rich microbiome in children two years after treatment with amoxicillin, when compared with those who received a placebo. The microbiota of children treated with antibiotics is mature, similar to that of healthy children of the same age.

Some of the key factors that promote robust maturation of the gut microbiome during the first three years of life include the infant’s exposure to maternal bacteria during and after birth, consumption of milk, and transition to solid foods. solid food. In malnourished children, the maturation of the intestinal microbiota is slowed along with growth. But adding antibiotics to the treatment plan improved body measurements and microbiome growth.

Antibiotics have the ability to act as a reset device, allowing the bacteria that help digest solid foods to thrive in the intestinal ecosystem. According to Dantas, who previously found that antibiotic use in premature infants has harmful and lasting effects, lasting improvements in the richness, diversity and maturity of the microbiome were observed. in the present study is surprising.

Dantas, who is also a professor of pathology & immunology, biomedical engineering, molecular microbiology and pediatrics, explains: There are examples of the gut microbiome not fully recovering from perturbation. serious. But our new study sheds light on the unexpected long-term collateral benefit of antibiotic treatment in severely malnourished children, which causes their gut microbiota to adopt a developmental trajectory. improved.

In the short term, researchers found that children treated with antibiotics had more bacteria, such as E coli And Klebsiella, which can cause serious infections. But that increase resolved within three weeks. Dantas warns that the rise of drug-resistant bacteria and drug-resistant genes in children treated with antibiotics should not be ignored.

Dantas warns: “We now know the benefits of antibiotic treatment appear to outweigh the risks in this particular population, but the risks still exist.” Until a better approach is found, we should use antibiotics to help children with severe acute malnutrition. But we should monitor these children for the increased risk of acquiring drug-resistant bacteria in the first weeks after antibiotic treatment. At the same time, we should put resources into developing new therapeutic approaches that do not severely impact the microbiome.

Schwartz DJ, Langdon A, Sun Madarounfa, Niger: retrospective metagenomic analysis of a placebo-controlled trial. Lancet bacteria. October 19, 2023.

Funding for this project was provided by the National Institute of General Medical Sciences, grant number R01 GM099538; National Institute of Allergy and Infectious Diseases grants R01 AI123394 and K08 AI1593834; Eunice Kennedy Shriver National Institute of Child Health and Human Development, grant number R01 HD092414; Edward Mallinckrodt Jr. Foundation; Bill & Melinda Gates Foundation Grand Challenge, GCE Phase I grant number OPP1161117; Doris Duke Charitable Foundation, grant number 2021081; NIH Clinical and Translational Fellowship Award, grant number TL1 TR00044. Funding for the parent trial was provided by the Operational Center Mdecins sans Frontires Paris (Doctors Without Borders).

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