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Naturalization of the microbiota developmental trajectory of Cesarean-born neonates after vaginal seeding.
Song, SJ, Wang, J, Martino, C, Jiang, L, Thompson, WK, Shenhav, L, McDonald, D, Marotz, C, Harris, PR, Hernandez, CD, et al
Med (New York, N.Y.). 2021;2(8):951-964.e5
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Studies on model organisms show that foetal development can be modulated by microbial products from the pregnant mother’s microbiota, and early colonisation is critical for immune system development. However, natural transmission and colonisation of maternal microbes is impaired by caesarean section (CS) delivery. The aim of this study was to determine the effect of restoring exposure to maternal vaginal fluids after CS birth. This study is a large observational study of 177 infants born to 174 mothers. Physicians assessed healthy mothers who were set to deliver vaginally or by scheduled CS. Results demonstrate that microbial differences associated with delivery mode can be reduced by exposure to a vaginal microbial source at birth. In fact, birth mode significantly differentiated infant gut and skin microbiome development, and that seeding worked to adjust the trajectory of CS-delivered infants through partial restoration of microbiome features associated with a vaginal delivery. Authors conclude that restoring natural exposures at birth may be one way to reduce the risk of CS-associated diseases such as obesity, asthma, allergies, and immune disfunctions. However, randomised clinical trials on large cohorts are needed to gain conclusive evidence for microbial restoration at birth improving health outcomes.
Abstract
BACKGROUND Early microbiota perturbations are associated with disorders that involve immunological underpinnings. Cesarean section (CS)-born babies show altered microbiota development in relation to babies born vaginally. Here we present the first statistically powered longitudinal study to determine the effect of restoring exposure to maternal vaginal fluids after CS birth. METHODS Using 16S rRNA gene sequencing, we followed the microbial trajectories of multiple body sites in 177 babies over the first year of life; 98 were born vaginally, and 79 were born by CS, of whom 30 were swabbed with a maternal vaginal gauze right after birth. FINDINGS Compositional tensor factorization analysis confirmed that microbiota trajectories of exposed CS-born babies aligned more closely with that of vaginally born babies. Interestingly, the majority of amplicon sequence variants from maternal vaginal microbiomes on the day of birth were shared with other maternal sites, in contrast to non-pregnant women from the Human Microbiome Project (HMP) study. CONCLUSIONS The results of this observational study prompt urgent randomized clinical trials to test whether microbial restoration reduces the increased disease risk associated with CS birth and the underlying mechanisms. It also provides evidence of the pluripotential nature of maternal vaginal fluids to provide pioneer bacterial colonizers for the newborn body sites. This is the first study showing long-term naturalization of the microbiota of CS-born infants by restoring microbial exposure at birth. FUNDING C&D, Emch Fund, CIFAR, Chilean CONICYT and SOCHIPE, Norwegian Institute of Public Health, Emerald Foundation, NIH, National Institute of Justice, Janssen.
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Association between duration of intravenous antibiotic administration and early-life microbiota development in late-preterm infants.
Zwittink, RD, Renes, IB, van Lingen, RA, van Zoeren-Grobben, D, Konstanti, P, Norbruis, OF, Martin, R, Groot Jebbink, LJM, Knol, J, Belzer, C
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 2018;37(3):475-483
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Premature newborn babies are commonly given antibiotics in hospital to prevent or treat infections such as sepsis. This study, carried out in the Netherlands, looked at the effect of intravenous antibiotics on the development of the gut bacteria in premature babies. Stool samples were taken from 15 premature babies who had been exposed to either no antibiotic treatment, or short (less than 3 days) or long (at least 5 days) treatment with the commonly prescribed antibiotics amoxicillin or ceftazidime. At 3 weeks old, babies who had been treated with both short and long courses of antibiotics had significantly lower abundance of the beneficial bacteria Bifidobacterium than those who had received no antibiotics. In babies who received antibiotic treatment lasting 5 days or more, Bifidobacterium levels didn’t recover until they were 6 weeks old. Antibiotics were effective against Enterobacteriaceae, but allowed Enterococcus to thrive and remain dominant for up to two weeks after antibiotic treatment was stopped. The authors concluded that intravenous antibiotics during the first week of a baby’s life greatly affects the gut bacteria. However, short courses of antibiotics allow for a quicker recovery compared to longer courses. Disturbances in the development of gut bacteria caused by antibiotic treatment could influence the development of infants' immune and digestive systems.
Abstract
Antibiotic treatment is common practice in the neonatal ward for the prevention and treatment of sepsis, which is one of the leading causes of mortality and morbidity in preterm infants. Although the effect of antibiotic treatment on microbiota development is well recognised, little attention has been paid to treatment duration. We studied the effect of short and long intravenous antibiotic administration on intestinal microbiota development in preterm infants. Faecal samples from 15 preterm infants (35 ± 1 weeks gestation and 2871 ± 260 g birth weight) exposed to no, short (≤ 3 days) or long (≥ 5 days) treatment with amoxicillin/ceftazidime were collected during the first six postnatal weeks. Microbiota composition was determined through 16S rRNA gene sequencing and by quantitative polymerase chain reaction (qPCR). Short and long antibiotic treat ment significantly lowered the abundance of Bifidobacterium right after treatment (p = 0.027) till postnatal week three (p = 0.028). Long treatment caused Bifidobacterium abundance to remain decreased till postnatal week six (p = 0.009). Antibiotic treatment was effective against members of the Enterobacteriaceae family, but allowed Enterococcus to thrive and remain dominant for up to two weeks after antibiotic treatment discontinuation. Community richness and diversity were not affected by antibiotic treatment, but were positively associated with postnatal age (p < 0.023) and with abundance of Bifidobacterium (p = 0.003). Intravenous antibiotic administration during the first postnatal week greatly affects the infant's gastrointestinal microbiota. However, quick antibiotic treatment cessation allows for its recovery. Disturbances in microbiota development caused by short and, more extensively, by long antibiotic treatment could affect healthy development of the infant via interference with maturation of the immune system and gastrointestinal tract.