Dataset Information

Gut Microbial Diversity in Antibiotic-Naive Children After Systemic Antibiotic Exposure: A Randomized Controlled Trial.

ABSTRACT: Antibiotic exposure can alter the gut microbiome. We evaluate the effects of azithromycin on the gut microbiome diversity of children from an antibiotic-naive community in Niger.A population-based sample of 80 children aged 1-60 months in the Dosso region of Niger was randomized to receive a single dose of either oral azithromycin or placebo. Fecal samples were collected immediately before treatment and 5 days after treatment for 16S rRNA gene sequencing. The prespecified outcome was ?-diversity (inverse Simpson's ?-diversity index), with secondary outcomes of ? and ? Simpson's and Shannon's diversities.At 5 days after treatment, 40 children aged 1-60 months were analyzed in the azithromycin-treated group and 40 children in the placebo-treated group. Diversity of the gut microbiome was significantly lower in the treated group (inverse Simpson's ?-diversity, 5.03; 95% confidence interval [CI], 4.08-6.14) than in the placebo group (6.91; 95% CI, 5.82-8.21; P = .03). Similarly, the Shannon's ?-diversity was lower in the treated group (10.60; 95% CI, 8.82-12.36) than the placebo group (15.42; 95% CI, 13.24-17.80; P = .004). Simpson's community-level (?) diversity decreased with azithromycin exposure from 17.72 (95% CI, 13.80-20.21) to 10.10 (95% CI, 7.80-11.40; P = .00008), although ?-diversity was not significantly reduced (2.56, 95% CI, 1.88-3.12; to 2.01, 95% CI, 1.46-2.51; P = .26).Oral administration of azithromycin definitively decreases the diversity of the gut microbiome of children in an antibiotic-naive community.NCT02048007.

SUBMITTER: Doan T

PROVIDER: S-EPMC5849050 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Gut Microbial Diversity in Antibiotic-Naive Children After Systemic Antibiotic Exposure: A Randomized Controlled Trial.

Doan Thuy T Arzika Ahmed M AM Ray Kathryn J KJ Cotter Sun Y SY Kim Jessica J Maliki Ramatou R Zhong Lina L Zhou Zhaoxia Z Porco Travis C TC Vanderschelden Benjamin B Keenan Jeremy D JD Lietman Thomas M TM

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20170501 9

<h4>Background</h4>Antibiotic exposure can alter the gut microbiome. We evaluate the effects of azithromycin on the gut microbiome diversity of children from an antibiotic-naive community in Niger.<h4>Methods</h4>A population-based sample of 80 children aged 1-60 months in the Dosso region of Niger was randomized to receive a single dose of either oral azithromycin or placebo. Fecal samples were collected immediately before treatment and 5 days after treatment for 16S rRNA gene sequencing. The p ...[more]

PMID: 28402408

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Project description:The microbiota in the human gastrointestinal tract (GIT) is highly exposed to antibiotics, and may be an important reservoir of resistant strains and transferable resistance genes. Maternal GIT strains can be transmitted to the offspring, and resistances could be acquired from birth. This is a case study using a metagenomic approach to determine the diversity of microorganisms conferring tetracycline resistance (Tc(r)) in the guts of a healthy mother-infant pair one month after childbirth, and to investigate the potential for horizontal transfer and maternal transmission of Tc(r) genes. Fecal fosmid libraries were functionally screened for Tc(r), and further PCR-screened for specific Tc(r) genes. Tc(r) fosmid inserts were sequenced at both ends to establish bacterial diversity. Mother and infant libraries contained Tc(r), although encoded by different genes and organisms. Tc(r) organisms in the mother consisted mainly of Firmicutes and Bacteroidetes, and the main gene detected was tet(O), although tet(W) and tet(X) were also found. Identical Tc(r) gene sequences were present in different bacterial families and even phyla, which may indicate horizontal transfer within the maternal GIT. In the infant library, Tc(r) was present exclusively in streptococci carrying tet(M), tet(L) and erm(T) within a novel composite transposon, Tn6079. This transposon belongs to a family of broad host range conjugative elements, implying a potential for the joint spread of tetracycline and erythromycin resistance within the infant's gut. In addition, although not found in the infant metagenomic library, tet(O) and tet(W) could be detected in the uncloned DNA purified from the infant fecal sample. This is the first study to reveal the diversity of Tc(r) bacteria in the human gut, to detect a likely transmission of antibiotic resistance from mother to infant GITs and to indicate the possible occurrence of gene transfers among distantly related bacteria coinhabiting the GIT of the same individual.

Project description:BackgroundAcquisition of the intestinal microbiota in early life corresponds with the development of the mucosal immune system. Recent work on caesarean-delivered infants revealed that early microbial composition is influenced by birthing method and environment. Furthermore, we have confirmed that early-life environment strongly influences both the adult gut microbiota and development of the gut immune system. Here, we address the impact of limiting microbial exposure after initial colonization on the development of adult gut immunity.Methodology/principal findingsPiglets were born in indoor or outdoor rearing units, allowing natural colonization in the immediate period after birth, prior to transfer to high-health status isolators. Strikingly, gut closure and morphological development were strongly affected by isolator-rearing, independent of indoor or outdoor origins of piglets. Isolator-reared animals showed extensive vacuolation and disorganization of the gut epithelium, inferring that normal gut closure requires maturation factors present in maternal milk. Although morphological maturation and gut closure were delayed in isolator-reared animals, these hard-wired events occurred later in development. Type I IFN, IL-22, IL-23 and Th17 pathways were increased in indoor-isolator compared to outdoor-isolator animals during early life, indicating greater immune activation in pigs originating from indoor environments reflecting differences in the early microbiota. This difference was less apparent later in development due to enhanced immune activation and convergence of the microbiota in all isolator-reared animals. This correlated with elevation of Type I IFN pathways in both groups, although T cell pathways were still more affected in indoor-reared animals.Conclusions/significanceEnvironmental factors, in particular microbial exposure, influence expression of a large number of immune-related genes. However, the homeostatic effects of microbial colonization in outdoor environments require sustained microbial exposure throughout development. Gut development in high-hygiene environments negatively impacts on normal succession of the gut microbiota and promotes innate immune activation which may impair immune homeostasis.

Dataset Information

Gut Microbial Diversity in Antibiotic-Naive Children After Systemic Antibiotic Exposure: A Randomized Controlled Trial.

Publications

Gut Microbial Diversity in Antibiotic-Naive Children After Systemic Antibiotic Exposure: A Randomized Controlled Trial.

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