Dataset Information

Structural and Functional Alterations in the Microbial Community and Immunological Consequences in a Mouse Model of Antibiotic-Induced Dysbiosis.

ABSTRACT: The aim of this study was to establish continuous therapeutic-dose ampicillin (CTDA)-induced dysbiosis in a mouse model, mimicking typical adult exposure, with a view to using this to assess its impact on gut microbiota, intestinal metabolites and host immune responses. Mice were exposed to ampicillin for 14 days and antibiotic-induced dysbiosis was evaluated by alteration of microbiota and gut permeability. The cecal index was increased in the CTDA group, and the gut permeability indicated by fluorescent dextran, endotoxin and D-Lactate in the serum was significantly increased after antibiotic use. The tight-junction proteins ZO-1 and occludin in the colon were reduced to half the control level in CTDA. We found that alpha-diversity was significantly decreased in mice receiving CTDA, and microbial community structure was altered compared with the control. Key taxa were identified as CTDA-specific, and the relative abundance of Enterococcus and Klebsiella was particularly enriched while Lachnospiraceae, Coprobacillus and Dorea were depleted after antibiotic treatment. In particular, a significant increase in succinate and a reduction in butyrate was detected in CTDA mice, and the triggering of NF-?B enhancement reflected that the host immune response was influenced by ampicillin use. The observed perturbation of the microbiota was accompanied by modulation of inflammatory state; this included increase in interferon-? and RegIII?, and a decrease in secretory IgA in the colon mucosa. This study allowed us to identify the key taxa associated with an ampicillin-induced state of dysbiosis in mice and to characterize the microbial communities via molecular profiling. Thus, this work describes the bacterial ecology of antibiotic exposure model in combination with host physiological characteristics at a detailed level of microbial taxa.

SUBMITTER: Shi Y

PROVIDER: S-EPMC6110884 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Structural and Functional Alterations in the Microbial Community and Immunological Consequences in a Mouse Model of Antibiotic-Induced Dysbiosis.

Shi Ying Y Kellingray Lee L Zhai Qixiao Q Gall Gwenaelle Le GL Narbad Arjan A Zhao Jianxin J Zhang Hao H Chen Wei W

Frontiers in microbiology 20180821

The aim of this study was to establish continuous therapeutic-dose ampicillin (CTDA)-induced dysbiosis in a mouse model, mimicking typical adult exposure, with a view to using this to assess its impact on gut microbiota, intestinal metabolites and host immune responses. Mice were exposed to ampicillin for 14 days and antibiotic-induced dysbiosis was evaluated by alteration of microbiota and gut permeability. The cecal index was increased in the CTDA group, and the gut permeability indicated by f ...[more]

PMID: 30186263

Similar Datasets

Project description:Pioneer microbiota colonizing the newborn gastrointestinal tract has long-lasting effects on host health. Restoration of the gut microbial community, following dysbiosis during the neonatal period, may be one strategy to prevent undesirable health outcomes linked to an altered neonatal gut microbiome. Without appropriate animal models that recreate the prolonged human neonatal developmental period it is not possible to effectively analyze interventions designed to restore regional microbial populations. Our study used a lamb model in which intestinal segments were surgically isolated (blind-ended) in fetal lambs to create early microbial dysbiosis by delaying post-natal exposure to intestinal ingesta. Intestinal segments isolated in utero retained blood flow, innervation, and lymphatic drainage through the mesenteric attachment. Continuity of the fetal gastro-intestinal tract was re-established by side-to-side anastomosis of intestine proximal and distal to each isolated intestinal segment. Microbial restoration was then implemented in neonatal lambs by reconnecting a portion of the in utero isolated intestinal segments to adjacent intestinal tract 1 and 7 days after birth. Bacterial communities colonizing the adjacent intestine, in utero isolated intestinal segments, and reconnected intestinal segments were profiled using 16S amplicon sequencing on days 1, 7, and 56 of age. The in utero isolated intestinal segments were colonized 1 day after birth but the density of active bacteria was reduced and community composition altered when compared to adjacent intestine. Proteobacteria dominated the adjacent small intestine at early time points (day 1 and day 7) with a shift to primarily Firmicutes on day 56, consistent with establishment of an anaerobic bacterial community. In contrast, Proteobacteria persisted as the predominant community for 56 days in the in utero isolated intestinal segments. There was, however, almost full restoration of the microbial community composition in the in utero isolated intestinal segments following reconnection to the adjacent intestine. The density of beneficial bacteria, especially Bifidobacterium, remained significantly lower in the reconnected intestinal segments at 56 days when compared to adjacent intestine. Post-natal persistence of a stable pioneer community (Proteobacteria) in the in utero isolated intestinal segments provides a model system to study the temporal effects of regional microbial dysbiosis throughout a prolonged neonatal period.

Dataset Information

Structural and Functional Alterations in the Microbial Community and Immunological Consequences in a Mouse Model of Antibiotic-Induced Dysbiosis.

Publications

Structural and Functional Alterations in the Microbial Community and Immunological Consequences in a Mouse Model of Antibiotic-Induced Dysbiosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets