Antibiotics in early life alter the gut microbiome and increase disease incidence in a spontaneous mouse model of autoimmune insulin-dependent diabetes

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Candon S, Perez-Arroyo A, Marquet C, Valette F, Foray AP, Pelletier B, Milani C, Ventura M, Bach JF, Chatenoud L
Journal
PloS one
Year
2015
Insulin-dependent or type 1 diabetes is a prototypic autoimmune disease whose incidence steadily increased over the past decades in industrialized countries. Recent evidence suggests the importance of the gut microbiota to explain this trend. Here, non-obese diabetic (NOD) mice that spontaneously develop autoimmune type 1 diabetes were treated with different antibiotics to explore the influence of a targeted intestinal dysbiosis in the progression of the disease. A mixture of wide spectrum antibiotics (i.e. streptomycin, colistin and ampicillin) or vancomycin alone were administered orally from the moment of conception, treating breeding pairs, and during the postnatal and adult life until the end of follow-up at 40 weeks. Diabetes incidence significantly and similarly increased in male mice following treatment with these two antibiotic regimens. In NOD females a slight yet not significant trend towards an increase in disease incidence was observed. Changes in gut microbiota composition were assessed by sequencing the V3 region of bacterial 16S rRNA genes. Administration of the antibiotic mixture resulted in near complete ablation of the gut microbiota. Vancomycin treatment led to increased Escherichia, Lactobacillus and Sutterella genera and decreased members of the Clostridiales order and Lachnospiraceae, Prevotellaceae and Rikenellaceae families, as compared to control mice. Massive elimination of IL-17-producing cells, both CD4+TCRαβ+ and TCRγδ+ T cells was observed in the lamina propria of the ileum and the colon of vancomycin-treated mice. These results show that a directed even partial ablation of the gut microbiota, as induced by vancomycin, significantly increases type 1 diabetes incidence in male NOD mice thus prompting for caution in the use of antibiotics in pregnant women and newborns.

Experiment 1


Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Subjects

Location of subjects
France
Host species Species from which microbiome was sampled. Contact us to have more species added.
Mus musculus
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Control group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Vancomycin treated group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Feces samples were collected from 8-week-old mice treated with vancomycin.
Group 0 sample size Number of subjects in the control (unexposed) group
13
Group 1 sample size Number of subjects in the case (exposed) group
6

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Ion Torrent

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
Mann-Whitney (Wilcoxon)
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased

Signature 1

Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Source: Figure 4a

Description: Variation of bacterial taxa at genus level when mice are treated with vancomycin.

Abundance in Group 1: increased abundance in Vancomycin treated group

NCBI Quality ControlLinks
Anaeroplasma
Escherichia
Lactobacillus
Sutterella
unclassified Bacteria
unclassified Enterobacteriaceae
unclassified Muribaculaceae
Mucispirillum

Revision editor(s): Aleru Divine, WikiWorks

Signature 2

Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Source: Figure 4a

Description: Variation of bacterial taxa at genus level when mice are treated with vancomycin.

Abundance in Group 1: decreased abundance in Vancomycin treated group

NCBI Quality ControlLinks
Bacteroides
Oscillospira
Prevotella
unclassified Bacteroidales
unclassified Eubacteriales
unclassified Lachnospiraceae
unclassified Prevotellaceae
unclassified Rikenellaceae

Revision editor(s): Aleru Divine, WikiWorks

Experiment 2


Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Strep-Col-Amp treated group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Feces samples were collected from 8-week-old mice treated with streptomycin, colistin and ampicillin.
Group 1 sample size Number of subjects in the case (exposed) group
7

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased

Signature 1

Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Source: Figure 4b

Description: Variation of bacterial taxa at genus level when mice are treated with streptomycin, colistin and ampicillin.

Abundance in Group 1: increased abundance in Strep-Col-Amp treated group

NCBI Quality ControlLinks
Akkermansia
Bacteroides
Bifidobacterium
Burkholderia
Dialister
Enterobacter
Erwinia
Escherichia
Faecalibacterium
Lachnospira
Lactobacillus
Methylobacterium
Oscillospira
Roseateles
Prevotella
Propionibacterium
Pseudomonas
Ralstonia
Sutterella
unclassified Bacteria
unclassified Enterobacteriaceae
unclassified Microbacteriaceae
unclassified Oxalobacteraceae
unclassified Sphingomonadaceae

Revision editor(s): Aleru Divine, WikiWorks

Signature 2

Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Source: Figure 4b

Description: Variation of bacterial taxa at genus level when mice are treated with streptomycin, colistin and ampicillin.

Abundance in Group 1: decreased abundance in Strep-Col-Amp treated group

NCBI Quality ControlLinks
Prevotella
unclassified Bacteroidales
unclassified Eubacteriales
unclassified Lachnospiraceae
unclassified Prevotellaceae
unclassified Rikenellaceae
unclassified Muribaculaceae

Revision editor(s): Aleru Divine, WikiWorks