A history of repeated antibiotic usage leads to microbiota-dependent mucus defects
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Krigul KL, Feeney RH, Wongkuna S, Aasmets O, Holmberg SM, Andreson R, Puértolas-Balint F, Pantiukh K, Sootak L, Org T, Tenson T, Org E, Schroeder BO
Journal
Gut microbes
Year
2024
Keywords:
Akkermansia, Antibiotics, colonic mucosa, fecal microbiota transplantation, gut microbiome, intestinal barrier, mucus, short-chain fatty acids
Recent evidence indicates that repeated antibiotic usage lowers microbial diversity and ultimately changes the gut microbiota community. However, the physiological effects of repeated - but not recent - antibiotic usage on microbiota-mediated mucosal barrier function are largely unknown. By selecting human individuals from the deeply phenotyped Estonian Microbiome Cohort (EstMB), we here utilized human-to-mouse fecal microbiota transplantation to explore long-term impacts of repeated antibiotic use on intestinal mucus function. While a healthy mucus layer protects the intestinal epithelium against infection and inflammation, using ex vivo mucus function analyses of viable colonic tissue explants, we show that microbiota from humans with a history of repeated antibiotic use causes reduced mucus growth rate and increased mucus penetrability compared to healthy controls in the transplanted mice. Moreover, shotgun metagenomic sequencing identified a significantly altered microbiota composition in the antibiotic-shaped microbial community, with known mucus-utilizing bacteria, including Akkermansia muciniphila and Bacteroides fragilis, dominating in the gut. The altered microbiota composition was further characterized by a distinct metabolite profile, which may be caused by differential mucus degradation capacity. Consequently, our proof-of-concept study suggests that long-term antibiotic use in humans can result in an altered microbial community that has reduced capacity to maintain proper mucus function in the gut.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2024-12-20
Subjects
- Location of subjects
- Estonia
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Homo sapiens
- 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
- Response to antibiotic Response to antibiotic,response to antibiotic
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- hCTRL (No antibiotic use humans)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- hABX (Repeated antibiotic use humans)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Human adults who had not taken any antibiotics in the 6 months prior to stool sample collection but had used antibiotics at least 5 times within the last 5 years.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 4
- Group 1 sample size Number of subjects in the case (exposed) group
- 4
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Control group (hCTRL) = 10 years. Repeated antibiotics use (hABX) = 6 months.
Lab analysis
- Sequencing type
- WMS
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Statistical test
- ANCOM
- 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)?
- Yes
- Matched on Factors on which subjects have been matched on in a case-control study
- age, body mass index, diet, sex, Matched on: "Bristol stool scale" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.Bristol stool scale
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- decreased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-12-20
Source: Supplementary table 4
Description: ANCOM-BC differential analysis of gut microbial composition at genus level between hABX and hCTRL samples including those with a mean relative abundance below 1%.
Abundance in Group 1: increased abundance in hABX (Repeated antibiotic use humans)
Revision editor(s): YokoC
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-12-20
Source: Supplementary table 4
Description: ANCOM-BC differential analysis of gut microbial composition at genus level between hABX and hCTRL samples including those with a mean relative abundance below 1%.
Abundance in Group 1: decreased abundance in hABX (Repeated antibiotic use humans)
| NCBI | Quality Control | Links |
|---|---|---|
| Butyricicoccus | ||
| Escherichia | ||
| unclassified Bacillati | ||
| unclassified Clostridiaceae | ||
| unclassified Mycoplasmatota | ||
| unclassified Oscillospiraceae | ||
| unclassified Sphingomonadaceae |
Revision editor(s): YokoC
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2024-12-20
Differences from previous experiment shown
Subjects
- 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
- Colon Hindgut,Large bowel,Posterior intestine,Colon,colon
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Response to transplant Response to transplant,response to transplant
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- FMT-C (control transplant mice)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- FMT- ABX (antibiotic transplant mice)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Mice that received a fecal microbiota transplant (FMT) from the hABX (humans with a history of repeated antibiotic used) pool.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 8
- Group 1 sample size Number of subjects in the case (exposed) group
- 8
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Not specified
Lab analysis
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- centered log-ratio
- Statistical test
- Not specified
- Matched on Factors on which subjects have been matched on in a case-control study
- Not specified
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-12-20
Source: Figure 4e
Description: Boxplots of significant differentially abundant species (using ALDEX) in the distal colon of mouse microbiota between FMT-C and FMT-ABX, with at least a 0.1% mean relative abundance in either group.
Abundance in Group 1: increased abundance in FMT- ABX (antibiotic transplant mice)
Revision editor(s): YokoC
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-12-20
Source: Figure 4e
Description: Boxplots of significant differentially abundant species (using ALDEX) in the distal colon of mouse microbiota between FMT-C and FMT-ABX, with at least a 0.1% mean relative abundance in either group.
Abundance in Group 1: decreased abundance in FMT- ABX (antibiotic transplant mice)
Revision editor(s): YokoC
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