Antibiotic treatment using amoxicillin-clavulanic acid impairs gut mycobiota development through modification of the bacterial ecosystem

Study information

Reviewed Marked as Reviewed by Folakunmi on 2024-1-15

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

37032359

DOI Digital object identifier for electronic documents.

10.1186/s40168-023-01516-y

URI

Authors

Spatz M, Da Costa G, Ventin-Holmberg R, Planchais J, Michaudel C, Wang Y, Danne C, Lapiere A, Michel ML, Kolho KL, Langella P, Sokol H, Richard ML

Journal

Microbiome

Year

2023

Keywords:

Antibiotics, Enterobacteriaceae, Microbiota, Mycobiota

BACKGROUND: Effects of antibiotics on gut bacteria have been widely studied, but very little is known about the consequences of such treatments on the fungal microbiota (mycobiota). It is commonly believed that fungal load increases in the gastrointestinal tract following antibiotic treatment, but better characterization is clearly needed of how antibiotics directly or indirectly affect the mycobiota and thus the entire microbiota. DESIGN: We used samples from humans (infant cohort) and mice (conventional and human microbiota-associated mice) to study the consequences of antibiotic treatment (amoxicillin-clavulanic acid) on the intestinal microbiota. Bacterial and fungal communities were subjected to qPCR or 16S and ITS2 amplicon-based sequencing for microbiota analysis. In vitro assays further characterized bacterial-fungal interactions, with mixed cultures between specific bacteria and fungi. RESULTS: Amoxicillin-clavulanic acid treatment triggered a decrease in the total fungal population in mouse feces, while other antibiotics had opposite effects on the fungal load. This decrease is accompanied by a total remodelling of the fungal population with the enrichment in Aspergillus, Cladosporium, and Valsa genera. In the presence of amoxicillin-clavulanic acid, microbiota analysis showed a remodeling of bacterial microbiota with an increase in specific bacteria belonging to the Enterobacteriaceae. Using in vitro assays, we isolated different Enterobacteriaceae species and explored their effect on different fungal strains. We showed that Enterobacter hormaechei was able to reduce the fungal population in vitro and in vivo through yet unknown mechanisms. CONCLUSIONS: Bacteria and fungi have strong interactions within the microbiota; hence, the perturbation initiated by an antibiotic treatment targeting the bacterial community can have complex consequences and can induce opposite alterations of the mycobiota. Interestingly, amoxicillin-clavulanic acid treatment has a deleterious effect on the fungal community, which may have been partially due to the overgrowth of specific bacterial strains with inhibiting or competing effects on fungi. This study provides new insights into the interactions between fungi and bacteria of the intestinal microbiota and might offer new strategies to modulate gut microbiota equilibrium. Video Abstract.

Experiment 1

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Reviewed Marked as Reviewed by Folakunmi on 2024-1-15

Curated date: 2023/10/10

Curator: Hodan Issah

Revision editor(s): Hodan Issah, LGeistlinger, MyleeeA, Folakunmi

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: Antimicrobial agent , Amoxicillin antibiotic,antibiotics,Antibiotika,Antibiotikum,antibiotique,antimicrobial,antimicrobial agents,microbicide,microbicides,Antimicrobial agent,antimicrobial agent,(2S,5R,6R)-6-,6-(p-hydroxy-alpha-aminophenylacetamido)penicillanic acid,6beta-[(2R)-2-amino-2-(4-hydroxyphenyl)acetamido]-2,2-dimethylpenam-3alpha-carboxylic acid,[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)[C@H](N)c1ccc(O)cc1)C(O)=O,alpha-amino-p-hydroxybenzylpenicillin,Amolin,Amopenixin,amoxicilina,Amoxicillin anhydrous,amoxicilline,amoxicillinum,amoxycillin,AMPC,AX,C16H19N3O5S,Clamoxyl,InChIKey=LSQZJLSUYDQPKJ-VLWBPTPADT,Moxal,p-hydroxyampicillin,Amoxicillin,amoxicillin

Group 0 name Corresponds to the control (unexposed) group for case-control studies: mouse before antibiotic treatment

Group 1 name Corresponds to the case (exposed) group for case-control studies: mouse after antibiotic treatment

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Mouse sample fungal results post-antibiotic treatment using Amoxicillin/clavulanate acid

Group 0 sample size Number of subjects in the control (unexposed) group: 7

Group 1 sample size Number of subjects in the case (exposed) group: 12

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): NA

Lab analysis

Sequencing type: ITS / ITS2

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: raw counts

Statistical test: DESeq2

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: increased

Signature 2

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Curated date: 2023/10/13

Curator: Hodan Issah

Revision editor(s): Hodan Issah

Source: figure 2D

Description: Amoxicillin/clavulanate acid treatment alters the fungal microbiota

Abundance in Group 1: increased abundance in mouse after antibiotic treatment

NCBI	Quality Control	Links
Aspergillus
Cladosporium
Valsa

Revision editor(s): Hodan Issah

Experiment 2

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Reviewed Marked as Reviewed by Folakunmi on 2024-1-15

Curated date: 2023/10/13

Curator: Hodan Issah

Revision editor(s): Hodan Issah, LGeistlinger, Folakunmi

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Mouse before antibiotic treatment

Group 1 name Corresponds to the case (exposed) group for case-control studies: Mouse after antibiotic treatment

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Mouse sample bacterial results post-antibiotic treatment using amoxicillin-acid clavulanic

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: LEfSe

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 2

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased

Signature 2

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Reviewed Marked as Reviewed by Folakunmi on 2024-1-15

Curated date: 2023/10/13

Curator: Hodan Issah

Revision editor(s): Hodan Issah, Folakunmi

Source: figure 3D

Description: Amoxicillin/clavulanate acid treatment alters the bacterial microbiota

Abundance in Group 1: increased abundance in Mouse after antibiotic treatment

NCBI	Quality Control	Links
Enterobacteriaceae
Clostridiales vadin BB60Clostridiales vadin BB60
Escherichia/Shigella sp.
Enterococcus

Revision editor(s): Hodan Issah, Folakunmi