Increase in body weight is lowered when mice received fecal microbiota transfer from donor mice treated with the AT1 receptor antagonist telmisartan
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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
Freschi ML, Künstner A, Huber G, Stölting I, Busch H, Hirose M, Raasch W
Journal
Frontiers in pharmacology
Year
2024
Keywords:
AT1 receptor antagonist, desulovibrio, microbiota transfer, obesity, renin-angiotensin aldosterone system (RAAS), telmisartan, weight reduction
INTRODUCTION: Treatment of rodents with the AT1 blocker (ARB) telmisartan (TEL) has an anti-adipose effect. Among other mechanisms, we also have attributed the anti-adipose action to diet-independent alterations in gut microbiota. Thus, we aimed here to confirm this mechanism by using the fecal microbiota transfer (FMT) approach. METHODS: Seven weeks after initiating a high-fat diet (HFD), C57BL/6N mice received fecal microbiota for 8 weeks from donor mice by oral gavage, continuing HFD feeding. Stool samples came from mice that were treated with TEL (8 mg/kg/d by gavage, 12 weeks), thus remaining lean despite HFD feeding (BL/6>fTEL), while controls received feces samples from vehicle/HFD-treated obese mice (BL/6>fVEH). Microbiota of the stool samples from these acceptor mice was analyzed by 16S rRNA gene amplicon sequencing. RESULTS: Weight gain was lower in BL6>fTEL than in BL6>fVEH mice after 3 but not 8 weeks. Energy homeostasis, insulin sensitivity, and body composition did not differ between the two groups. β-diversity indicated group differences (F = 2.27, p = 0.005). Although the Firmicutes/Bacteroides ratio did not differ, abundances of distinct phyla, families, and genera varied. Among others, Ruminococcaceae and Desulfovibrionaceae, Desulfovibrionia uncl., and Lachnospiraceae uncl. were lower in BL/6>fTEL than in BL/6>fVEH mice. Moreover, the correlation between body weight and Lachnospiraceae, Desulfovibrionaceae, Desulfovibrionia uncl., or Desulfovibrio was positive in BL/6>fVEH and negative in BL/6>fTEL mice. DISCUSSION: As FMT from TEL-pretreated mice influences the microbiota in acceptor mice with slight weight-reducing effects, we confirm the relevance of TEL-related microbiota changes for weight reduction, most likely independent of the transferred stool-residual TEL effect on the host metabolism.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-14
Subjects
- Location of subjects
- Germany
- 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
- Treatment outcome measurement Treatment outcome measurement,treatment outcome measurement
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- d0 (day 0)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- d49 (day 49)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Stool samples collected at day 49 for microbiota analysis after the mice had already been fed High Fat Diet (HFD) for 7 weeks
- Group 0 sample size Number of subjects in the control (unexposed) group
- 6
- 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-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).
- log transformation
- Statistical test
- ANCOM-BC
- 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
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-14
Source: Fig. S3B, S4B, S5B, Table S1
Description: Differential abundance analysis of phylum, family and genera between d0 and d49. At time point d0, the mice were still receiving chow diet, while d49 represents the time point immediately before FMT, when the two groups of mice had been fed HFD for 7 weeks but had not yet received microbiome transfer
Abundance in Group 1: increased abundance in d49 (day 49)
Revision editor(s): Anne-mariesharp
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-4-14
Source: Fig. S3B, S4B, S5B, Table S1
Description: Differential abundance analysis of phylum, family and genera between d0 and d49. At time point d0, the mice were still receiving chow diet, while d49 represents the time point immediately before FMT, when the two groups of mice had been fed HFD for 7 weeks but had not yet received microbiome transfer
Abundance in Group 1: decreased abundance in d49 (day 49)
Revision editor(s): Anne-mariesharp, KateRasheed
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2025-4-14
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- BL/6>fVEH
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- BL/6>fTEL
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Mice that received fecal microbiota transfer (FMT) from donor mice pre-treated with telmisartan (TEL (8mg/kg/d by gavage, 12 weeks))
- Group 0 sample size Number of subjects in the control (unexposed) group
- 12
- Group 1 sample size Number of subjects in the case (exposed) group
- 12
Lab analysis
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)
- T-Test
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-14
Source: Figure 5B, 6B, 7B
Description: Differential abundance analysis of phylum, family and genus levels between BL/6>fVEH and BL/6>fTEL
Abundance in Group 1: increased abundance in BL/6>fTEL
| NCBI | Quality Control | Links |
|---|---|---|
| Pasteurellaceae | ||
| Rodentibacter | ||
| Thomasclavelia | ||
| Alistipes_AAlistipes_A | ||
| Proteobacteria bacterium CAG:495 |
Revision editor(s): Anne-mariesharp
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-4-14
Source: Figure 5B, 6B, 7B
Description: Differential abundance analysis of phylum, family and genus levels between BL/6>fVEH and BL/6>fTEL
Abundance in Group 1: decreased abundance in BL/6>fTEL
Revision editor(s): Anne-mariesharp
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