Increase in body weight is lowered when mice received fecal microbiota transfer from donor mice treated with the AT1 receptor antagonist telmisartan

Marco L Freschi; Axel Künstner; Gianna Huber; Ines Stölting; Hauke Busch; Misa Hirose; Walter Raasch

doi:10.3389/fphar.2024.1453989

Increase in body weight is lowered when mice received fecal microbiota transfer from donor mice treated with the AT₁ receptor antagonist telmisartan

Front Pharmacol. 2024 Nov 18:15:1453989. doi: 10.3389/fphar.2024.1453989. eCollection 2024.

Authors

Marco L Freschi¹, Axel Künstner², Gianna Huber^{1

3

4}, Ines Stölting¹, Hauke Busch², Misa Hirose⁵, Walter Raasch^{1

3

4}

Affiliations

¹ Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.
² Medical Systems Biology Group, Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
³ DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany.
⁴ CBBM (Center of Brain, Behavior and Metabolism), Lübeck, Germany.
⁵ Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.

Abstract

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>f^TEL), while controls received feces samples from vehicle/HFD-treated obese mice (BL/6>f^VEH). Microbiota of the stool samples from these acceptor mice was analyzed by 16S rRNA gene amplicon sequencing.

Results: Weight gain was lower in BL6>f^TEL than in BL6>f^VEH 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>f^TEL than in BL/6>f^VEH mice. Moreover, the correlation between body weight and Lachnospiraceae, Desulfovibrionaceae, Desulfovibrionia uncl., or Desulfovibrio was positive in BL/6>f^VEH and negative in BL/6>f^TEL 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.

Keywords: AT1 receptor antagonist; desulovibrio; microbiota transfer; obesity; renin-angiotensin aldosterone system (RAAS); telmisartan; weight reduction.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by research grants from the German Research Foundation to the GRK 1957 “Adipocyte-Brain Crosstalk,” University of Lübeck.