Freschi Marco L, Künstner Axel, Huber Gianna, Stölting Ines, Busch Hauke, Hirose Misa, Raasch Walter
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.
Medical Systems Biology Group, Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
Front Pharmacol. 2024 Nov 18;15:1453989. doi: 10.3389/fphar.2024.1453989. eCollection 2024.
INTRODUCTION: Treatment of rodents with the AT 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), while controls received feces samples from vehicle/HFD-treated obese mice (BL/6>f). 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 than in BL6>f 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 than in BL/6>f mice. Moreover, the correlation between body weight and Lachnospiraceae, Desulfovibrionaceae, Desulfovibrionia uncl., or Desulfovibrio was positive in BL/6>f and negative in BL/6>f 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.
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