Kidney Week

Abstract: TH-PO192

Modulation of Blood Pressure through Microbiome Exchange between Milan Normotensive and Hypertensive Rat Strains

Session Information

• Hypertension and CVD: Basic Research Findings
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1601 Hypertension and CVD: Basic

Authors

• Capasso, Giovambattista, Biogem, Biology and Molecular Genetics Institute, Ariano Irpino, Italy

Giovambattista Capasso, MD, PhD

• Suzumoto, Yoko, Biogem, Biology and Molecular Genetics Institute, Ariano Irpino, Italy

Yoko Suzumoto

• Silvestri, Cristoforo, CRIUCPQ, INAF and Centre NUTRISS, Université Laval, Québec, Quebec, Canada

Cristoforo Silvestri

• Shams, Abbas, Biogem, Biology and Molecular Genetics Institute, Ariano Irpino, Italy

Abbas Shams

• D'Apolito, Luciano, Biogem, Biology and Molecular Genetics Institute, Ariano Irpino, Italy

Luciano D'Apolito, PhD

• Villanova, Antonio, Biogem, Biology and Molecular Genetics Institute, Ariano Irpino, Italy

Antonio Villanova

• Trepiccione, Francesco, University of Campania 'L. Vanvitelli', Naples, Italy

Francesco Trepiccione, MD, PhD

• Di Marzo, Vincenzo, CRIUCPQ, INAF and Centre NUTRISS, Université Laval, Québec, Quebec, Canada

Vincenzo Di Marzo, PhD

Background

Hypertension constitutes a major health problem leading to cardiovascular diseases. A number of studies showed gut microbiome changes in hypertension, suggesting kidney-gut axis in hypertension. A congenic strain of Milan hypertensive (NA) rats with a mutation in α-adducin gene develops hypertension at 3 months age. Our preliminary study revealed diverse expression of renal sodium transporters in NA rats compared with normotensive strain (MN) rats, indicating abnormal renal salt handling in NA rats. Present study aimed at investigating a possible connection between gut microbiome and blood pressure phenotype in these two strains. We evaluated whether exchange of faeces between two strains may transfer phenotypes via gut microbiome, and mechanisms underlying altered phenotypes were investigated.

Methods

NA and MN rats were subjected to ‘homogenization (HOM)’ of the microbiome, consisted of exchanges of bedding with faeces, followed by co-housing in the same cage (MN-HOM and NA-HOM groups). For the baseline (BSL) condition, rats were homogenized within the same strain (MN-BSL and NA-BSL). Systolic blood pressure (SBP) was measured every month. Faeces were collected for microbiota metataxonomic analysis using next generation sequencing of 16S ribosome encoding DNA.

Results

At 5 month, SBP in MN-BSL was averaged at 143.6 mmHg, while SBP of NA-BSL was 163.3 mmHg, confirming the hypertensive phenotype in NA rats at baseline. MN-HOM showed a significantly enhanced SBP compared to MN-BSL, reaching 153.5 mmHg. The average SBP of NA-HOM was163.7 mmHg, indicating that homogenization did not have impact on SBP in NA rats. The SBP of MN-HOM was still significantly lower than both the NA-BSL and NA-HOM groups. Different gut microbiota compositions were observed in the two strains of rats at baseline, and HOM altered both.

Conclusion

We have demonstrated that the hypertensive phenotype in NA rats was transferred to MN rats through homogenization, indicating that the intestinal microbiota or metabolites derived therefrom could eventually modulate SBP. Further studies are required to unveil the molecular mechanisms by which the gut microbiome modulates blood pressure.