Dataset Information

Dietary influences on the Dahl SS rat gut microbiota and its effects on salt-sensitive hypertension and renal damage.

ABSTRACT:

Aim

Our previous studies have demonstrated the importance of dietary factors in the determination of hypertension in Dahl salt-sensitive (SS) rats. Since the gut microbiota has been implicated in chronic diseases like hypertension, we hypothesized that dietary alterations shift the microbiota to mediate the development of salt-sensitive hypertension and renal disease.

Methods

This study utilized SS rats from the Medical College of Wisconsin (SS/MCW) maintained on a purified, casein-based diet (0.4% NaCl AIN-76A, Dyets) and from Charles River Laboratories (SS/CRL) fed a whole grain diet (0.75% NaCl 5L79, LabDiet). Faecal 16S rDNA sequencing was used to phenotype the gut microbiota. Directly examining the contribution of the gut microbiota, SS/CRL rats were administered faecal microbiota transfer (FMT) experiments with either SS/MCW stool or vehicle (Vehl) in conjunction with the HS AIN-76A diet.

Results

SS/MCW rats exhibit renal damage and inflammation when fed high salt (HS, 4.0% NaCl AIN-76A), which is significantly attenuated in SS/CRL. Gut microbiota phenotyping revealed distinct profiles that correlate with disease severity. SS/MCW FMT worsened the SS/CRL response to HS, evidenced by increased albuminuria (67.4 ± 6.9 vs 113.7 ± 25.0 mg/day, Vehl vs FMT, P = .007), systolic arterial pressure (158.6 ± 5.8 vs 177.8 ± 8.9 mmHg, Vehl vs FMT, P = .09) and renal T-cell infiltration (1.9-fold). Amplicon sequence variant (ASV)-based analysis of faecal 16S rDNA sequencing data revealed taxa that significantly shifted with FMT: Erysipelotrichaceae_2, Parabacteroides gordonii, Streptococcus alactolyticus, Bacteroidales_1, Desulfovibrionaceae_2, Ruminococcus albus.

Conclusions

These data demonstrate that dietary modulation of the gut microbiota directly contributes to the development of Dahl SS hypertension and renal injury.

SUBMITTER: Abais-Battad JM

PROVIDER: S-EPMC9835005 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

Dietary influences on the Dahl SS rat gut microbiota and its effects on salt-sensitive hypertension and renal damage.

Abais-Battad Justine M JM Saravia Fatima L FL Lund Hayley H Dasinger John Henry JH Fehrenbach Daniel J DJ Alsheikh Ammar J AJ Zemaj Jeylan J Kirby John R JR Mattson David L DL

Acta physiologica (Oxford, England) 20210426 4

<h4>Aim</h4>Our previous studies have demonstrated the importance of dietary factors in the determination of hypertension in Dahl salt-sensitive (SS) rats. Since the gut microbiota has been implicated in chronic diseases like hypertension, we hypothesized that dietary alterations shift the microbiota to mediate the development of salt-sensitive hypertension and renal disease.<h4>Methods</h4>This study utilized SS rats from the Medical College of Wisconsin (SS/MCW) maintained on a purified, casei ...[more]

PMID: 33866692

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Project description:BackgroundGuizhi decoction (GZD), a classical Chinese herbal formula, has been widely used to treat hypertension, but its underlying mechanisms remain elusive. The present study aimed to explore the potential mechanisms and therapeutic effects of GZD on hypertension by integrating network pharmacology and experimental validation.MethodsThe active ingredients and corresponding targets were collected from the Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP). The targets related to hypertension were identified from the CTD, GeneCards, OMIM and Drugbank databases. Multiple networks were constructed to identify the key compounds, hub targets, and main biological processes and pathways of GZD against hypertension. The Surflex-Dock software was used to validate the binding affinity between key targets and their corresponding active compounds. The Dahl salt-sensitive rat model was used to evaluate the therapeutic effects of GZD against hypertension.ResultsA total of 112 active ingredients, 222 targets of GZD and 341 hypertension-related targets were obtained. Furthermore, 56 overlapping targets were identified, five of which were determined as the hub targets for experimental verification, including interleukin 6 (IL-6), C-C motif chemokine 2 (CCL2), IL-1β, matrix metalloproteinase 2 (MMP-2), and MMP-9. Pathway enrichment analysis results indicated that 56 overlapping targets were mainly enriched in several inflammation pathways such as the tumor necrosis factor (TNF) signaling pathway, Toll-like receptor (TLR) signaling pathway and nuclear factor kappa-B (NF-κB) signaling pathway. Molecular docking confirmed that most active compounds of GZD could bind tightly to the key targets. Experimental studies revealed that the administration of GZD improved blood pressure, reduced the area of cardiac fibrosis, and inhibited the expression of IL-6, CCL2, IL-1β, MMP-2 and MMP-9 in rats.ConclusionThe potential mechanisms and therapeutic effects of GZD on hypertension may be attributed to the regulation of cardiac inflammation and fibrosis.

Dataset Information

Dietary influences on the Dahl SS rat gut microbiota and its effects on salt-sensitive hypertension and renal damage.

Aim

Methods

Results

Conclusions

Publications

Dietary influences on the Dahl SS rat gut microbiota and its effects on salt-sensitive hypertension and renal damage.

Similar Datasets

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