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

Dietary influences on the Dahl SS rat gut microbiota and its effects on salt-sensitive hypertension and renal damage.
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DOI:
10.1111/apha.13662
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发表时间:
2021-08
期刊:
影响因子:
6.3
通讯作者:
Mattson, David L.
Mattson, David L.
中科院分区:
医学1区
文献类型:
--
作者:
Abais-Battad, Justine M.;Saravia, Fatima L.;Lund, Hayley;Dasinger, John Henry;Fehrenbach, Daniel J.;Alsheikh, Ammar J.;Zemaj, Jeylan;Kirby, John R.;Mattson, David L.

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我们以前的研究已经证明了饮食因素在测定Dahl盐敏感(SS)大鼠高血压中的重要性。由于肠道微生物群与高血压等慢性疾病有关,我们假设饮食改变会改变微生物群,从而介导盐敏感性高血压和肾脏疾病的发展。本研究使用来自威斯康星州医学院(SS/MCW)的SS大鼠,其维持在纯化的基于酪蛋白的饮食(0.4% NaCl AIN-76 A,染料)上,以及来自Charles River实验室(SS/CRL)的大鼠,其饲喂全谷物饮食(0.75% NaCl 5L 79,LabDiet)。使用粪便16 S rDNA测序来表型肠道微生物群。直接检查肠道微生物群的贡献,对SS/CRL大鼠施用SS/MCW粪便或媒介物(Vehl)与HS AIN-76 A饮食结合的粪便微生物群转移(FMT)实验。当喂食高盐(HS,4.0%NaCl AIN-76 A)时,SS/MCW大鼠表现出肾损伤和炎症,这在SS/CRL中显著减弱。肠道微生物群表型分析揭示了与疾病严重程度相关的不同特征。SS/MCW FMT使SS/CRL对HS的反应恶化,表现为白蛋白尿增加(67.4 ± 6.9 vs 113.7 ± 25.0 mg/d,Vehl vs FMT,P = 0.007)、动脉收缩压增加(158.6 ± 5.8 vs 177.8 ± 8.9 mmHg,Vehl vs FMT,P = 0.09)和肾T细胞浸润(1.9倍)。基于扩增子序列变体(ASV)的粪便16 S rDNA测序数据分析显示,FMT显著改变了分类群:丹毒丝菌科_2、戈登副杆菌、解乳链球菌、拟杆菌科_1、脱硫弧菌科_2、白色瘤胃球菌。这些数据表明,肠道微生物群的饮食调节直接有助于Dahl SS高血压和肾损伤的发展。
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. 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. 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. These data demonstrate that dietary modulation of the gut microbiota directly contributes to the development of Dahl SS hypertension and renal injury.
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