Gut dysbiosis induced by cardiac pressure overload enhances adverse cardiac remodeling in a T cell-dependent manner.
Gut dysbiosis induced by cardiac pressure overload enhances adverse cardiac remodeling in a T cell-dependent manner.
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DOI：
10.1080/19490976.2020.1823801
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发表时间：
2020-11-09
期刊：
影响因子：
12.2
通讯作者：
Alcaide P
中科院分区：
文献类型：
--
作者：
Carrillo-Salinas FJ;Anastasiou M;Ngwenyama N;Kaur K;Tai A;Smolgovsky SA;Jetton D;Aronovitz M;Alcaide P
尽管存在心力衰竭（HF）中肠道生态失调和T细胞炎症的相关性，但肠道微生物是否以及如何促进HF中的T细胞免疫应答、心脏纤维化和功能障碍仍在很大程度上未被探索。我们的目的是研究肠道生态失调是否由心脏压力超负荷引起，以及其在T细胞活化、不良心脏重塑和心功能障碍中的作用。我们使用粪便样本的16 S rRNA测序，发现由横向主动脉缩窄（TAC）诱导的心脏压力超负荷导致肠道生态失调，其特征是WT小鼠中色氨酸和短链脂肪酸产生细菌的减少，但在T细胞缺陷小鼠（Tcra−/-）小鼠中则不然。这些变化不会导致肠道中的T细胞活化或肠道屏障破坏。引人注目的是，WT小鼠中的微生物群耗竭导致心脏T细胞浸润减少，心脏纤维化减少，并响应于TAC而保护心脏免受收缩功能障碍。微生物群的自发重建部分逆转了这些影响。我们观察到野生型小鼠心脏中芳烃受体（AhR）和与色氨酸代谢相关的酶的表达降低，但在Tcra−/-小鼠或微生物群耗尽的小鼠中没有。这些研究结果表明，心脏压力超负荷诱导的肠道生态失调和T细胞免疫反应有助于不良心脏重塑，并确定色氨酸代谢物和AhR对保护HF患者免受不良心脏重塑和收缩功能障碍的潜在贡献。
Despite the existing association of gut dysbiosis and T cell inflammation in heart failure (HF), whether and how gut microbes contribute to T cell immune responses, cardiac fibrosis and dysfunction in HF remains largely unexplored. Our objective was to investigate whether gut dysbiosis is induced by cardiac pressure overload, and its effect in T cell activation, adverse cardiac remodeling, and cardiac dysfunction. We used 16S rRNA sequencing of fecal samples and discovered that cardiac pressure overload-induced by transverse aortic constriction (TAC) results in gut dysbiosis, characterized by a reduction of tryptophan and short-chain fatty acids producing bacteria in WT mice, but not in T cell-deficient mice (Tcra−/-) mice. These changes did not result in T cell activation in the gut or gut barrier disruption. Strikingly, microbiota depletion in WT mice resulted in decreased heart T cell infiltration, decreased cardiac fibrosis, and protection from systolic dysfunction in response to TAC. Spontaneous reconstitution of the microbiota partially reversed these effects. We observed decreased cardiac expression of the Aryl hydrocarbon receptor (AhR) and enzymes associated with tryptophan metabolism in WT mice, but not in Tcra−/- mice, or in mice depleted of the microbiota. These findings demonstrate that cardiac pressure overload induced gut dysbiosis and T cell immune responses contribute to adverse cardiac remodeling, and identify the potential contribution of tryptophan metabolites and the AhR to protection from adverse cardiac remodeling and systolic dysfunction in HF.
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影响因子：
4.6
作者：
Natarajan, Niranjana;Hori, Daijiro;Pluznick, Jennifer L.
通讯作者：
Pluznick, Jennifer L.
DOI：
10.1161/circheartfailure.115.002225
发表时间：
2015-07
期刊：
Circulation. Heart failure
影响因子：
--
作者：
Nevers T;Salvador AM;Grodecki-Pena A;Knapp A;Velázquez F;Aronovitz M;Kapur NK;Karas RH;Blanton RM;Alcaide P
通讯作者：
Alcaide P
DOI：
10.1073/pnas.1019378108
发表时间：
2011-03-29
影响因子：
11.1
作者：
Ichinohe, Takeshi;Pang, Iris K.;Iwasaki, Akiko
通讯作者：
Iwasaki, Akiko
影响因子：
3.7
作者：
Kamo T;Akazawa H;Suda W;Saga-Kamo A;Shimizu Y;Yagi H;Liu Q;Nomura S;Naito AT;Takeda N;Harada M;Toko H;Kumagai H;Ikeda Y;Takimoto E;Suzuki JI;Honda K;Morita H;Hattori M;Komuro I
通讯作者：
Komuro I
影响因子：
15.9
作者：
Chintalgattu, Vishnu;Ai, Di;Khakoo, Aarif Y.
通讯作者：
Khakoo, Aarif Y.