Minocycline treatment attenuates high-refined carbohydrate diet-induced gut bacterial dysbiosis, anxiety-like behaviour, and cardiac damage in mice

IF 4.2 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Alessandra Oliveira Silva , Jéssyca Milene Ribeiro , Nícia Pedreira Soares , Karla Caroline Marques Oliveira , Patrícia Ferreira Espuri , Thiago Caetano Andrade Belo , Luis Felipe Cunha dos Reis , Daniele Cristina de Aguiar , Fernanda Borges de Araújo Paula , Sílvia Graciela Ruginsk , Leonardo Augusto de Almeida , Marcos José Marques , Antunes-Rodrigues José , Lucila Leico Kagohara Elias , Larissa Helena Lobo Torres , Stefany Cau , Carla Speroni Ceron
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Abstract

The high-refined carbohydrate diet (HC diet) is linked to anxiety development and oxidative damage to heart tissue. However, little is known about how the gut microbiota profile is modulated in this diet model. Minocycline is an antibiotic with anti-inflammatory, antioxidant, and matrix metalloproteinases (MMPs) inhibitor properties. Therefore, we evaluated the effects of minocycline treatment on HC diet-induced cardiac damage, anxiety-like behaviour, and bacterial gut dysbiosis in mice. Male BALB/C mice were divided into two groups, which received standard diet or HC diet for 12 weeks. In the 10th week, both groups were subdivided and received water or minocycline (50 mg/kg) by gavage for 15 days. The gut bacterial populations, behavioural parameters, adiposity index, biochemical profile, cardiac oxidative stress indicators, MMPs, cardiac remodelling, and contractile analyses by Langendorff-perfused hearts were analysed. The HC diet induced bacterial gut dysbiosis and anxiety-like behaviour increased the adiposity index with changes in the lipid profile and creatine kinase fraction MB (CK-MB). In the heart, the HC diet increased tissue oxidative stress, MMP-2 and MMP-9 activity, collagen deposition, and altered cardiac performance. Minocycline treatment reversed diet-induced bacterial gut dysbiosis and anxiety-like behaviour, ameliorated the biochemical profile, diminished oxidative stress, MMP activity, cardiac collagen deposition, and improved cardiac performance. These findings suggest that minocycline treatment modulated the microbiota and attenuated behavioural changes and cardiac damage caused by the HC diet, suggesting an interplay between the gut-microbiota-brain axis and cardiac damage caused by the HC diet consumption.

Abstract Image

二甲胺四环素治疗可减轻高精制碳水化合物饮食引起的肠道细菌生态失调、焦虑样行为和小鼠心脏损伤
高精制碳水化合物饮食(HC饮食)与焦虑的发展和心脏组织的氧化损伤有关。然而,人们对这种饮食模式如何调节肠道微生物群知之甚少。米诺环素是一种具有抗炎、抗氧化和基质金属蛋白酶(MMPs)抑制剂特性的抗生素。因此,我们评估了二甲胺四环素治疗对HC饮食诱导的小鼠心脏损伤、焦虑样行为和细菌肠道生态失调的影响。雄性BALB/C小鼠分为两组,分别饲喂标准日粮和HC日粮,为期12周。第10周,两组再分组,给予水或米诺环素(50 mg/kg)灌胃,持续15 d。对langendorff灌注心脏的肠道细菌数量、行为参数、肥胖指数、生化特征、心脏氧化应激指标、MMPs、心脏重构和收缩分析进行了分析。HC饮食诱导的细菌肠道失调和焦虑样行为增加了肥胖指数,并改变了脂质谱和肌酸激酶分数MB (CK-MB)。在心脏中,HC饮食增加了组织氧化应激、MMP-2和MMP-9活性、胶原沉积,并改变了心脏功能。米诺环素治疗逆转了饮食诱导的细菌肠道失调和焦虑样行为,改善了生化特征,减少了氧化应激、MMP活性、心脏胶原沉积,并改善了心脏功能。这些发现表明,二甲胺四环素治疗调节了微生物群,减轻了HC饮食引起的行为变化和心脏损伤,表明肠道-微生物群-脑轴与HC饮食引起的心脏损伤之间存在相互作用。
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来源期刊
CiteScore
9.00
自引率
0.00%
发文量
572
审稿时长
34 days
期刊介绍: The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems. The scope includes: Behavioural pharmacology Neuropharmacology and analgesia Cardiovascular pharmacology Pulmonary, gastrointestinal and urogenital pharmacology Endocrine pharmacology Immunopharmacology and inflammation Molecular and cellular pharmacology Regenerative pharmacology Biologicals and biotherapeutics Translational pharmacology Nutriceutical pharmacology.
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