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
{"title":"Minocycline treatment attenuates high-refined carbohydrate diet-induced gut bacterial dysbiosis, anxiety-like behaviour, and cardiac damage in mice","authors":"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","doi":"10.1016/j.ejphar.2025.177552","DOIUrl":null,"url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"996 ","pages":"Article 177552"},"PeriodicalIF":4.2000,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European journal of pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014299925003061","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
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.
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.