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. 2025 Jun 5:996:177552.
doi: 10.1016/j.ejphar.2025.177552. Epub 2025 Mar 26.

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

Alessandra Oliveira Silva  1 , Jéssyca Milene Ribeiro  1 , Nícia Pedreira Soares  2 , Karla Caroline Marques Oliveira  2 , Patrícia Ferreira Espuri  3 , Thiago Caetano Andrade Belo  4 , Luis Felipe Cunha Dos Reis  5 , Daniele Cristina de Aguiar  2 , Fernanda Borges de Araújo Paula  6 , Sílvia Graciela Ruginsk  7 , Leonardo Augusto de Almeida  4 , Marcos José Marques  3 , Antunes-Rodrigues José  8 , Lucila Leico Kagohara Elias  8 , Larissa Helena Lobo Torres  1 , Stefany Cau  2 , Carla Speroni Ceron  9
Affiliations

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

Alessandra Oliveira Silva et al. Eur J Pharmacol. .

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.

Keywords: Anxiety; Cardiovascular disease; Gastrointestinal microbiome; High-refined carbohydrate diet; Minocycline; Oxidative stress.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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