Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca 62210, Morelos, Mexico.
Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca 62210, Morelos, Mexico.
Int J Mol Sci. 2024 Jun 24;25(13):6904. doi: 10.3390/ijms25136904.
Obesity is a global health concern implicated in numerous chronic degenerative diseases, including type 2 diabetes, dyslipidemia, and neurodegenerative disorders. It is characterized by chronic low-grade inflammation, gut microbiota dysbiosis, insulin resistance, glucose intolerance, and lipid metabolism disturbances. Here, we investigated the therapeutic potential of environmental enrichment (EE) to prevent the progression of gut dysbiosis in mice with high-fat diet (HFD)-induced metabolic syndrome. C57BL/6 male mice with obesity and metabolic syndrome, continuously fed with an HFD, were exposed to EE. We analyzed the gut microbiota of the mice by sequencing the 16s rRNA gene at different intervals, including on day 0 and 12 and 24 weeks after EE exposure. Fasting glucose levels, glucose tolerance, insulin resistance, food intake, weight gain, lipid profile, hepatic steatosis, and inflammatory mediators were evaluated in serum, adipose tissue, and the colon. We demonstrate that EE intervention prevents the progression of HFD-induced dysbiosis, reducing taxa associated with metabolic syndrome (, , and ) while promoting those linked to healthy physiology (, , , and ). Furthermore, EE enhances intestinal barrier integrity, increases mucin-producing goblet cell population, and upregulates Muc2 expression in the colon. These alterations correlate with reduced systemic lipopolysaccharide levels and attenuated colon inflammation, resulting in normalized glucose metabolism, diminished adipose tissue inflammation, reduced liver steatosis, improved lipid profiles, and a significant reduction in body weight gain despite mice's continued HFD consumption. Our findings highlight EE as a promising anti-inflammatory strategy for managing obesity-related metabolic dysregulation and suggest its potential in developing probiotics targeting EE-modulated microbial taxa.
肥胖是一个全球性的健康问题，与许多慢性退行性疾病有关，包括 2 型糖尿病、血脂异常和神经退行性疾病。它的特征是慢性低度炎症、肠道微生物失调、胰岛素抵抗、葡萄糖耐量受损和脂质代谢紊乱。在这里，我们研究了环境富集（EE）预防高脂肪饮食（HFD）诱导的代谢综合征小鼠肠道失调进展的治疗潜力。连续喂食 HFD 的肥胖和代谢综合征 C57BL/6 雄性小鼠暴露于 EE 中。我们通过在不同时间点（包括 EE 暴露后 0 天、12 天和 24 周）对 16s rRNA 基因进行测序来分析小鼠的肠道微生物群。评估血清、脂肪组织和结肠中的空腹血糖水平、葡萄糖耐量、胰岛素抵抗、食物摄入量、体重增加、血脂谱、肝脂肪变性和炎症介质。我们证明 EE 干预可预防 HFD 诱导的失调进展，减少与代谢综合征相关的分类群（，，和），同时促进与健康生理学相关的分类群（，，，和）。此外，EE 增强了肠道屏障完整性，增加了产生粘蛋白的杯状细胞数量，并在上皮细胞中上调了 Muc2 的表达。这些变化与系统内脂多糖水平降低和结肠炎症减轻相关，导致葡萄糖代谢正常化、脂肪组织炎症减少、肝脂肪变性改善、血脂谱改善以及尽管小鼠继续食用 HFD 但体重增加显著减少。我们的研究结果强调了 EE 作为一种治疗肥胖相关代谢失调的有前途的抗炎策略，并表明其在开发针对 EE 调节的微生物分类群的益生菌方面具有潜力。
