Investigation of the relationship between inflammation and microbiota in the intestinal tissue of female and male rats fed with fructose: Modulatory role of metformin.

IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY
DARU Journal of Pharmaceutical Sciences Pub Date : 2024-12-01 Epub Date: 2024-06-17 DOI:10.1007/s40199-024-00521-2
Azimet Yalçın Buğdaycı, Saadet Özen Akarca Dizakar, Mürşide Ayşe Demirel, Suna Ömeroğlu, Fatma Akar, Mecit Orhan Uludağ
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Abstract

Background: It has been reported that High-Fructose (HF) consumption, considered one of the etiological factors of Metabolic Syndrome (MetS), causes changes in the gut microbiota and metabolic disorders. There is limited knowledge on the effects of metformin in HF-induced intestinal irregularities in male and female rats with MetS.

Objectives: In this study, we investigated the sex-dependent effects of metformin treatment on the gut microbiota, intestinal Tight Junction (TJ) proteins, and inflammation parameters in HF-induced MetS.

Methods: Fructose was given to the male and female rats as a 20% solution in drinking water for 15 weeks. Metformin (200 mg/kg) was administered by gastric tube once a day during the final seven weeks. Biochemical, histopathological, immunohistochemical, and bioinformatics analyses were performed. Differences were considered statistically significant at p < 0.05.

Results: The metformin treatment in fructose-fed rats promoted glucose, insulin, Homeostasis Model Assessment of Insulin Resistance Index (HOMA-IR), and Triglyceride (TG) values in both sexes. The inflammation score was significantly decreased with metformin treatment in fructose-fed male and female rats (p < 0.05). Moreover, metformin treatment significantly decreased Interleukin-1 Beta (IL-1β) and Tumor Necrosis Factor-Alpha (TNF-α) in ileum tissue from fructose-fed males (p < 0.05). Intestinal immunoreactivity of Occludin and Claudin-1 was increased with metformin treatment in fructose-fed female rats. HF and metformin treatment changed the gut microbial composition. Firmicutes/Bacteroidetes (F/B) ratio increased with HF in females. In the disease group, Bifidobacterium pseudolongum; in the treatment group, Lactobacillus helveticus and Lactobacillus reuteri are the prominent species in both sexes. When the male and female groups were compared, Akkermansia muciniphila was prominent in the male treatment group.

Conclusion: In conclusion, metformin treatment promoted biochemical parameters in both sexes of fructose-fed rats. Metformin showed a sex-dependent effect on inflammation parameters, permeability factors, and gut microbiota. Metformin has partly modulatory effects on fructose-induced intestinal changes.

Abstract Image

研究果糖喂养的雌性和雄性大鼠肠道组织中炎症与微生物群之间的关系:二甲双胍的调节作用
背景:据报道,摄入高果糖(HF)被认为是代谢综合征(MetS)的病因之一,会导致肠道微生物群的变化和代谢紊乱。关于二甲双胍对 HF 诱导的代谢综合征雌雄大鼠肠道功能紊乱的影响,目前所知有限:本研究探讨了二甲双胍治疗对高频诱导 MetS 大鼠肠道微生物群、肠道 TJ 蛋白和炎症参数的性别依赖性影响:方法:将 20% 的果糖溶于饮用水中,给雌雄大鼠服用 15 周。在最后七周,每天一次通过胃管给药二甲双胍(200 毫克/千克)。对大鼠进行了生化、组织病理学、免疫组化和生物信息学分析。结果显示,二甲双胍治疗果蝇的结果与二甲双胍治疗果蝇的结果有显著统计学差异:二甲双胍治疗果糖喂养大鼠可提高雌雄大鼠的血糖、胰岛素、胰岛素抵抗指数稳态模型评估(HOMA-IR)和甘油三酯(TG)值。二甲双胍治疗后,果糖喂养的雄性和雌性大鼠的炎症评分均明显降低(p 结论:二甲双胍治疗对大鼠的炎症评分有促进作用:总之,二甲双胍治疗对果糖喂养大鼠的生化指标均有促进作用。二甲双胍对炎症参数、渗透因子和肠道微生物群的影响与性别有关。二甲双胍对果糖引起的肠道变化具有部分调节作用。
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来源期刊
DARU Journal of Pharmaceutical Sciences
DARU Journal of Pharmaceutical Sciences PHARMACOLOGY & PHARMACY-
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期刊介绍: DARU Journal of Pharmaceutical Sciences is a peer-reviewed journal published on behalf of Tehran University of Medical Sciences. The journal encompasses all fields of the pharmaceutical sciences and presents timely research on all areas of drug conception, design, manufacture, classification and assessment. The term DARU is derived from the Persian name meaning drug or medicine. This journal is a unique platform to improve the knowledge of researchers and scientists by publishing novel articles including basic and clinical investigations from members of the global scientific community in the forms of original articles, systematic or narrative reviews, meta-analyses, letters, and short communications.
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