Oral Delivery of Ellagic Acid Encapsulated in Milk Exosomes: Sex-Based Differences in Bioavailability, Urolithin Production, and Gut Microbiota Modulation.

IF 4.5 2区农林科学 Q1 FOOD SCIENCE & TECHNOLOGY

Molecular Nutrition & Food Research Pub Date : 2025-05-12 DOI:10.1002/mnfr.70104

María Ángeles Ávila-Gálvez,María Romo-Vaquero,Carmen Mazarío-Gárgoles,Joao Tomé-Carneiro,María-Carmen López de Las Hazas,Alberto Dávalos,María Victoria Selma,Antonio González-Sarrías,Juan Carlos Espín

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引用次数: 0

Abstract

Milk exosomes (EXOs) enhance polyphenols' bioavailability, but their potential for oral administration remains underexplored. Ellagic acid (EA) is poorly bioavailable. We investigate whether EA encapsulated in EXOs (EXO-EA) consumed orally improves EA bioavailability and (or) modulates gut microbiota. For 2 weeks, BALB/c mice received EXO, non-encapsulated EA (NEA), or EXO-EA (0.27 mg EA/kg bw) orally. Targeted and untargeted metabolomics (UPLC-qTOF-MS), fecal SCFAs (GC-MS), and gut microbiota (PacBio 16S-sequencing) were performed. Additionally, EA plasma and brain kinetics were evaluated in rats following intravenous administration of EXO-EA and NEA. Unlike NEA, EXO-EA quadrupled EA plasma levels in Sprague-Dawley rats and enabled brain detection. However, oral EXO-EA in mice failed to deliver EA systemically due to gastrointestinal instability, confirmed by in vitro digestion. Sex-dependent EXO-EA metabolomic effects were observed. Also, in males only, EXO-EA increased fecal urolithin A and SCFAs and enriched the microbiota with Christensenellaceae R7, Ruminococcus species, and Clostridium fusiformis, among others. In females, both EXO-EA and NEA enriched the microbiota with bifidobacteria, including Bifidobacterium pseudolongum. Oral EXO-EA impacted plasma metabolome, modulated gut microbiota, and increased urolithin A and SCFA production sex-dependently. However, gastrointestinal instability, limited EA encapsulation, and low dose administered prevented systemic delivery.

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乳外泌体包裹的鞣花酸口服递送：生物利用度、尿素产生和肠道菌群调节的性别差异。

乳外泌体（EXOs）提高了多酚的生物利用度，但其口服给药的潜力仍未得到充分探索。鞣花酸（EA）的生物利用度很差。我们研究了口服exo （EXO-EA）胶囊中的EA是否能提高EA的生物利用度和（或）调节肠道微生物群。2周后，BALB/c小鼠口服EXO、未胶囊化EA （NEA）或EXO-EA （0.27 mg EA/kg bw）。进行靶向和非靶向代谢组学（UPLC-qTOF-MS），粪便SCFAs （GC-MS）和肠道微生物群（PacBio 16s测序）。此外，对大鼠静脉注射EXO-EA和NEA后的EA血浆和脑动力学进行了评估。与NEA不同，EXO-EA使Sprague-Dawley大鼠的EA血浆水平提高了四倍，并使大脑检测成为可能。然而，体外消化证实，口服EXO-EA小鼠由于胃肠道不稳定而无法全身递送EA。观察到性别依赖的EXO-EA代谢组效应。此外，仅在雄性中，EXO-EA增加了粪便尿素A和SCFAs，并丰富了Christensenellaceae R7、Ruminococcus和梭状芽孢杆菌等微生物群。在雌性中，EXO-EA和NEA都使双歧杆菌（包括假长双歧杆菌）的微生物群富集。口服EXO-EA影响血浆代谢组，调节肠道微生物群，增加尿素A和短链脂肪酸的产生，性别依赖性。然而，胃肠道不稳定，有限的EA包封和低剂量给药阻碍了全身给药。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Nutrition & Food Research 工程技术-食品科技

CiteScore

8.70

自引率

1.90%

发文量

250

审稿时长

1.7 months

期刊介绍： Molecular Nutrition & Food Research is a primary research journal devoted to health, safety and all aspects of molecular nutrition such as nutritional biochemistry, nutrigenomics and metabolomics aiming to link the information arising from related disciplines: Bioactivity: Nutritional and medical effects of food constituents including bioavailability and kinetics. Immunology: Understanding the interactions of food and the immune system. Microbiology: Food spoilage, food pathogens, chemical and physical approaches of fermented foods and novel microbial processes. Chemistry: Isolation and analysis of bioactive food ingredients while considering environmental aspects.