Lammi C, Ottaviano E, Fiore G, Bollati C, d'Adduzio L, Fanzaga M, Ceccarani C, Vizzuso S, Zuccotti G, Borghi E, Verduci E
Department of Pharmaceutical Sciences, University of Milan, 20133, Milan, Italy.
Department of Health Sciences, University of Milan, 20142, Milan, Italy.
J Endocrinol Invest. 2025 Feb;48(2):465-481. doi: 10.1007/s40618-024-02444-w. Epub 2024 Aug 26.
Docosahexaenoic acid (DHA) is a long-chain omega-3 polyunsaturated fatty acid. We investigated the dual health ability of DHA to modulate gut microbiota in children with obesity and to exert anti-inflammatory activity on human intestinal Caco-2 cells.
In a pilot study involving 18 obese children (8-14 years), participants received a daily DHA supplement (500 mg/day) and dietary intervention from baseline (T0) to 4 months (T1), followed by dietary intervention alone from 4 months (T1) to 8 months (T2). Fecal samples, anthropometry, biochemicals and dietary assessment were collected at each timepoint. At preclinical level, we evaluated DHA's antioxidant and anti-inflammatory effects on Caco-2 cells stimulated with Hydrogen peroxide (HO) and Lipopolysaccharides (LPS), by measuring also Inducible nitric oxide synthase (iNOS) levels and cytokines, respectively.
Ten children were included in final analysis. No major changes were observed for anthropometric and biochemical parameters, and participants showed a low dietary compliance at T1 and T2. DHA supplementation restored the Firmicutes/Bacteroidetes ratio that was conserved also after the DHA discontinuation at T2. DHA supplementation drove a depletion in Ruminococcaceae and Dialisteraceae, and enrichment in Bacteroidaceae, Oscillospiraceae, and Akkermansiaceae. At genus level, Allisonella was the most decreased by DHA supplementation. In Caco-2 cells, DHA decreased HO-induced reactive oxygen species (ROS) and nitric oxide (NO) production via iNOS pathway modulation. Additionally, DHA modulated proinflammatory (IL-1β, IL-6, IFN-γ, TNF-α) and anti-inflammatory (IL-10) cytokine production in LPS-stimulated Caco-2 cells.
An improvement in gut dysbiosis of children with obesity seems to be triggered by DHA and to continue after discontinuation. The ability to modulate gut microbiota, matches also with an anti-inflammatory effect of DHA on Caco-2 cells.
二十二碳六烯酸（DHA）是一种长链ω-3多不饱和脂肪酸。我们研究了DHA对肥胖儿童肠道微生物群的调节作用以及对人肠道Caco-2细胞的抗炎活性这两种健康益处。
在一项涉及18名肥胖儿童（8 - 14岁）的初步研究中，参与者从基线（T0）到4个月（T1）每天接受DHA补充剂（500毫克/天）并进行饮食干预，随后从4个月（T1）到8个月（T2）仅进行饮食干预。在每个时间点收集粪便样本、人体测量数据、生化指标和饮食评估。在临床前水平，我们通过分别测量诱导型一氧化氮合酶（iNOS）水平和细胞因子，评估了DHA对用过氧化氢（HO）和脂多糖（LPS）刺激的Caco-2细胞的抗氧化和抗炎作用。
最终分析纳入了10名儿童。人体测量和生化参数未观察到重大变化，参与者在T1和T2时饮食依从性较低。补充DHA恢复了厚壁菌门/拟杆菌门的比例，在T2停止补充DHA后该比例也得以保持。补充DHA导致瘤胃球菌科和戴阿李斯特菌科减少，拟杆菌科、颤螺菌科和阿克曼氏菌科增加。在属水平上，Allisonella受DHA补充影响下降最为明显。在Caco-2细胞中，DHA通过调节iNOS途径减少了HO诱导的活性氧（ROS）和一氧化氮（NO）生成。此外，DHA调节了LPS刺激的Caco-2细胞中促炎（IL-1β、IL-6、IFN-γ、TNF-α）和抗炎（IL-10）细胞因子的生成。
肥胖儿童肠道菌群失调的改善似乎由DHA引发，且在停药后仍持续。调节肠道微生物群的能力也与DHA对Caco-2细胞的抗炎作用相匹配。
