C Lammi, E Ottaviano, G Fiore, C Bollati, L d'Adduzio, M Fanzaga, C Ceccarani, S Vizzuso, G Zuccotti, E Borghi, E Verduci
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At preclinical level, we evaluated DHA's antioxidant and anti-inflammatory effects on Caco-2 cells stimulated with Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) and Lipopolysaccharides (LPS), by measuring also Inducible nitric oxide synthase (iNOS) levels and cytokines, respectively.</p><p><strong>Results: </strong>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 H<sub>2</sub>O<sub>2</sub>-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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"465-481"},"PeriodicalIF":5.4000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785711/pdf/","citationCount":"0","resultStr":"{\"title\":\"Effect of docosahexaenoic acid as an anti-inflammatory for Caco-2 cells and modulating agent for gut microbiota in children with obesity (the DAMOCLE study).\",\"authors\":\"C Lammi, E Ottaviano, G Fiore, C Bollati, L d'Adduzio, M Fanzaga, C Ceccarani, S Vizzuso, G Zuccotti, E Borghi, E Verduci\",\"doi\":\"10.1007/s40618-024-02444-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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 (H<sub>2</sub>O<sub>2</sub>) and Lipopolysaccharides (LPS), by measuring also Inducible nitric oxide synthase (iNOS) levels and cytokines, respectively.</p><p><strong>Results: </strong>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 H<sub>2</sub>O<sub>2</sub>-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.</p><p><strong>Conclusion: </strong>An improvement in gut dysbiosis of children with obesity seems to be triggered by DHA and to continue after discontinuation. 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引用次数: 0
摘要
目的：二十二碳六烯酸（DHA）是一种长链欧米加-3 多不饱和脂肪酸。我们研究了 DHA 调节肥胖儿童肠道微生物群和对人体肠道 Caco-2 细胞发挥抗炎活性的双重健康能力：在一项涉及18名肥胖儿童（8-14岁）的试验性研究中，参与者从基线（T0）到4个月（T1）期间每天接受DHA补充剂（500毫克/天）和饮食干预，然后从4个月（T1）到8个月（T2）期间只接受饮食干预。在每个时间点收集粪便样本、人体测量、生化指标和饮食评估。在临床前阶段，我们分别通过测量诱导型一氧化氮合酶（iNOS）水平和细胞因子，评估了 DHA 在过氧化氢（H2O2）和脂多糖（LPS）刺激下对 Caco-2 细胞的抗氧化和抗炎作用：最终分析包括 10 名儿童。人体测量和生化参数没有发生重大变化，参与者在 T1 和 T2 期的饮食依从性较低。补充 DHA 恢复了固醇菌/类杆菌的比例，在 T2 阶段停止补充 DHA 后，这一比例也保持不变。补充 DHA 后，反刍球菌科（Ruminococcaceae）和 Dialisteraceae 的数量减少，而类菌科（Bacteroidaceae）、弧菌科（Oscillospiraceae）和 Akkermansiaceae 的数量增加。在属的水平上，Allisonella 因补充 DHA 而减少最多。在 Caco-2 细胞中，DHA 通过调节 iNOS 途径减少了 H2O2 诱导的活性氧（ROS）和一氧化氮（NO）的产生。此外，DHA 还能调节 LPS 刺激的 Caco-2 细胞中的促炎细胞因子（IL-1β、IL-6、IFN-γ、TNF-α）和抗炎细胞因子（IL-10）的产生：结论：肥胖症儿童肠道菌群失调的改善似乎是由 DHA 引起的，并且在停药后仍会持续。DHA 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。
Effect of docosahexaenoic acid as an anti-inflammatory for Caco-2 cells and modulating agent for gut microbiota in children with obesity (the DAMOCLE study).
Purpose: 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.
Methods: 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 (H2O2) and Lipopolysaccharides (LPS), by measuring also Inducible nitric oxide synthase (iNOS) levels and cytokines, respectively.
Results: 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 H2O2-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.
Conclusion: 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.
期刊介绍：
The Journal of Endocrinological Investigation is a well-established, e-only endocrine journal founded 36 years ago in 1978. It is the official journal of the Italian Society of Endocrinology (SIE), established in 1964. Other Italian societies in the endocrinology and metabolism field are affiliated to the journal: Italian Society of Andrology and Sexual Medicine, Italian Society of Obesity, Italian Society of Pediatric Endocrinology and Diabetology, Clinical Endocrinologists’ Association, Thyroid Association, Endocrine Surgical Units Association, Italian Society of Pharmacology.
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