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生物活性鱼胶原蛋白肽通过甘露糖受体激活使结肠巨噬细胞表型定向化,从而减弱肠道炎症。

Bioactive fish collagen peptides weaken intestinal inflammation by orienting colonic macrophages phenotype through mannose receptor activation.

机构信息

UMR 152 Pharma Dev, Université de Toulouse, IRD, UPS, Toulouse, France.

RESTORE Research Center, Université de Toulouse, INSERM, CNRS, EFS, ENVT, Université P. Sabatier, Toulouse, France.

出版信息

Eur J Nutr. 2022 Jun;61(4):2051-2066. doi: 10.1007/s00394-021-02787-7. Epub 2022 Jan 8.

Abstract

PURPOSE

Particular interest is now given to the potential of dietary supplements as alternative non-pharmacological approaches in intestinal inflammation handling. In this aim, this study evaluates the efficiency of fish collagen peptides, NaticolGut, on colonic inflammation.

METHODS

Wild type and Mannose receptor-deficient in the myeloid lineage C57BL/6 mice were administered with Dextran Sodium Sulfate (DSS), NaticolGut, DSS, and NaticolGut or only water for 4 or 8 days. Inflammatory status was evaluated by establishing macroscopic and microscopic scores, by measuring cytokine and calprotectin production by ELISA and the myeloperoxidase activity by chemiluminescence. Colonic macrophages were phenotyped by measuring mRNA levels of specific markers of inflammation and oxidative status. Colonic immune populations and T-cell activation profiles were determined by flow cytometry. Mucosa-associated gut microbiota assessment was undertaken by qPCR. The phenotype of human blood monocytes from inflammatory bowel disease (IBD) subjects was characterized by RT-qPCR and flow cytometry and their oxidative activity by chemiluminescence.

RESULTS

NaticolGut-treated DSS mice showed attenuated colonic inflammation compared to mice that were only exposed to DSS. NaticolGut activity was displayed through its ability to orient the polarization of colonic macrophage towards an anti-inflammatory and anti-oxidant phenotype after its recognition by the mannose receptor. Subsequently, NaticolGut delivery modulated CD4 T cells in favor of a Th2 response and dampened CD8 T-cell activation. This immunomodulation resulted in an intestinal eubiosis. In human monocytes from IBD subjects, the treatment with NaticolGut also restored an anti-inflammatory and anti-oxidant phenotype.

CONCLUSION

NaticolGut acts as a protective agent against colitis appearing as a new functional food and an innovative and complementary approach in gut health.

摘要

目的

人们现在特别关注膳食补充剂作为处理肠道炎症的替代非药物方法的潜力。为此,本研究评估了鱼胶原蛋白肽 NaticolGut 对结肠炎症的作用。

方法

野生型和髓系 Mannose 受体缺陷型 C57BL/6 小鼠给予葡聚糖硫酸钠(DSS)、NaticolGut、DSS 和 NaticolGut 或仅水 4 或 8 天。通过建立宏观和微观评分、通过 ELISA 测量细胞因子和钙卫蛋白的产生以及通过化学发光测量髓过氧化物酶活性来评估炎症状态。通过测量特定炎症和氧化状态标志物的 mRNA 水平来对结肠巨噬细胞进行表型分析。通过流式细胞术确定结肠免疫细胞群和 T 细胞激活谱。通过 qPCR 评估粘膜相关肠道微生物群的评估。通过 RT-qPCR 和流式细胞术对来自炎症性肠病(IBD)患者的人血液单核细胞的表型进行特征描述,并通过化学发光法测量其氧化活性。

结果

与仅暴露于 DSS 的小鼠相比,用 NaticolGut 治疗的 DSS 小鼠的结肠炎症减轻。NaticolGut 通过其在被 Mannose 受体识别后将结肠巨噬细胞的极化方向定向为抗炎和抗氧化表型的能力发挥作用。随后,NaticolGut 的传递调节 CD4 T 细胞有利于 Th2 反应并抑制 CD8 T 细胞的激活。这种免疫调节导致肠道生态平衡。在来自 IBD 患者的人单核细胞中,用 NaticolGut 治疗也恢复了抗炎和抗氧化表型。

结论

NaticolGut 作为一种保护剂对抗结肠炎,作为一种新的功能性食品,在肠道健康方面具有创新性和互补性的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c37/9106617/7dc44e76c44d/394_2021_2787_Fig1_HTML.jpg

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