Yang Jieping, Germano Patrizia Maria, Oh Suwan, Wang Sijia, Wang Jing, Lee Rupo, Paige Hayden, Yang Scarlet, Henning Susanne M, Zhong Jin, Jacobs Jonathan P, Li Zhaoping
Center for Human Nutrition, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
Department of Medicine at the David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Mol Nutr Food Res. 2022 Mar;66(5):e2100730. doi: 10.1002/mnfr.202100730. Epub 2022 Jan 5.
The study tests the hypothesis that dietary pomegranate extract (PomX) supplementation attenuates colitis in a Western diet feed IL-10 deficient (IL-10-/-) murine model.
Four-week-old male IL-10-/- mice are randomly assigned to a high fat high sucrose (HFHS) diet or a HFHS diet supplement with 0.25% PomX for 8 weeks. PomX supplementation lead to significantly lower histological score for colitis (2.6 ± 0.5 vs 3.9 ± 1.0), lower spleen weight (0.11 ± 0.01 vs 0.15 ± 0.02), and lower circulating Interleukin 6(IL-6) levels (15.8±2.2 vs 29.5±5.5) compared with HFHS fed controls. RNAseq analysis of colonic tissues showed 483 downregulated and 263 upregulated genes with PomX supplementation, which are mainly associated with inflammatory responses, defenses, and neutrophil degranulation. In addition, PomX treatment affects the cecal microbiome with increased alpha diversity, altered microbial composition, and increased levels of the tryptophan-related microbial metabolite indole propionate.
The data demonstrate that dietary PomX supplementation ameliorated colitis and lowered inflammatory markers in HFHS fed IL-10-/- mice. These data support the anti-inflammatory effects of dietary PomX supplementation for IBD and a potential mediating role of gut microbiome, suggesting the need for future clinical studies to explore the use of PomX dietary supplementation in IBD patients.
本研究检验了以下假设：在西方饮食喂养的白细胞介素-10缺陷（IL-10-/-）小鼠模型中，膳食补充石榴提取物（PomX）可减轻结肠炎。
将4周龄雄性IL-10-/-小鼠随机分为高脂高糖（HFHS）饮食组或添加0.25% PomX的HFHS饮食组，持续8周。与喂食HFHS的对照组相比，补充PomX导致结肠炎的组织学评分显著降低（2.6±0.5对3.9±1.0），脾脏重量降低（0.11±0.01对0.15±0.02），循环白细胞介素6（IL-6）水平降低（15.8±2.2对29.5±5.5）。结肠组织的RNA测序分析显示，补充PomX后有483个基因下调，263个基因上调，这些基因主要与炎症反应、防御和中性粒细胞脱颗粒有关。此外，PomX处理影响盲肠微生物群，增加了α多样性，改变了微生物组成，并增加了色氨酸相关微生物代谢产物吲哚丙酸的水平。
数据表明，膳食补充PomX可改善HFHS喂养的IL-10-/-小鼠的结肠炎并降低炎症标志物。这些数据支持膳食补充PomX对炎症性肠病的抗炎作用以及肠道微生物群的潜在介导作用，提示未来需要进行临床研究以探索PomX膳食补充剂在炎症性肠病患者中的应用。
