Tian Sangshan, Goand Umesh K, Paudel Devendra, Le Giang V, Tiwari Amit K, Prabhu K Sandeep, Singh Vishal
The Pennsylvania State University.
University of Arkansas for Medical Sciences.
Res Sq. 2024 Dec 9:rs.3.rs-5522559. doi: 10.21203/rs.3.rs-5522559/v1.
The vital role of naturally occurring dietary fibers (DFs) in maintaining intestinal health has fueled the incorporation of isolated DFs into processed foods. A select group of soluble DFs, such as partially hydrolyzed guar gum (Phgg), are being promoted as dietary supplements to meet recommended DF intake. However, the potential effects of regular consumption of these processed DFs on gastrointestinal health remain largely unknown. The present study assessed the impact of Phgg on the development of intestinal inflammation and colitis-associated colon carcinogenesis (CAC). Wild-type C57BL/6 mice were fed isocaloric diets containing either 7.5% Phgg and 2.5% cellulose (Phgg group) or 10% cellulose (control) for four weeks. To induce colitis, a subgroup of mice from each group was switched to 1.4% dextran sulfate sodium (DSS) in drinking water for seven days. CAC was induced in another subgroup through a single dose of azoxymethane (AOM, 7.5 mg/kg i.p.) followed by three DSS/water cycles. To our surprise, Phgg feeding exacerbated DSS-induced colitis, as evidenced by body weight loss, disrupted colonic crypt architecture, and increased pro-inflammatory markers accompanied by a decrease in anti-inflammatory markers. Additionally, Phgg feeding led to increased colonic expression of genes promoting cell proliferation. Accordingly, extensive colon tumorigenesis was observed in Phgg-fed mice in the AOM/DSS model, whereas the control group exhibited no visible tumors. To investigate whether reducing Phgg has a distinct effect on colitis and CAC development, mice were fed a low-Phgg diet (2.5% Phgg). The low-Phgg group also exhibited increased colitis and tumorigenesis compared to the control, although the severity was markedly lower than in the regular Phgg (7.5%) group, suggesting a dose-dependent effect of Phgg in colitis and CAC development. Our study reveals that Phgg supplementation exacerbates colitis and promotes colon tumorigenesis, warranting further investigation into the potential gastrointestinal health risks associated with processed Phgg consumption.
天然膳食纤维（DFs）在维持肠道健康方面的重要作用推动了将分离出的膳食纤维添加到加工食品中。一组特定的可溶性膳食纤维，如部分水解瓜尔胶（Phgg），正作为膳食补充剂被推广，以满足推荐的膳食纤维摄入量。然而，经常食用这些加工后的膳食纤维对胃肠道健康的潜在影响在很大程度上仍不为人知。本研究评估了Phgg对肠道炎症发展和结肠炎相关结肠癌发生（CAC）的影响。给野生型C57BL/6小鼠喂食含7.5% Phgg和2.5%纤维素的等热量饮食（Phgg组）或10%纤维素饮食（对照组），持续四周。为诱导结肠炎，每组的一个亚组小鼠改为饮用含1.4%葡聚糖硫酸钠（DSS）的水，持续七天。通过单次腹腔注射氧化偶氮甲烷（AOM，7.5 mg/kg），随后进行三个DSS/水周期，在另一个亚组中诱导CAC。令我们惊讶的是，喂食Phgg加剧了DSS诱导的结肠炎，表现为体重减轻、结肠隐窝结构破坏、促炎标志物增加以及抗炎标志物减少。此外，喂食Phgg导致促进细胞增殖的基因在结肠中的表达增加。因此，在AOM/DSS模型中，喂食Phgg的小鼠出现了广泛的结肠肿瘤发生，而对照组未观察到明显肿瘤。为研究减少Phgg是否对结肠炎和CAC发展有不同影响，给小鼠喂食低Phgg饮食（2.5% Phgg）。与对照组相比，低Phgg组也表现出结肠炎和肿瘤发生增加，尽管严重程度明显低于常规Phgg（7.5%）组，这表明Phgg在结肠炎和CAC发展中存在剂量依赖性效应。我们的研究表明，补充Phgg会加剧结肠炎并促进结肠肿瘤发生，有必要进一步研究与食用加工后的Phgg相关的潜在胃肠道健康风险。
