Khare Sangeeta, DeLoid Glen M, Molina Ramon M, Gokulan Kuppan, Couvillion Sneha P, Bloodsworth Kent J, Eder Elizabeth K, Wong Allison R, Hoyt David W, Bramer Lisa M, Metz Thomas O, Thrall Brian D, Brain Joseph D, Demokritou Philip
Division of Microbiology, National Center for Toxicological Research, U.S. Food & Drug Administration, Jefferson, AR 72079, USA.
Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
NanoImpact. 2020 Apr;18. doi: 10.1016/j.impact.2020.100216. Epub 2020 Feb 28.
Micron scale cellulose materials are "generally regarded as safe" (GRAS) as binders and thickeners in food products. However, nanocellulose materials, which have unique properties that can improve food quality and safety, have not received US-Food and Drug Administration (FDA) approval as food ingredients. and toxicological studies of ingested nanocellulose revealed minimal cytotoxicity, and no subacute toxicity. However, ingested materials may modulate gut microbial populations, or alter aspects of intestinal function not elucidated by toxicity testing, which could have important health implications. Here, we report the results of studies conducted in a rat gavage model to assess the effects of ingested cellulose nanofibrils (CNF) on the fecal microbiome and metabolome, intestinal epithelial expression of cell junction genes, and ileal cytokine production. Feces, plasma, and ilea were collected from Wistar Han rats before and after five weeks of biweekly gavages with water or cream, with or without 1% CNF. CNF altered microbial diversity, and diminished specific species that produce short chain fatty acids, and that are associated with increased serum insulin and IgA production. CNF had few effects on the fecal metabolome, with significant changes in only ten metabolites of 366 measured. Exposure to CNF also altered expression of epithelial cell junction genes, and increased production of cytokines that modulate proliferation of CD8 T cells. These perturbations likely represent initiation of an adaptive immune response, however, no associated pathology was seen within the duration of the study. Additional studies are needed to better understand the health implications of these changes in long term.
微米级纤维素材料作为食品中的粘合剂和增稠剂“一般被认为是安全的”（GRAS）。然而，具有能改善食品质量和安全性的独特特性的纳米纤维素材料，尚未获得美国食品药品监督管理局（FDA）作为食品成分的批准。对摄入的纳米纤维素的毒理学研究显示细胞毒性极小，且无亚急性毒性。然而，摄入的物质可能会调节肠道微生物群，或改变毒性测试未阐明的肠道功能方面，这可能对健康有重要影响。在此，我们报告在大鼠灌胃模型中进行的研究结果，以评估摄入的纤维素纳米纤维（CNF）对粪便微生物组和代谢组、细胞连接基因的肠上皮表达以及回肠细胞因子产生的影响。在对Wistar Han大鼠进行为期五周、每两周一次用水或乳膏灌胃（含或不含1% CNF）之前和之后，收集其粪便、血浆和回肠。CNF改变了微生物多样性，减少了产生短链脂肪酸且与血清胰岛素和IgA产生增加相关的特定物种。CNF对粪便代谢组影响很小，在测量的366种代谢物中只有10种有显著变化。接触CNF还改变了上皮细胞连接基因的表达，并增加了调节CD8 T细胞增殖的细胞因子的产生。这些扰动可能代表适应性免疫反应的启动，然而，在研究期间未观察到相关病理学变化。需要进一步研究以更好地理解这些变化在长期内对健康的影响。
