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. In vitro and in vivo toxicological studies of ingested nanocellulose revealed minimal cytotoxicity, and no subacute in vivo 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.
Keywords: in vivo; ingested nanomaterial; intestinal permeability; metabolome; microbiome; nanocellulose; rat; risk assessment.