Nanocellulose dysregulated glucose homeostasis in female mice on a Western diet: The role of gut microbiome

Life Sci. 2025 Mar 18:123567. doi: 10.1016/j.lfs.2025.123567. Online ahead of print.

ABSTRACT

There is currently increased interest in nanocellulose as a food emulsifier and dietary supplement. It was hypothesized that nanocellulose could modulate behaviors and glucose homeostasis in female mice using mechanisms of altered gut microbiome and immune modulation. An initial experiment was conducted with the objective of examining whether three common types of nanocellulose affected the gut microbiome of female C57BL/6 mice on a Western diet. Cellulose nanofibrils (CNF), TEMPO-CNF and cellulose nanocrystals were administered at the physiologically relevant dose of 30 mg/kg/day for 30 days by gavage, with cellulose and water groups as the positive and negative controls, respectively. Findings suggested that CNF had the strongest effect on the gut microbiome. CNF was therefore selected for a chronic 6-month study on the gut microbiome, immune system and behaviors in female NOD mice, a model for type 1 diabetes. Gut microbiome analysis suggested that there might be some beneficial changes following subchronic exposure (e.g., at the two-month timepoint), however, this effect was no longer seen after chronic consumption (e.g., at the six-month timepoint). CNF treatment also altered the immune homeostasis, including decreases in the splenic Mac-3⁺ population and serum level of proinflammatory chemokine LIX. Additionally, CNF consumption decreased diabetic incidences but had no effect on the depressive-like behavior and grip strength. However, further analysis, e.g., the insulin tolerance test, indicated that CNF-treated NOD mice might exhibit signs of insulin resistance. Taken together, nanocellulose dysregulated glucose homeostasis in female mice on a Western diet involving mechanisms related to alteration of the gut microbiome.

PMID:40113076 | DOI:10.1016/j.lfs.2025.123567