A Natural Extract Derived from Fish Scales Prevents Type 1 Diabetes in Nonobese Diabetic Mice by Modulating Gut...

Type 1 diabetes (T1D) is a chronic autoimmune disorder characterized by the destruction of pancreatic β-cells and persistent hyperglycemia. The rising global incidence of T1D highlights the need for novel preventive and therapeutic strategies. Fish scale gel (FSG), a marine-derived natural extract rich in collagen peptides, lecithin, unsaturated fatty acids, and chitin, has demonstrated anti-inflammatory and wound-healing properties. However, its potential in modulating the gut microbiota, host metabolism, and pancreatic inflammation during early T1D remains unclear. In this study, nonobese diabetic (NOD) mice were orally administered low, medium, or high doses of FSG for 24 weeks. FSG was well tolerated and significantly reduced random blood glucose levels, improved glucose tolerance, and mitigated body weight loss. Histological and immunohistochemical analyses revealed alleviated islet inflammation and reduced infiltration of immune cells, accompanied by lower expression of interleukin-6 (IL-6) and interferon-γ (IFN-γ). Gut microbiota profiling showed that FSG reversed diabetes-associated dysbiosis by increasing beneficial genera (Anaerofilum, Muribacter, Candidatus Soleaferrea) and decreasing harmful taxa (Anaeromassilibacillus, Gemella, Acetatifactor). This microbial remodeling was accompanied by profound shifts in the serum metabolic profile, which was characterized by an elevation of anti-inflammatory metabolites (glycine, itaconic acid, and ethanolamine) and a reduction in proinflammatory metabolites (glycerol 3-phosphate, behenic acid). Collectively, these findings demonstrate that FSG exerts its protective effects in early-stage T1D by modulating the gut-metabolism-immunity axis, which in turn alleviates local pancreatic inflammation and preserves β-cell function. Therefore, FSG represents a highly promising marine-derived therapeutic candidate for the prevention and management of T1D.