Abstract:
High-fructose diets are strongly associated with the development of metabolic disorders, including obesity, insulin resistance, systemic inflammation, and gut barrier dysfunction. In this study, we provide evidence that Bacillus subtilis SF106 represents an effective probiotic strategy against fructose-induced metabolic alterations, with beneficial effects observed exclusively when administered in its spore form, while vegetative cells were ineffective. SF106 spores exert a marked anti-obesogenic effect by modulating lipid metabolism. Despite similar caloric intake, fructose-fed rats showed increased body lipid accumulation and visceral adipose tissue expansion, associated with reduced lipid oxidation. In contrast, spore-treated animals displayed enhanced lipid oxidation, increased energy expenditure, and prevention of fat accumulation. Furthermore, spores preserved glucose homeostasis and insulin sensitivity, maintaining normal glycemic and insulin responses during glucose tolerance tests.
Systemic inflammation induced by fructose feeding, characterized by elevated plasma levels of LPS, TNF-α, and IL-6, was significantly reduced by SF106 spores, which also increased the anti-inflammatory cytokine IL-10. These effects were linked to the preservation of gut barrier integrity, as spores prevented the reduction of tight junction proteins and limited endotoxin translocation. Mechanistically, this protection was associated with the ability of SF106 spores to counteract oxidative stress in the ileum, maintaining redox balance and supporting proper cellular function. Spore supplementation also induced significant changes in gut microbiota composition, unlike vegetative cells. In particular, the restoration of Eubacterium fissicatena, a taxon negatively associated with obesity and metabolic dysfunction, suggests a microbiota-mediated contribution to the observed metabolic improvements.
At the tissue level, SF106 spores preserved skeletal muscle mitochondrial function, preventing oxidative damage and ectopic lipid deposition induced by fructose. In parallel, they counteracted the “whitening” of subcutaneous adipose tissue by promoting browning processes, as indicated by increased expression of thermogenic markers such as UCP-1 and PGC1-α. These effects were associated with microbiota-dependent modulation of bile acid metabolism, including increased levels of secondary bile acids such as UDCA and CDCA, which are known to activate thermogenic pathways and improve metabolic homeostasis.
Overall, our findings demonstrate that Bacillus subtilis SF106 spores act through multiple, coordinated mechanisms involving gut integrity, systemic inflammation, microbiota composition, mitochondrial function, and adipose tissue remodeling. These results highlight the importance of spore-based probiotic formulations and support their potential use as a therapeutic strategy against fructose-induced metabolic disorders.
