Abstract
Background: High-fat diet (HFD)-induced hepatic inflammation impairs liver function, promotes fibrosis, and may progress to hepatocellular carcinoma, thereby posing a significant threat to human health. Meanwhile, fermented whole grains have attracted growing attention owing to their diverse beneficial biological properties. Methods: In this study, we investigated the effects of co-fermented quinoa and black barley (FG) on HFD-induced chronic hepatic inflammation using male C57BL/6J mice. Results: FG intervention significantly attenuated excessive body weight gain and reduced hepatic adipose accumulation in HFD-fed mice. Furthermore, FG alleviated hepatic inflammation by downregulating the transcriptional and protein levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), as well as the transcriptional levels of toll-like receptor 4 (Tlr4), cluster of differentiation 14 (CD14), and myeloid differentiation primary response gene 88 (Myd88). Metabolomic analysis identified several hepatic and fecal metabolites, such as vitamin A and L-tryptophan, that were upregulated by FG treatment. The strong negative correlation of these metabolites with hepatic inflammatory markers suggests their role as putative mediators of FG's anti-inflammatory action. Additionally, FG enhanced the relative abundances of probiotic taxa, including g_Lawsonibacter, g_Acetatifactor, and s_Bifidobacterium cricetid, and upregulated the microbial bile acid (BA) biosynthesis pathway. Notably, these enriched probiotics exhibited a positive correlation with the aforementioned fecal metabolites. Conclusions: Our findings suggest that FG has the potential to alleviate HFD-induced hepatic inflammation by restoring gut microbiota imbalance and reversing metabolic disorders.