Co-Fermented Black Barley and Quinoa Alleviate Hepatic Inflammation via Regulating Metabolic Disorders and Gut Microbiota in Mice Fed with High-Fat Diet

<b>Background</b>: 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. <b>Methods</b>: 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. <b>Results:</b> 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 (<i>Tlr4</i>), cluster of differentiation 14 (<i>CD14</i>), and myeloid differentiation primary response gene 88 (<i>Myd88</i>). 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 <i>g_Lawsonibacter</i>, <i>g_Acetatifactor</i>, and <i>s_Bifidobacterium cricetid</i>, and upregulated the microbial bile acid (BA) biosynthesis pathway. Notably, these enriched probiotics exhibited a positive correlation with the aforementioned fecal metabolites. <b>Conclusions</b>: Our findings suggest that FG has the potential to alleviate HFD-induced hepatic inflammation by restoring gut microbiota imbalance and reversing metabolic disorders.