Modulation of Gut Microbiota and Intestinal Barrier Integrity and Inflammation Profile in High Fat-fed Rats

Gut microbiota dysbiosis and consequent dysregulation of the intestinal barrier homeostasis have been implicated in the development of metabolic complications. Korean red ginseng (RG) and its fermented RG (bio-transformed by microorganism, FRG) have been recognized for their prebiotic role in the regulation of intestinal barrier function and inflammation. Thus, we investigated the effects of RG and FRG supplementation on gut barrier integrity and inflammatory profile in association with the compositional change in the gut microbiota of rats fed a high-fat (HF) diet. Male Sprague-Dawley rats (n = 8/group; 6 weeks old) were counterbalanced by initial weight into four groups and fed either a low-fat (LF; 10% kcal as fat), HF (45% kcal as fat), or HF diet supplemented with RG or FRG at 1% (w/w) in diet for 6 weeks. RG and FRG supplementation led to compositional shifts in the gut microbiota characterized by Eubacterium by RG and Akkermansia genus by FRG, which have been associated with improved obese phenotype and glucose homeostasis. These changes were associated with improvements in gut barrier integrity, consequently protecting from HF-induced local (colon, liver) and systemic inflammation. RG and FRG supplementation also ameliorated lipopolysaccharide-induced inflammation by inhibiting its downstream pathway. Taken together, these data show that RG and FRG supplementation can improve the gut barrier function and local and systemic inflammation in HF-fed rats in association with compositional changes of the gut microbiota, supporting the promising application of RG and FRG for the regulation of gut barrier integrity and inflammatory profile under a metabolic challenge.