## 4 Discussion
In addition, the DSS treatment decreased the relative abundance of _Parsutterella_, which was improved by GP supplement. As a core component in humans and mice, _Parsutterella_ has been defined to be correlated with bile acid maintenance and hypoxanthine metabolism [37]. In the DSS-induced colitis model, hypoxanthine modulated the energy balance of intestinal epithelium and exhibited an improving effect on intestinal barrier function [38]. Therefore, the elevated level of _Parsutterella_ in GP treatment may exert beneficial effects on IBD as well as mucosal homeostasis. Furthermore, the intake of GP showed to decrease in the relative abundances of _Saccharibacteria_, _Bifidobacterium_, and _Peptococcus_ than the DSS treatment. In the saliva microbiota dysbiosis from IBD patients, the _Saccharibacteria_ along with another genus of _Absconditobacteria_, _Leptotrichia_, all were improved compared with healthy controls [39], whereas few studies have ever reported the change of _Saccharibacteria_ in gut intestinal. GP supplement interferes with the abundance of _Akkermansia_, _Peptococcus_, _Bifidobacterium_, _Betaproteobacteria_, _Parsutterella_, _Saccharibacteria_ along with the relieving effect on intestinal inflammatory cytokines, which was the first report about the intervention of collagen-derived peptides on IBD. The changes of the gut microbiota-induced metabolism function would be associated with the inflammatory responses and implied that the change of diet would inspire the microbial biological functions depending on the bidirectional communications among the host and gut microbiota. In the current study, the molecule weight of GP was less than 3 kDa, and most of the peptides were constituted by 7-15 amino acids. In vitro, the GP was treated with RAW264.7 macrophage cells with the investigation on its anti-inflammatory effect. Based on our knowledge, the treatment of GP showed suppressing effect on NO, TNF-\(\alpha\), IL-6, and IL-1\(\beta\)in the cells. However, during the intestinal digestion in vivo, the peptides chain would be destroyed by the digestive enzymes. Thus, the anti-inflammatory properties of GP in vitro could not indicate their activity once being digested and absorbed into the body. Thus, the animal trials were necessary to demonstrate the inflammatory regulating effect of GP. In the DSS induced colitis mice, the GP indeed exhibited a reduction on the inflammatory cytokines as well as improving the tight junctions of the colon. Known from the relative abundances change of gut microbiota, we speculated that some of the peptides in GP would escape from the digestive enzymes to reach the colon tissue. In addition, the peptides could also regulate the reactive oxygen species level in the gut and then exhibit the alleviating effect on the dysbiosis of gut homeostasis [40]. In general, the current research was the first study on the anti-inflammatory effect of bovine bone gelatin-derived peptides with their relieving functionality on IBD. According to the expression of the biomarkers in the colon, the dose of 300 mg/kg/day in GP-2 groups was much more effective than the GP-1 of 100 mg/kg/day. According to the study by [PERSON], the dose in the animal trials could be converted to human equivalent dose by the body surface area normalization method [41]. Thus, the dose of 300 mg/kg/day in mice was converted to 24.32 mg/kg/day for humans (60 kg) and the potential clinical applicable dosage of GP was suggested to be 1459 mg/day.