# Effects of Potential Prebiotics from _Codium fragile_ on Intestinal Diseases
## 4 Discussion  
Sulfated polysaccharides derived from seaweed can be used as prebiotics for gut microorganisms and degraded into other bioactive compounds, such as oligosaccharides, phytochemicals, and SCFAs, which can serve as substrates for these organisms and allow them to grow [36; 37; 38; 39; 40]. Sulfated galactan from _C. fragile_ consists of a large amount of galactose residues, with trace arabinose and the presence of pyruvate and sulfate as substituents [7]. Additionally, our previous research reported that CFE comprises many galactose residues, with traces of arabinose and the presence of sulfate as substituents [30]. In the present study, we elucidated the ability of CFE to promote the growth of _A. muciiphila_. The presence of _A. muciiphila_ in feces has been associated with a healthy intestine, and its abundance has been inversely correlated with several disease states. Further analysis confirmed that _A. muciiphila_ can degrade mucin and exert competitive inhibition on other pathogenic bacteria that degrade the mucin [41]. Therefore, the present study aimed to investigate the efficacy and underlying mechanisms of CFE in alleviating DSS-induced colitis in mice. The proliferation of bacteria during 10 weeks of CFE feeding was determined using quantitative PCR. As the administration of CFE increased, the proliferation of probiotics increased whereas the proliferation of pathogenic bacteria decreased. Therefore, our results indicate that CFE can be used as a prebiotic material. Moreover, _A. muciiphila_ significantly increased in the HCEF group. _A. muciiphila_ is abundant in the gut microbiota of healthy individuals, and it is beneficial in the prevention and treatment of obesity, type 2 diabetes, and other metabolic dysfunctions [18; 19; 20; 21; 42; 43; 44; 45]. Therefore, CFE can be used as a prebiotic that specifically promotes _A. muciiphila_ growth for the treatment of metabolic diseases. After CFE administration for 10 weeks, acetic acid was identified as the major metabolite in mouse cecum. A similar result was also reported by [PERSON] et al. [46], who found that acetic acid was a major metabolite produced by _A. muciiphila_ in static and dynamic cultures. [PERSON] et al. [46] reported that acetic acid increased lipolysis and decreased lipid synthesis in BRL-3A cells, thus reducing the accumulation of hepatic fat in BRL-3A cells. Therefore, CFE was thought to reduce lipid synthesis as it led to the production of acetic acid by promoting the growth of _A. muciiphila_. \(\beta\)-Glucuronidase activity is a major factor in causing colon cancer [47]. \(\beta\)-Glucuronidase hydrolyzes \(\beta\)-D-glucuronides to glucuronic acid and aglycone, such as alcohol, amine, urine, or a thiol compound. UDP-glucuronosyltransferase catalyzes glucuronide formation. From the liver, where synthesis occurs, it is partially eliminated into the large intestines along with bile. There, it is hydrolyzed to aglycone under the influence of bacterial \(\beta\)-glucuronidase, which is further hydrolyzed to aglycones. High \(\beta\)-glucuronidase activity  
Figure 4: CFE prevented DSS-induced colon damage in mice. (**a**) H&E staining of colon, magnification \(\times 100\), (**b**) Histology score, (**c**) MPO (myleoperoxidase) activity. The data shown are the mean \(\pm\) SD of five independent experiments. Significant differences are noted as \({}^{\#\#\#}\)\(p<0.05\) compared with the normal group and \({}^{\star}\)\(p<0.05\), \({}^{\star\#}\)\(p<0.01\), and \({}^{\star\#\#}\)\(p<0.001\) compared with the negative control group. was observed in patients diagnosed with colonic neoplasia, suggesting that this enzyme plays an important role in promoting colonic neoplasia [48]. During the adaptation period, all mice were fed the AIN-93 diet for 1 week, but the enzymatic activity in each group at week 0 was not the same because the large intestines of all mice form a complex microbial ecosystem.