Enrichment of Short-Chain Fatty Acid-Producing Bacteria by pH-Responsive Sodium Alginate and Chitosan-Encapsulated Quercetin

Tianlong Liu^1*Qianyu Bai¹Zhongling Zhao²Yujing Duan³Runqiu Cai¹Yinzhu Chen¹Chaoyu Zhou¹Xinyuan Tian¹Yifei Yang¹Haiyan Wu¹Mingju Li⁴Jia You⁵Qingyi Song⁶Hong Dong^2*

• ¹China Agricultural University, Beijing, China
• ²Beijing University of Agriculture, Beijing, Beijing Municipality, China
• ³Beijing Wildlife Park, Beijing, China
• ⁴Yantai Animal Disease Control Center, Yantai, China
• ⁵Yantai Agricultural Technology Extension Center, Yantai, China
• ⁶Anyang Zhongnongda Biotechnology Co., Ltd, Anyang, China

Conventional approaches to treat ulcerative colitis (UC) focus on suppressing excessive inflammation and immune responses. Nevertheless, these treatments fail to address gut dysbiosis or restore the intestinal mucosal barrier effectively. Regulating the intestinal microenvironment may be pivotal to more effective therapies for UC. Herein, oral co-lon-targeted microspheres, sodium alginate-chitosanencapsulate quercetin (SA-Q-CS MPs), were developed. SA-Q-CS MPs markedly enhanced the overall richness and diversity of the gut microbiota, enhancing the abundance of short-chain fatty acids (SCFAs)-producing bacteria, such as Bacteroidales, Lactobacillales, and Lachnospiraceae. These changes contributed to improved intestinal barrier function, better metabolic processes, and stronger defense mechanisms, thereby ameliorating UC induced by 3% dextran sulfate sodium (DSS) in C57BL/6J mice. Compared to the DSS group, the SA-Q-CS MPs treatment group showed significant improvements, with the Disease Activity Index (DAI) and histopathological scores reduced by more than 66.9%, pro-inflammatory factor levels decreased by 65%, antioxidant levels increased over sevenfold, and tight junction protein expression elevated by more than threefold. In conclusion, this investigation presents SA-Q-CS MPs as a promising strategy for restoring gut microbiome homeostasis and providing precise treatment for UC.