Haifeng Sun1, Jingcheng Bi2, Qiucheng Lei3, Xiao Wan4, Tingting Jiang5, Chao Wu6, Xinying Wang7. 1. Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China. 2. Department of Thyroid and Breast Surgery, Taizhou People's Hospital, Taizhou 225300, Jiangsu Province, China. 3. Department of Liver Surgery, The First People's Hospital of Foshan, Foshan 528000, Guangdong Province, China. 4. Anhui Provincial Hospital, Hefei 230001, Anhui Province, China. 5. Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China. 6. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. 7. Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China. Electronic address: wangxinying@nju.edu.cn.
Abstract
BACKGROUND AND AIMS: Partial enteral nutrition (PEN) protects parenteral nutrition (PN) induced gut mucosal immunity impairment. However, the gastrointestinal function of most patients with PN is too poor to tolerate full dosage of PEN and no guidelines recommend PEN dose. We aimed to identify an optimal PEN dose and to understand the protective mechanism. METHODS: Mice were assigned to groups with total parenteral nutrition (TPN), total enteral nutrition (TEN), or various degrees of PEN with PN. Additionally, AS1517499 was used to inhibit STAT6. Five days after treatment, secretory immunoglobulin A (sIgA) levels of luminal washing fluid and JAK1-STAT6 signalling in ileum tissue of different groups were assessed. RESULTS: We found that TPN lowered luminal sIgA and down-regulated pIgR, phosphorylated JAK1 and STAT6, IL-4 and IL-13 as well relative to TEN. Moreover, 40% EN were lowest dose that reversed these detrimental consequences of PN to an equivalent level as TEN. The rescue of pIgR and luminal sIgA expression was decreased when the JAK1-STAT6 pathway was inhibited. CONCLUSION: We conclude that 40% EN is the optimal PEN dose that reverses PN-induced impairment of gut mucosal immunity. Additionally, we hypothesise that this benefit involves activation of the JAK1-STAT6 pathway.
BACKGROUND AND AIMS: Partial enteral nutrition (PEN) protects parenteral nutrition (PN) induced gut mucosal immunity impairment. However, the gastrointestinal function of most patients with PN is too poor to tolerate full dosage of PEN and no guidelines recommend PEN dose. We aimed to identify an optimal PEN dose and to understand the protective mechanism. METHODS:Mice were assigned to groups with total parenteral nutrition (TPN), total enteral nutrition (TEN), or various degrees of PEN with PN. Additionally, AS1517499 was used to inhibit STAT6. Five days after treatment, secretory immunoglobulin A (sIgA) levels of luminal washing fluid and JAK1-STAT6 signalling in ileum tissue of different groups were assessed. RESULTS: We found that TPN lowered luminal sIgA and down-regulated pIgR, phosphorylated JAK1 and STAT6, IL-4 and IL-13 as well relative to TEN. Moreover, 40% EN were lowest dose that reversed these detrimental consequences of PN to an equivalent level as TEN. The rescue of pIgR and luminal sIgA expression was decreased when the JAK1-STAT6 pathway was inhibited. CONCLUSION: We conclude that 40% EN is the optimal PEN dose that reverses PN-induced impairment of gut mucosal immunity. Additionally, we hypothesise that this benefit involves activation of the JAK1-STAT6 pathway.