Yao Bo, Liu Jian-Yu, Liu Ying, Song Xiao-Xia, Wang Shi-Bo, Liu Nan, Dong Zhen-Hui, Yuan Zhi-Yong, Han Xiao-Ning, Xing Jin-Yan
Department of Critical Care Medicine, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong, 266035, China; Department of Critical Care Medicine, The Affiliated Hospital of Qingdao University, 1677 Wutaishan Road, Qingdao, Shandong, 266000, China.
Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, 23 Hong Kong East Road, Qingdao, Shandong, 266003, China.
Clin Nutr ESPEN. 2025 Apr;66:245-254. doi: 10.1016/j.clnesp.2025.01.019. Epub 2025 Jan 9.
Gut microbiota disturbance may worsen critical illnesses and is responsible for the progression of multiple organ dysfunction syndrome. In our previous study, there was a trend towards a higher α-diversity of the gut microbiota in sequential feeding (SF) than in continuous feeding (CF) for critically ill patients. We designed this non-blinded, randomized controlled study to confirm these results.
All the enrolled patients received continuous feeding in the beginning. After achieving ≥80 % of the nutrition target calories (25-30 kcal/kg/d), the patients were randomized into the SF group or the CF group. In the SF group, continuous feeding was changed into intermittent feeding. The total daily dosage of enteral nutrition was equally distributed during three periods at 7-9:00, 11-13:00 and 17-19:00. After 7 days of randomization, fresh stool and serum were collected for 16S rRNA gene sequencing and untargeted metabolomics analysis respectively. Meanwhile, routine blood test indicators and metabolic indicators were recorded.
Finally, data from 65 patients in the SF group and 69 patients in the CF group were used for intention-to-treat analysis. There was no difference in the Shannon index between the SF group and CF group [2.5 (1.7-3.4) vs. 2.6 (1.5-3.5), P = 0.934]. However, at the genus level, the abundances of Erysipelotrichaceae_UCG-003 and Howardella increased in the SF group. Some metabolic indicators (the albumin level, total cholesterol level and total bile acid level) and the increases in lymphocyte counts in the SF group were different from those in the CF group (P < 0.05). In untargeted metabolomic analysis, 58 differentially abundant metabolites between the two groups were found. The pathway with the highest enrichment factors was primary bile acid biosynthesis according to the Kyoto Encyclopedia of Genes and Genomes Database classification. Regarding adverse events, the gut tolerance, average glucose and incidence of hyperglycemia and hypoglycemia were similar between the SF group and CF group. The mortality rate in the SF group was lower than that in the CF group, but there was no statistical difference (9.2 % vs. 13.0 %, P = 0.484).
SF did not increase the diversity of gut microbiota in critically ill patients. However, it did alter the abundances of some gut microbes and affect some metabolites. Its clinical significance requires further exploration. In addition, the gut tolerance and safety of SF were similar to that of CF.
www.
gov, registration number NCT04443335. Registered 21 June, 2020.
肠道微生物群紊乱可能会加重危重症病情，并导致多器官功能障碍综合征的进展。在我们之前的研究中，危重症患者序贯喂养（SF）时肠道微生物群的α多样性有高于持续喂养（CF）的趋势。我们设计了这项非盲法随机对照研究来证实这些结果。
所有入组患者起初均接受持续喂养。在达到营养目标热量（25 - 30千卡/千克/天）的≥80%后，将患者随机分为SF组或CF组。在SF组，持续喂养改为间歇喂养。肠内营养的每日总剂量在7 - 9:00、11 - 13:00和17 - 19:00三个时间段平均分配。随机分组7天后，分别采集新鲜粪便和血清用于16S rRNA基因测序和非靶向代谢组学分析。同时，记录常规血液检测指标和代谢指标。
最后，SF组65例患者和CF组69例患者的数据用于意向性分析。SF组和CF组的香农指数无差异[2.5（1.7 - 3.4）对2.6（1.5 - 3.5），P = 0.934]。然而，在属水平上，SF组中丹毒丝菌科_UCG - 003和霍氏菌属的丰度增加。SF组的一些代谢指标（白蛋白水平、总胆固醇水平和总胆汁酸水平）以及淋巴细胞计数的增加与CF组不同（P < 0.05）。在非靶向代谢组学分析中，发现两组间有58种差异丰富的代谢物。根据京都基因与基因组百科全书数据库分类，富集因子最高的途径是初级胆汁酸生物合成。关于不良事件，SF组和CF组的肠道耐受性、平均血糖以及高血糖和低血糖的发生率相似。SF组的死亡率低于CF组，但无统计学差异（9.2%对13.0%，P = 0.484）。
SF未增加危重症患者肠道微生物群的多样性。然而，它确实改变了一些肠道微生物的丰度并影响了一些代谢物。其临床意义需要进一步探索。此外，SF的肠道耐受性和安全性与CF相似。
