Objective To investigate the structural characteristics of intestinal flora in children with sepsis and its association with inflammatory response. Methods A prospective cohort study was conducted. The children with sepsis who were admitted from December 2021 to January 2023 were enrolled as the sepsis group, and the children with non-sepsis who were admitted during the same period were enrolled as the non-sepsis group. The two groups were compared in terms of the distribution characteristics of intestinal flora, peripheral white blood cell count (WBC), C reactive protein (CRP), and cytokines, and the correlation of the relative abundance of fecal flora with WBC, CRP, and cytokines was analyzed. Results At the genus level, compared with the non-sepsis group, the sepsis group had significantly lower relative abundance of Akkermansia, Ruminococcus, and Alistipes and significantly higher relative abundance of Enterococcus, Streptococcus, and Staphylococcus (P<0.05). At the phylum level, Proteobacteria was the dominant phylum (37.46%) in the group of children with a score of ≤70 from the Pediatric Critical Illness Score (PICS), and Firmicutes was the dominant phylum in the group of children with a score of 71-80 or 81-90 from the PICS (72.20% and 43.88%, respectively). At the genus level, among the 18 specimens, 5 had a relative abundance of >50% for a single flora. Compared with the non-sepsis group, the sepsis group had significant higher levels of WBC, CRP, interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (P<0.05). The Spearman's rank correlation analysis showed that at the genus level, the relative abundance of Ruminococcus, Alistipes, and Parasutterella in the sepsis group was negatively correlated with the levels of WBC, CRP, and IL-6 (P<0.05); the relative abundance of Enterococcus was positively correlated with the CRP level (P<0.01); the relative abundance of Streptococcus and Staphylococcus was positively correlated with the levels of CRP and IL-6 (P<0.05); the relative abundance of Streptococcus was positively correlated with WBC (P<0.05). Conclusions Intestinal flora disturbance is observed in children with sepsis, and its characteristics vary with the severity of the disease. The structural changes of intestinal flora are correlated with inflammatory response in children with sepsis.
Key words
Sepsis /
Intestinal flora /
Inflammatory response /
Correlation /
Child
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References
1 de Castro REV, Medeiros DNM, Prata-Barbosa A, et al. Surviving Sepsis Campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children[J]. Pediatr Crit Care Med, 2020, 21(10): 924-925. PMID: 33009314. DOI: 10.1097/PCC.0000000000002444.
2 Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the global burden of disease study[J]. Lancet, 2020, 395(10219): 200-211. PMID: 31954465. PMCID: PMC6970225. DOI: 10.1016/S0140-6736(19)32989-7.
3 钱寒, 殷凡, 宁铂涛. 脓毒症期间T细胞亚群在主要免疫器官内的变化[J]. 中国小儿急救医学, 2022, 29(3): 199-205. DOI: 10.3760/cma.j.issn.1673-4912.2022.03.009.
4 Haak BW, Wiersinga WJ. The role of the gut microbiota in sepsis[J]. Lancet Gastroenterol Hepatol, 2017, 2(2): 135-143. PMID: 28403983. DOI: 10.1016/S2468-1253(16)30119-4.
5 李燕, 陆斯良, 莫艳, 等. 神经发育损害早产儿肠道菌群变化的前瞻性队列研究[J]. 中国当代儿科杂志, 2023, 25(7): 689-696. PMID: 37529950. PMCID: PMC10414177. DOI: 10.7499/j.issn.1008-8830.2302130.
6 刘智程, 吴德, 屈爱娜, 等. 孤独症谱系障碍儿童肠道菌群多样性研究及功能预测分析[J]. 中国当代儿科杂志, 2022, 24(12): 1356-1364. PMID: 36544419. PMCID: PMC9785081. DOI: 10.7499/j.issn.1008-8830.2207130.
7 Adelman MW, Woodworth MH, Langelier C, et al. The gut microbiome's role in the development, maintenance, and outcomes of sepsis[J]. Crit Care, 2020, 24(1): 278. PMID: 32487252. PMCID: PMC7266132. DOI: 10.1186/s13054-020-02989-1.
8 Liu W, Cheng M, Li J, et al. Classification of the gut microbiota of patients in intensive care units during development of sepsis and septic shock[J]. Genomics Proteomics Bioinformatics, 2020, 18(6): 696-707. PMID: 33607294. PMCID: PMC8377022. DOI: 10.1016/j.gpb.2020.06.011.
9 Haussner F, Chakraborty S, Halbgebauer R, et al. Challenge to the intestinal mucosa during sepsis[J]. Front Immunol, 2019, 10: 891. PMID: 31114571. PMCID: PMC6502990. DOI: 10.3389/fimmu.2019.00891.
10 Liu J, Wang M, Chen W, et al. Altered gut microbiota taxonomic compositions of patients with sepsis in a pediatric intensive care unit[J]. Front Pediatr, 2021, 9: 645060. PMID: 33898360. PMCID: PMC8058355. DOI: 10.3389/fped.2021.645060.
11 喻坤, 颜海鹏, 卢秀兰, 等. 细胞因子免疫分型对脓毒症患儿病情及预后的评价作用[J]. 中国小儿急救医学, 2021, 28(6): 468-471. DOI: 10.3760/cma.j.issn.1673-4912.2021.06.006.
12 Chen Y, Zhang F, Ye X, et al. Association between gut dysbiosis and sepsis-induced myocardial dysfunction in patients with sepsis or septic shock[J]. Front Cell Infect Microbiol, 2022, 12: 857035. PMID: 35372123. PMCID: PMC8964439. DOI: 10.3389/fcimb.2022.857035.
13 Wan YD, Zhu RX, Wu ZQ, et al. Gut microbiota disruption in septic shock patients: a pilot study[J]. Med Sci Monit, 2018, 24: 8639-8646. PMID: 30488879. PMCID: PMC6282651. DOI: 10.12659/MSM.911768.
14 Yang XJ, Liu D, Ren HY, et al. Effects of sepsis and its treatment measures on intestinal flora structure in critical care patients[J]. World J Gastroenterol, 2021, 27(19): 2376-2393. PMID: 34040329. PMCID: PMC8130038. DOI: 10.3748/wjg.v27.i19.2376.
15 刘丹, 王晓红, 张小彬, 等. 脓毒症患者肠道菌群紊乱的临床研究[J]. 中华急诊医学杂志, 2019, 28(6): 736-742. DOI: 10.3760/cma.j.issn.1671-0282.2019.06.015.
16 Lin X, Abdalla M, Yang J, et al. Relationship between gut microbiota dysbiosis and immune indicator in children with sepsis[J]. BMC Pediatr, 2023, 23(1): 516. PMID: 37845615. PMCID: PMC10578006. DOI: 10.1186/s12887-023-04349-8.
17 杨小娟, 杨晓军, 刘丹, 等. 脓毒症患者肠道菌群与肠屏障功能紊乱的相关性研究[J]. 中华急诊医学杂志, 2022, 31(2): 210-216. DOI: 10.3760/cma.j.issn.1671-0282.2022.02.013.
18 Niu M, Chen P. Crosstalk between gut microbiota and sepsis[J]. Burns Trauma, 2021, 9: tkab036. PMID: 34712743. PMCID: PMC8547143. DOI: 10.1093/burnst/tkab036.
19 Lankelma JM, van Vught LA, Belzer C, et al. Critically ill patients demonstrate large interpersonal variation in intestinal microbiota dysregulation: a pilot study[J]. Intensive Care Med, 2017, 43(1): 59-68. PMID: 27837233. PMCID: PMC5203863. DOI: 10.1007/s00134-016-4613-z.
20 Dickson RP, Singer BH, Newstead MW, et al. Enrichment of the lung microbiome with gut bacteria in sepsis and the acute respiratory distress syndrome[J]. Nat Microbiol, 2016, 1(10): 16113. PMID: 27670109. PMCID: PMC5076472. DOI: 10.1038/nmicrobiol.2016.113.
21 Miller WD, Keskey R, Alverdy JC. Sepsis and the microbiome: a vicious cycle[J]. J Infect Dis, 2021, 223(12 Suppl 2): S264-S269. PMID: 33330900. PMCID: PMC8206800. DOI: 10.1093/infdis/jiaa682.
22 Schirmer M, Smeekens SP, Vlamakis H, et al. Linking the human gut microbiome to inflammatory cytokine production capacity[J]. Cell, 2016, 167(4): 1125-1136.e8. PMID: 27814509. PMCID: PMC5131922. DOI: 10.1016/j.cell.2016.10.020.
23 Xie S, Li J, Lyu F, et al. Novel tripeptide RKH derived from Akkermansia muciniphila protects against lethal sepsis[J]. Gut, 2023, 73(1): 78-91. PMID: 37553229. DOI: 10.1136/gutjnl-2023-329996.
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