肠易激综合征患者肠道菌群变化与神经内分泌轴功能、炎症因子的关系

The relationship of gut microbiota changes with neuroendocrine axis function and inflammatory factors in patients with irritable bowel syndrome

摘要

目的 分析肠易激综合征患者肠道菌群变化与神经内分泌轴功能、炎症因子的关系,为肠易激综合征的临床诊治提供依据。方法 选取2023年1月—2024年12月河北省保定市第二中心医院收治的肠易激综合征患者120例作为研究组,根据病情分为腹泻型（66例）、便秘型（28例）与混合型（26例）,另选同期于医院体检的健康人120例对照组。比较研究组、对照组,不同分型肠易激综合征患者肠道菌群、神经内分泌轴功能及炎症因子,通过Pearson相关分析法分析肠道菌群与下丘脑-垂体-肾上腺轴、甲状腺轴功能、炎症指标的相关性。结果 与对照组比较,研究组双歧杆菌、乳杆菌水平、血清游离甲状腺素（free thyroxine,FT4）、8：00促肾上腺皮质激素（adrenocorticotropic hormone,ACTH）水平更低,肠杆菌、肠球菌、24：00血清ACTH、16：00血清皮质醇（cortisol,Cor）水平,血清总三碘甲状腺原氨酸（total triiodothyronine,T3）、游离三碘甲状腺原氨酸（free triiodothyronine,FT3）、CC趋化因子配体16（C-C motif chemokine ligand 16,CCL16）、白细胞介素17A（interleukin-17A,IL-17A）水平,全血中性粒细胞绝对数（neutrophil absolute count,NEUT）水平更高（P<0.05）。与腹泻型比较,便秘型、混合型双歧杆菌、乳杆菌水平、血清FT4、8：00 ACTH水平更低,肠杆菌、肠球菌、24：00血清ACTH、16：00血清Cor水平、血清T3、FT3、CCL16、IL-17A水平、全血NEUT水平更高（P<0.05）;与便秘型比较,混合型双歧杆菌、乳杆菌水平、血清FT4、8：00 ACTH水平更低,肠杆菌、肠球菌、24：00血清ACTH、16：00血清Cor水平、血清T3、FT3、CCL16、IL-17A水平、全血NEUT水平更高（P<0.05）。Pearson相关分析法结果显示,双歧杆菌、乳杆菌与8：00 ACTH、FT4呈正相关,与24：00 ACTH、16：00血清Cor、T3、FT3、NEUT、CCL16、IL-17A呈负相关;肠杆菌、肠球菌与8：00 ACTH、FT4呈负相关,与24：00 ACTH、16：00 Cor、T3、FT3、NEUT、CCL16、IL-17A呈正相关（P<0.05）。结论 肠易激综合征患者肠道菌群优势菌株发生变化,机体下丘脑-垂体-肾上腺轴、甲状腺轴节律紊乱,腹泻型、便秘型、混合型指标变化呈增加趋势,且肠道菌群变化与神经内分泌轴功能、炎症因子密切相关。

Abstract

Objective To analyze the relationship of the gut microbiota changes and the functions of the neuroendocrine axis and inflammatory factors in patients with irritable bowel syndrome （IBS）, with to provide a basis for the clinical diagnosis and treatment of IBS. Methods A total of 120 IBS patients admitted to the Second Central Hospital of Baoding City, Hebei Province from January 2023 to December 2024 were selected as the study group and classified into three subgroups based on their condition： diarrhea-predominant type （n=66）, constipation-predominant type （n=28）, and mixed type （n=26）. Another 120 healthy individuals who underwent physical examinations at the same hospital during the same period were selected as the control group. The gut microbiota, neuroendocrine axis functions, and inflammatory factors of the study group and the control group, as well as those of the patients with different subtypes of IBS, were compared. The correlations of the gut microbiota with the functions of the hypothalamic-pituitary-adrenal （HPA） axis, thyroid axis, and inflammatory markers were analyzed using the Pearson correlation analysis method. Results Compared with the control group, the levels of Bifidobacterium and Lactobacillus, serum free thyroxine （FT4）, and 8：00 adrenocorticotropic hormone （ACTH） in the study group were lower, while the levels of Enterobacter, Enterococcus, 24：00 serum ACTH, 16：00 serum cortisol （Cor）, serum total triiodothyronine （T3）, free triiodothyronine （FT3）, CC motif chemokine ligand 16 （CCL16）, interleukin-17A （IL-17A）, and absolute neutrophil count （NEUT） in whole blood were higher （P<0.05）. Compared with the diarrhea-predominant subtype, the levels of Bifidobacterium and Lactobacillus, serum FT4, and 8：00 ACTH in the constipation-predominant and mixed subtypes were lower, while the levels of Enterobacter, Enterococcus, 24：00 serum ACTH, 16：00 serum Cor, serum T3, FT3, CCL16, IL-17A, and NEUT in whole blood were higher （P<0.05）. Compared with the constipation-predominant subtype, the levels of Bifidobacterium and Lactobacillus, serum FT4, and 8：00 ACTH in the mixed subtype were lower, while the levels of Enterobacter, Enterococcus, 24：00 serum ACTH, 16：00 serum Cor, serum T3, FT3, CCL16, IL-17A, and NEUT in whole blood were higher （P<0.05）. The Pearson correlation analysis results showed that Bifidobacterium and Lactobacillus were positively correlated with 8：00 ACTH and FT4, and negatively correlated with 24：00 ACTH, 16：00 Cor, T3, FT3, NEUT, CCL16, and IL-17A （P<0.05）. Enterobacter and Enterococcus were negatively correlated with 8：00 ACTH and FT4, and positively correlated with 24：00 ACTH, 16：00 Cor, T3, FT3, NEUT, CCL16, and IL-17A （P<0.05）. Conclusion The dominant strains of gut microbiota in IBS patients change, and accompanied by circadian rhythm disorders of the HPA axis and thyroid axis. The indicator changes show an increasing trend in the diarrhea-predominant, constipation-predominant, and mixed types. Moreover, gut microbiota changes are closely related to the functions of the neuroendocrine axis and inflammatory factors.

关键词

肠易激综合征 / 肠道菌群 / 神经内分泌轴功能 / 炎症因子

Key words

irritable bowel syndrome / gut microbiota / neuroendocrine axis function / inflammatory factors