首页|期刊导航|同济大学学报(医学版)|造血干细胞移植患者肠道菌群改变与移植后营养指标及腹泻的相关性分析

造血干细胞移植患者肠道菌群改变与移植后营养指标及腹泻的相关性分析OA

Correlation between gut microbiota alterations and nutritional indicators and diarrhea in patients receiving hematopoietic stem cell transplantation

中文摘要英文摘要

目的 分析造血干细胞移植(hematopoietic stem cell transplantation,HSCT)患者移植前后肠道菌群动态变化与营养指标及腹泻的相关性.方法 纳入2023年7月-2024年12月在上海交通大学医学院附属仁济医院接受HSCT的血液系统疾病患者为研究对象.收集移植前1个月内及移植后14 d的粪便样本进行16S rRNA(ribosomal ribonucleic acid)基因测序.同时收集移植前后营养相关指标(体格测量指标、膳食摄入量及血生化指标)、移植后14 d内的大便次数及性状.腹泻的诊断标准为每天大便次数≥3次稀水样便.患者年龄、性别、原发疾病及移植种类根据病史获得.采用α-多样性及β-多样性来比较移植前后肠道菌群的差异,必要时对研究结果进行多重检验校正,错误发生率(false discovery rate,FDR)<0.05(Q<0.05)为差异有统计学意义.运用Spearman's rank相关性分析探讨肠道菌群与营养指标及腹泻的关系.结果 最终纳入63例患者(男性35例,女性28例),平均年龄53(46,60)岁.原发疾病分类为多发性骨髓瘤36例,非霍奇金淋巴瘤15例,其余血液系统疾病12例.患者移植后14 d内腹泻发生率为84.1%,平均腹泻持续天数为5(3,7)d.移植后体质量指数、腰围、小腿围、握力、膳食摄入量、白蛋白及前白蛋白呈下降趋势(P<0.05);白细胞计数、中性粒细胞绝对值和C反应蛋白呈上升趋势(P<0.05).移植后肠道菌群α-多样性(Sobs指数:移植前vs移植后为48.76±16.06 vs 29.98±19.53,Q<0.001;Shannon 指数:移植前 vs 移植后为 2.15±0.59 vs 1.22±0.83,Q<0.001;Simpson 指数:移植前vs移植后为0.23±0.16 vs 0.51±0.30,Q<0.001)及β-多样性存在显著差异(R2=0.11,P=0.001).种属水平分析结果显示丁酸梭菌(Clostridium.butyricum)与白细胞计数(r=0.34,P<0.01)、淋巴细胞绝对值(r=0.28,P=0.03)、中性粒细胞绝对值(r=0.28,P=0.03)和腹泻持续天数(r=0.26,P=0.04)呈正相关,与体质量指数(r=-0.3,P=0.02)呈负相关.多形拟杆菌(Bacteroides.thetaiotaomicron)与体质量指数(r=-0.27,P=0.04)及腹泻持续天数(r=-0.28,P=0.03)呈负相关;未分类瘤胃球菌 gnavus 群(uncultured_bacterium_g_[Ruminococcus]_gnavus_group)与握力(r=-0.29,P=0.03)呈负相关,差异均具有统计学意义.结论 HSCT患者肠道菌群发生显著变化,且与移植后营养指标及腹泻存在相关性.提示以菌群导向的营养干预(如特定益生菌补充)具有潜在的改善HSCT患者肠道功能和临床预后的应用前景.

Objective To analyze the dynamic changes in gut microbiota before and after hematopoietic stem cell transplantation(HSCT)and explore their correlation with nutritional indicators and diarrhea.Methods Patients who underwent HSCT at Renji Hospital,Shanghai Jiao Tong University School of Medicine,between July 2023 and December 2024 were enrolled.Fecal samples were collected within one month prior to transplantation and 14 days post-transplantation for 16S ribosomal ribonucleic acid(16s rRNA)gene sequencing.Nutritional indicators(anthropometric measurements,dietary intake,and blood biochemical markers)were recorded peri-transplantation.Stool frequency and consistency(assessed using the Bristol Stool Scale)were monitored in 14 days post-transplantation,with diarrhea defined as ≥3 loose or watery stools per day.The age,gender,and primary diagnosis,and transplantation type were obtained from medical records.Alpha and beta diversity analyses were used to compare gut microbiota changes.Multiple testing correction was applied to the research results when necessary,with a false discovery rate(FDR)<0.05(Q<0.05)considered statistically significant.Spearman correlation analysis was performed to assess the association between gut microbiota,nutritional indicators,and diarrhea.Results A total of 63 patients(35 males and 28 females)with a median age of 53 years[interquartile range(IQR):46 years,60 years]were included.The diagnoses included multiple myeloma(n=36),non-Hodgkin lymphoma(n=15),and other hematologic diseases(n=12).The incidence of early post-transplant diarrhea was 84.1%,with a median duration of 5 days(IQR:3,7 days).Post-transplant declines were observed in body mass index(BMI),waist circumference,calf circumference,handgrip strength,dietary intake,albumin,and prealbumin(all P<0.05),while white blood cell count,absolute neutrophil count,and C-reactive protein levels increased(all P<0.05).Significant reductions in alpha diversity indices(pre-vs.post-HSCT:Sobs index:48.76±16.06 vs.29.98±19.53;Shannon index:2.15±0.59 vs 1.22±0.83;Simpson index:0.23±0.16 vs 0.51±0.30;all Q<0.001)were observed post-transplantation,along with altered beta diversity(R2=0.11,P=0.001).Clostridium butyricum positively correlated with white blood cell count(r=0.34,P<0.01),absolute lymphocyte count(r=0.28,P=0.03),absolute neutrophil count(r=0.28,P=0.03),and diarrhea duration(r=0.26,P=0.04),but negatively correlated with BMI(r=-0.30,P=0.02).Bacteroides thetaiotaomicron showed negative correlations with BMI(r=-0.27,P=0.04)and diarrhea duration(r=-0.28,P=0.03),while uncultured_bacterium_g_[Ruminococcus]_gnavus_group was negatively associated with handgrip strength(r=-0.29,P=0.03).Conclusion HSCT significantly alters gut microbiota composition,which correlates with nutritional indicators and diarrhea during early post-transplantation.These findings suggest that microbiota-guided nutritional interventions,such as specific probiotics supplementation,have potential to improve gut function and clinical outcomes in HSCT patients.

唐墨莲;宋安琪;张旻玥;沈莉菁;徐仁应

华北理工大学公共卫生学院,河北唐山 063210上海交通大学医学院附属仁济医院临床营养科,上海 200127上海交通大学医学院附属仁济医院血液科,上海 200127上海交通大学医学院附属仁济医院血液科,上海 200127华北理工大学公共卫生学院,河北唐山 063210||上海交通大学医学院附属仁济医院临床营养科,上海 200127

医药卫生

肠道菌群造血干细胞移植血液系统疾病

gut microbiotahematopoietic stem cell transplantationhematologic disease

《同济大学学报(医学版)》 2026 (2)

214-223,10

中国食品科学技术学会食品科技基金-雅培食品营养与安全专项科研基金(2021-M05)

10.12289/j.issn.2097-4345.25194

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