Table 3_Association of Escherichia coli pathotypes with fecal markers of enteropathy and nutritional status among underweight adults in Bangladesh.xlsx

IntroductionEnvironmental enteric dysfunction (EED), a subclinical intestinal disorder, is characterized by chronic fecal-oral exposure to entero-pathogens and could be diagnosed by measuring non-invasive biomarkers. Escherichia coli is the one of the key bacterial enteric pathogens that drives EED, but there is a lack of information on the E. coli pathotypes in relation to the biomarkers of EED in malnourished adults. Here, we intended to measure the possible association of these pathotypes with EED biomarkers and nutritional status of adults residing in a slum in Bangladesh.
MethodFecal samples were collected from 524 malnourished adults (BMI ≤18.5 kg/m2) living in a slum-setting in Dhaka from March 2016 to September 2019 and analyzed by TaqMan Array Card assays to evaluate the presence of E. coli pathotypes and other entero-pathogens. The multivariable linear regression model was used to assess the association.
ResultsIn these malnourished adults, the most prevalent pathotype of E. coli was EAEC (61.7%) and the least prevalent was STEC (6.7%). The prevalence of atypical EPEC, ETEC and Shigella/EIEC were 52%, 48.9% and 45.1% respectively. The infection with atypical EPEC had significant positive association with levels of Myeloperoxidase (b = 0.38; 95% CI = 0.11, 0.65; p-value = 0.006). Similarly, a significantly higher concentration of alpha-1-antitrypsin (b = 0.13; 95% CI = 0.03, 0.22; p-value = 0.011) was found in the STEC-infected adults. However, no notable association was found between the E. coli pathotypes and nutritional status of these adult participants. Moreover, Plesiomonas infected adults were more likely to be infected with EAEC (p-value = 0.017), ETEC (p-value <0.001) and STEC (pvalue = 0.002). Significant coinfection was also detected among the pathotypes and other entero-pathogens such as Giardia, Ascaris, Campylobacter, Salmonella, Enterocytozoon bieneusi, and Adenovirus.
DiscussionThe study results imply that there is an influence of particular E. coli pathotypes (EPEC and STEC) on intestinal inflammation and gut permeability of the malnourished Bangladeshi adults, but no association with nutritional status is found. Potential pathogenicity of the E. coli pathotypes is also observed when co-infection with other pathogens exists in these adults.

引言
环境性肠功能障碍（Environmental enteric dysfunction, EED）是一种亚临床肠道疾病，其特征为慢性粪口暴露于肠道病原菌，可通过检测无创生物标志物进行诊断。大肠埃希菌（Escherichia coli, E. coli）是介导EED发生的关键肠道细菌病原菌之一，但目前针对营养不良成人中E. coli致病型与EED生物标志物之间的关联仍缺乏相关研究数据。本研究旨在探究居住在孟加拉国贫民窟的成人中，此类致病型与EED生物标志物及营养状况的潜在关联。

方法
2016年3月至2019年9月，研究团队从孟加拉国达卡贫民窟地区的524名营养不良成人（体重指数≤18.5 kg/m²，Body Mass Index, BMI）中收集粪便样本，采用TaqMan阵列卡（TaqMan Array Card）检测法分析样本中E. coli致病型及其他肠道病原菌的存在情况。本研究使用多变量线性回归模型评估二者的相关性。

结果
在本次研究纳入的营养不良成人中，检出率最高的E. coli致病型为肠聚集性大肠埃希菌（Enteroaggregative Escherichia coli, EAEC，61.7%），最低的为产志贺毒素大肠埃希菌（Shiga toxin-producing Escherichia coli, STEC，6.7%）。非典型肠致病性大肠埃希菌（Enteropathogenic Escherichia coli, atypical EPEC）、产肠毒素大肠埃希菌（Enterotoxigenic Escherichia coli, ETEC）以及志贺菌/肠侵袭性大肠埃希菌（Shigella/Enteroinvasive Escherichia coli, Shigella/EIEC）的检出率分别为52%、48.9%与45.1%。感染非典型EPEC与髓过氧化物酶（Myeloperoxidase）水平呈显著正相关（b=0.38；95%置信区间CI=0.11, 0.65；p值=0.006）。同样，STEC感染成人的α-1-抗胰蛋白酶（alpha-1-antitrypsin）浓度显著更高（b=0.13；95%置信区间CI=0.03, 0.22；p值=0.011）。然而，未发现E. coli致病型与本次研究的成人参与者营养状况存在显著关联。此外，邻单胞菌（Plesiomonas）感染者更易合并感染EAEC（p值=0.017）、ETEC（p值<0.001）及STEC（p值=0.002）。研究还在E. coli致病型与其他肠道病原菌（如蓝氏贾第鞭毛虫Giardia、蛔虫Ascaris、弯曲杆菌Campylobacter、沙门氏菌Salmonella、比氏肠胞虫Enterocytozoon bieneusi以及腺病毒Adenovirus）之间检测到显著的共感染现象。

讨论
本研究结果表明，特定E. coli致病型（肠致病性大肠埃希菌EPEC与产志贺毒素大肠埃希菌STEC）可对孟加拉国营养不良成人的肠道炎症及肠道通透性产生影响，但未发现其与营养状况存在相关性。当此类成人合并感染其他病原菌时，也可观察到E. coli致病型具备潜在致病性。