Guerrant Richard L, Leite Alvaro M, Pinkerton Relana, Medeiros Pedro H Q S, Cavalcante Paloma A, DeBoer Mark, Kosek Margaret, Duggan Christopher, Gewirtz Andrew, Kagan Jonathan C, Gauthier Anna E, Swann Jonathan, Mayneris-Perxachs Jordi, Bolick David T, Maier Elizabeth A, Guedes Marjorie M, Moore Sean R, Petri William A, Havt Alexandre, Lima Ila F, Prata Mara de Moura Gondim, Michaleckyj Josyf C, Scharf Rebecca J, Sturgeon Craig, Fasano Alessio, Lima Aldo A M
University of Virginia School of Medicine (Division of Infectious Diseases and International Health, Department of Medicine, Department of Pediatrics and Center for Global Health), Charlottesville, VA, United States of America.
Clinical Research Unit, Federal University of Ceara, Fortaleza, Brazil.
PLoS One. 2016 Sep 30;11(9):e0158772. doi: 10.1371/journal.pone.0158772. eCollection 2016.
Critical to the design and assessment of interventions for enteropathy and its developmental consequences in children living in impoverished conditions are non-invasive biomarkers that can detect intestinal damage and predict its effects on growth and development. We therefore assessed fecal, urinary and systemic biomarkers of enteropathy and growth predictors in 375 6-26 month-old children with varying degrees of malnutrition (stunting or wasting) in Northeast Brazil. 301 of these children returned for followup anthropometry after 2-6m. Biomarkers that correlated with stunting included plasma IgA anti-LPS and anti-FliC, zonulin (if >12m old), and intestinal FABP (I-FABP, suggesting prior barrier disruption); and with citrulline, tryptophan and with lower serum amyloid A (SAA) (suggesting impaired defenses). In contrast, subsequent growth was predicted in those with higher fecal MPO or A1AT and also by higher L/M, plasma LPS, I-FABP and SAA (showing intestinal barrier disruption and inflammation). Better growth was predicted in girls with higher plasma citrulline and in boys with higher plasma tryptophan. Interactions were also seen with fecal MPO and neopterin in predicting subsequent growth impairment. Biomarkers clustered into markers of 1) functional intestinal barrier disruption and translocation, 2) structural intestinal barrier disruption and inflammation and 3) systemic inflammation. Principle components pathway analyses also showed that L/M with %L, I-FABP and MPO associate with impaired growth, while also (like MPO) associating with a systemic inflammation cluster of kynurenine, LBP, sCD14, SAA and K/T. Systemic evidence of LPS translocation associated with stunting, while markers of barrier disruption or repair (A1AT and Reg1 with low zonulin) associated with fecal MPO and neopterin. We conclude that key noninvasive biomarkers of intestinal barrier disruption, LPS translocation and of intestinal and systemic inflammation can help elucidate how we recognize, understand, and assess effective interventions for enteropathy and its growth and developmental consequences in children in impoverished settings.
对于生活在贫困环境中的儿童肠病及其发育后果的干预措施设计和评估而言，关键在于能够检测肠道损伤并预测其对生长发育影响的非侵入性生物标志物。因此，我们评估了巴西东北部375名6至26个月大、患有不同程度营养不良（发育迟缓或消瘦）儿童的肠病粪便、尿液和全身生物标志物以及生长预测指标。其中301名儿童在2至6个月后返回进行随访人体测量。与发育迟缓相关的生物标志物包括血浆抗LPS IgA和抗FliC、zonulin（如果年龄大于12个月）以及肠道脂肪酸结合蛋白（I-FABP，提示先前屏障破坏）；与瓜氨酸、色氨酸以及较低血清淀粉样蛋白A（SAA）相关（提示防御功能受损）。相比之下，粪便MPO或A1AT较高者以及L/M、血浆LPS、I-FABP和SAA较高者（显示肠道屏障破坏和炎症）预测随后生长情况较好。血浆瓜氨酸较高的女孩和血浆色氨酸较高的男孩预测生长情况较好。在预测随后生长障碍方面，还观察到粪便MPO和新蝶呤之间的相互作用。生物标志物可分为1）功能性肠道屏障破坏和易位标志物、2）结构性肠道屏障破坏和炎症标志物以及3）全身炎症标志物。主成分通路分析还表明，L/M与%L、I-FABP和MPO与生长受损相关，同时也（如MPO）与犬尿氨酸、LBP、sCD14、SAA和K/T的全身炎症簇相关。LPS易位的全身证据与发育迟缓相关，而屏障破坏或修复标志物（低zonulin时的A1AT和Reg1）与粪便MPO和新蝶呤相关。我们得出结论，肠道屏障破坏、LPS易位以及肠道和全身炎症的关键非侵入性生物标志物有助于阐明我们如何识别、理解和评估针对贫困环境中儿童肠病及其生长发育后果的有效干预措施。
Zotero 插件
