Biomarkers of Environmental Enteropathy, Inflammation, Stunting, and Impaired Growth in Children in Northeast Brazil

被引：160

作者：

Guerrant, Richard L. ^{[1
,2
]}

Leite, Alvaro M. ^{[3
]}

Pinkerton, Relana ^{[1
,2
]}

Medeiros, Pedro H. Q. S. ^{[3
]}

Cavalcante, Paloma A. ^{[3
]}

DeBoer, Mark ^{[1
,2
]}

Kosek, Margaret ^{[10
]}

Duggan, Christopher ^{[4
]}

Gewirtz, Andrew ^{[5
]}

Kagan, Jonathan C. ^{[4
]}

Gauthier, Anna E. ^{[4
]}

Swann, Jonathan ^{[8
]}

Mayneris-Perxachs, Jordi ^{[8
]}

Bolick, David T. ^{[2
]}

Maier, Elizabeth A. ^{[9
]}

Guedes, Marjorie M. ^{[9
]}

Moore, Sean R. ^{[9
]}

Petri, William A. ^{[1
,2
]}

Havt, Alexandre ^{[3
]}

Lima, Ila F. ^{[3
]}

Gondim Prata, Mara de Moura ^{[3
]}

Michaleckyj, Josyf C. ^{[1
,2
]}

Scharf, Rebecca J. ^{[1
,2
]}

Sturgeon, Craig ^{[6
,7
]}

Fasano, Alessio ^{[6
,7
]}

Lima, Aldo A. M. ^{[3
]}

机构：

[1] Univ Virginia, Sch Med, Dept Med, Dept Pediat,Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA

[2] Univ Virginia, Sch Med, Ctr Global Hlth, Charlottesville, VA 22908 USA

[3] Univ Fed Ceara, Clin Res Unit, Fortaleza, Ceara, Brazil

[4] Harvard Univ, Boston Childrens Hosp, Div Gastroenterol, Boston, MA 02115 USA

[5] Georgia State Univ, Inst Biomed Sci, Ctr Inflammat Immun & Infect, Atlanta, GA 30303 USA

[6] Harvard Univ, Massachusetts Gen Hosp Children, Mucosal Immunol & Biol Res Ctr, Boston, MA 02115 USA

[7] Harvard Univ, Massachusetts Gen Hosp Children, Div Pediat Gastroenterol & Nutr, Boston, MA 02115 USA

[8] Imperial Coll, London, England

[9] Cincinnati Childrens Hosp, Cincinnati, OH USA

[10] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA

来源：

PLOS ONE | 2016年 / 11卷 / 09期

基金：

比尔及梅琳达.盖茨基金会; 美国国家卫生研究院;

关键词：

EARLY-CHILDHOOD DIARRHEA; CATCH-UP GROWTH; FAT DISTRIBUTION; INTESTINAL INFLAMMATION; PERSISTENT DIARRHEA; GENDER-DIFFERENCES; AFRICAN-AMERICAN; BARRIER FUNCTION; LINEAR GROWTH; BODY-FAT;

D O I：

10.1371/journal.pone.0158772

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：20

共 69 条

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