Holtz Lori R, Hoffmann Julie, Linneman Laura, He Mai, Smyrk Thomas C, Liu Ta-Chiang, Shaikh Nurmohammad, Rodriguez Cynthia, Dyer Roy B, Singh Ravinder J, Faubion William A
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States.
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, United States.
Front Pediatr. 2022 Apr 7;10:874116. doi: 10.3389/fped.2022.874116. eCollection 2022.
We sought to correlate two different measures of gut permeability [lactulose:mannitol (L:M) and lactulose:rhamnose (L:R)] to the severity of duodenal histopathology in children with and without elevated antibodies to tissue transglutaminase (tTG). A secondary objective was to correlate gut permeability with celiac disease (CD) serology and indices of inflammation and bacterial product translocation.
We prospectively randomized children undergoing endoscopy with abnormal ( = 54) and normal ( = 10) concentrations of circulating antibodies to tTG, to either L:M or L:R. Biopsies underwent modified Marsh scoring to measure mucosal injury. Circulating anticore lipopolysaccharide (LPS) IgG, α-1 acid glycoprotein, LPS-binding protein, and C-reactive protein concentrations were measured by enzyme immunoassays.
Of the 54 cases with positive celiac serology, 31 and 69% had modified Marsh 0/1 scores or ≥3a, respectively. Circulating tTG IgA correlated with the modified Marsh score ( = 0.03). L:R, but not L:M or percent L excreted, differed according to modified Marsh scores ( = 0.01). There was no significant association between any systemic marker of inflammation or gut injury, and modified Marsh scores. Concerningly, most participants had evidence of urinary M before the challenge sugar was administered.
L:R, but not L:M, is associated with modified Marsh scores in children undergoing small bowel biopsy for suspected CD. Despite increased intestinal permeability, we see scant evidence of systemic exposure to gut microbes in these children. Gut permeability testing with L:R may predict which patients with abnormal celiac serology will have biopsy evidence for celiac disease and reduce the proportion of such patients undergoing endoscopy whose Marsh scores are ≤1. M should not be used as a monosaccharide for permeability testing in children.
我们试图将两种不同的肠道通透性测量指标[乳果糖：甘露醇（L:M）和乳果糖：鼠李糖（L:R）]与有或没有组织转谷氨酰胺酶（tTG）抗体升高的儿童十二指肠组织病理学严重程度相关联。次要目标是将肠道通透性与乳糜泻（CD）血清学、炎症指标和细菌产物易位相关联。
我们将接受内镜检查且循环中tTG抗体浓度异常（n = 54）和正常（n = 10）的儿童前瞻性随机分为L:M组或L:R组。活检标本进行改良马什评分以测量黏膜损伤。通过酶免疫测定法测量循环中的抗核心脂多糖（LPS）IgG、α-1酸性糖蛋白、LPS结合蛋白和C反应蛋白浓度。
在54例乳糜泻血清学阳性的病例中，分别有31%和69%的病例改良马什评分为0/1或≥3a。循环中的tTG IgA与改良马什评分相关（r = 0.03）。L:R根据改良马什评分有所不同（p = 0.01），而L:M或排泄的L百分比则不然。任何炎症或肠道损伤的全身标志物与改良马什评分之间均无显著关联。令人担忧的是，大多数参与者在给予激发糖之前就有尿中甘露醇的证据。
在因疑似CD接受小肠活检的儿童中，L:R而非L:M与改良马什评分相关。尽管肠道通透性增加，但在这些儿童中我们几乎没有发现全身暴露于肠道微生物的证据。用L:R进行肠道通透性测试可能预测哪些乳糜泻血清学异常的患者将有乳糜泻的活检证据，并减少那些马什评分≤1的接受内镜检查的此类患者的比例。在儿童中，甘露醇不应作为通透性测试的单糖使用。
