1 Department of Pediatrics, Washington University at Saint Louis, St. Louis, MO 63110, USA.
2 School of Public Health and Family Medicine, University of Malawi, Blantyre 3, Malawi.
Exp Biol Med (Maywood). 2018 May;243(8):677-683. doi: 10.1177/1535370218768508. Epub 2018 Mar 29.
The dual sugar absorption test, specifically the lactulose:mannitol test, is used to assess gut health. Lactulose absorption is said to represent gut damage and mannitol absorption is used as a measure of normal small bowel function and serves as normalizing factor for lactulose. A underappreciated limitation of this common understanding of the lactulose:mannitol test is that mannitol is not absorbed to any substantial extent by a transcellular process. Additionally, this interpretation of lactulose:mannitol is not consistent with current understanding of paracellular pathways, where three pathway types exist: pore, leak, and unrestricted. Pore and leak pathways are regulated biological constructions of the small bowel barrier, and unrestricted pathways represent micropathological damage. We analyzed 2334 lactulose:mannitol measurements rigorously collected from 622 young rural Malawian children at high risk for poor gut health in light of the pathway model. An alternative method of normalizing for gut length utilizing autopsy data is described. In our population, absorbed lactulose and mannitol are strongly correlated, r = 0.68 P <0.0001, suggesting lactulose and mannitol are traversing the gut barrier via the same pathways. Considering measurements where pore pathways predominate, mannitol flux is about 14 times that of lactulose. As more leak pathways are present, this differential flux mannitol:lactulose falls to 8:1 and when increased numbers of unrestricted pathways are present, the differential flux of mannitol:lactulose is 6:1. There was no substantial correlation between the lactulose:mannitol and linear growth. Given that mannitol will always pass through a given pathway at a rate at least equal to that of lactulose, and lactulose absorption is a composite measure of flux through both physiologic and pathologic pathways, we question the utility of the lactulose:mannitol test. We suggest using lactulose alone is as informative as lactulose:mannitol in a sugar absorption testing in subclinical gut inflammation. Impact statement Our work integrates the standard interpretation of the lactulose:mannitol test (L:M), with mechanistic insight of intestinal permeability. There are three paracellular pathways in the gut epithelium; pore, leak, and unrestricted. Using thousands of L:M measurements from rural Malawian children at risk for increased intestinal permeability, we predict the differential flux of L and M through the pathways. Our findings challenge the traditional notions that little L is absorbed through a normal epithelial barrier and that M is a normalizing factor for L. Our observations are consistent with pore pathways allowing only M to pass. And that substantial amounts of L and M pass through leak pathways which are normal, regulated, cell-junctional adaptations. So M is a composite measure of all pathways, and L is not a measure solely of pathologic gut damage. Using L alone as a probe will yield more information about gut health than L:M.
双糖吸收试验,特别是乳果糖:甘露醇试验,用于评估肠道健康。乳果糖的吸收被认为代表肠道损伤,而甘露醇的吸收被用作正常小肠功能的衡量标准,并作为乳果糖的归一化因子。这种对乳果糖:甘露醇试验的常见理解的一个被低估的局限性是,甘露醇不会通过细胞间过程被吸收到任何实质性程度。此外,这种对乳果糖:甘露醇的解释与当前对旁细胞途径的理解不一致,旁细胞途径存在三种途径类型:孔、渗漏和不受限制。孔和渗漏途径是小肠屏障的调节生物结构,而不受限制的途径代表微观病理损伤。我们根据途径模型,对从 622 名高危不良肠道健康的马拉维农村儿童中严格收集的 2334 次乳果糖:甘露醇测量值进行了分析。描述了一种利用尸检数据归一化肠道长度的替代方法。在我们的人群中,吸收的乳果糖和甘露醇呈强相关,r=0.68,P<0.0001,表明乳果糖和甘露醇通过相同的途径穿过肠道屏障。考虑到以孔途径为主的测量值,甘露醇通量约为乳果糖的 14 倍。随着渗漏途径的增加,甘露醇:乳果糖的这种差异通量下降到 8:1,当不受限制的途径数量增加时,甘露醇:乳果糖的差异通量为 6:1。乳果糖:甘露醇与线性生长之间没有实质性的相关性。鉴于甘露醇将始终以至少等于乳果糖的速率通过给定途径,并且乳果糖的吸收是通过生理和病理途径的通量的综合衡量标准,我们对乳果糖:甘露醇试验的实用性提出质疑。我们建议在亚临床肠道炎症中,使用乳果糖单独进行糖吸收测试与乳果糖:甘露醇测试一样具有信息性。肠道上皮中有三种旁细胞途径;孔、渗漏和不受限制。我们使用来自高危肠道通透性增加的马拉维农村儿童的数千次乳果糖:甘露醇测量值,预测 L 和 M 通过途径的差异通量。我们的发现挑战了传统观念,即少量的 L 通过正常的上皮屏障被吸收,而 M 是 L 的归一化因子。我们的观察结果与仅允许 M 通过孔途径一致。并且大量的 L 和 M 通过正常、调节、细胞连接的适应性渗漏途径通过。因此,M 是所有途径的综合衡量标准,而 L 不仅仅是肠道损伤的衡量标准。单独使用 L 作为探针将比 L:M 提供更多关于肠道健康的信息。
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