JID：肠粘膜通透性高的婴儿或更易经由母乳喂养途径感染HIV

在母亲感染HIV-1且经由母乳喂养的婴儿中，尽管他们在数月内摄取了含有HIV-1的母乳，其中他们中的大部分都不会感染HIV。小肠通透性的增加可能有利于HIV在母乳喂养中的传播，而胃肠道的感染、营养不良和人工喂养都会影响肠粘膜屏障的成熟，增加肠道的通透性。这也许可以解释混合喂养的HIV感染风险比纯母乳喂养要高。一项研究显示，3月龄时，非洲婴儿的肠通透性比欧洲婴儿高，而12月龄时，非洲婴儿的肠通透性是欧洲婴儿的5倍。然而，传统评估肠通透性的方法是通过对碳水化合物的吸收来进行的，而这在婴儿中是难以实行的。

由于肠屏障的破坏，导致细菌或内毒素通过肠粘膜从肠腔内转移到体循环中，这就是微生物易位，可通过测量血浆中LPS的水平来进行量化。因而血浆LPS水平的升高预示着肠粘膜完整性的破坏，这可在胃肠道微创手术、移植物抗宿主反应疾病、炎症性肠疾病和HIV感染中发生。为了验证肠道微生物易位与母乳喂养所致HIV感染风险的升高有关，来自亚特兰大疾病控制和预防中心的Athena P. Kourtis等进行了一项研究，研究结果在线发表在Journal of Infectious Diseases上。研究发现，肠粘膜不完整可能有利于HIV在母乳喂养中的传播。

研究者对来自BAN研究（Breastfeeding，Antiretrovirals and Nutrition Study）的HIV接触感染和未感染婴儿的一系列样本进行研究，测量了血浆LPS水平和免疫活化标志物。

结果显示，婴儿的血浆LPS水平在24周断奶后有所增加。采用磺胺甲基异恶唑预防与血浆LPS水平的升高有关（p=0.004）。此外，HIV感染婴儿的血浆LPS比未感染婴儿要高。感染前血浆LPS水平是婴儿通过母乳喂养获得HIV感染的一个重要的预测因子(HR=1.6)，也预示着婴儿寿命更短（p=0.02）。

研究发现，肠屏障完整性的破坏可能导致婴儿通过母乳喂养获得HIV。而断奶和使用抗生素预防与微生物易位水平的升高有关，可能有利于HIV通过肠进入体循环。因此，增强婴儿肠粘膜完整性的辅助方法可能有助于减少HIV在母乳喂养中的传播。

Role of Intestinal Mucosal Integrity in HIV Transmission to Infants Through Breast-feeding: The BAN Study.
Abstract
Background. Increased intestinal permeability may be one of the mechanisms of transmission of human immunodeficiency virus (HIV) to infants through breast-feeding. Intestinal permeability correlates with microbial translocation, which can be measured through quantification of bacterial lipopolysaccharide (LPS).Methods. We evaluated levels of plasma LPS (by the Limulus amebocyte lysate assay) and immune activation markers in serial specimens from infants exposed to but uninfected with HIV and infants infected with HIV from the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study.Results. Plasma LPS levels increased after infants in the BAN study were weaned from the breast, at 24 weeks of age. Cotrimoxazole prophylaxis was associated with higher plasma LPS levels (P = .004). Infants with HIV infection had higher LPS levels, compared with uninfected infants (P = .004). Higher preinfection plasma LPS levels were a significant predictor of infant HIV infection through breast-feeding (hazard ratio = 1.60 for every unit increase in plasma LPS level; P = .01) and of lower infant length-for-age z scores (P = .02).Conclusions. These findings suggest that disruption in intestinal integrity is a mechanism of HIV transmission to infants through breast-feeding. Weaning from breast milk and use of antibiotic prophylaxis was associated with increased levels of microbial translocation, which could facilitate HIV entry through the intestine. Complementary approaches to enhance intestinal mucosal integrity in the infant may further reduce breast-feeding transmission of HIV.