Probiotics for Infectious Diarrhea in Children in South India

描述（由申请人提供）：根据PAR-07-216（印度-美国妇幼保健计划）提交的这项合作研究的总体目标是调查胃肠道益生菌的调节作用是否促进肠道功能的恢复，并增强南印度隐孢子虫或轮状病毒感染儿童的免疫反应。轮状病毒和隐孢子虫是印度南部儿童胃肠炎最重要的病毒和寄生虫。这两种感染都可导致幼儿严重的脱水性胃肠炎，并可能由于肠道损伤而对营养状况产生长期有害影响。大多数传染性胃肠炎发作通过补液解决，但口服补液仍未得到充分利用，部分原因是对排便频率和疾病持续时间缺乏影响。已知益生菌有益调节几种宿主功能，其中最重要的是免疫反应和肠道屏障完整性。基于鼠李糖乳杆菌GG （Lactobacillus rhamnosus GG， LGG）治疗多种腹泻疾病的疗效，以及益生菌调节免疫反应和增强肠上皮屏障功能的文献记载，我们计划对LGG与安慰剂在缓解症状和恢复肠道功能，特别是通透性和碳水化合物吸收方面的作用进行机制研究。患有轮状病毒或隐孢子虫腹泻且未发现其他肠道感染的儿童。我们还将研究补充4周LGG对这些感染免疫反应的影响。这项研究是朝着提供一种辅助疗法来治疗急性腹泻疾病及其长期不良后果的目标迈出的第一步。LGG有可能成为处理这些具有重大公共卫生重要性的病原体的一种容易获得、具有成本效益的方法。在发展中国家，腹泻造成大量死亡和疾病，而病原体通常是通过食物、水和不良卫生条件获得的。在这些研究中，我们将研究使用益生菌或“好”细菌治疗印度南部两种最常见病原体引起的腹泻儿童的效果，以确定它们是否有助于预防或修复肠壁损伤，以及它们是否有助于促进免疫反应，以防止进一步感染。这些研究对于了解益生菌是否以及如何保护和治愈肠道非常重要。

DESCRIPTION (provided by applicant): The overall goal of this collaborative study submitted in response to PAR-07-216 (Indo- US Program for Maternal and Child Health) is to investigate whether the modulatory effects of probiotics in the gastrointestinal tract promote restoration of intestinal function and enhance the immune response in children with cryptosporidial or rotaviral infections in South India. Rotavirus and Cryptosporidium spp. are the most important viral and parasitic causes of gastroenteritis in children in south India. Both infections can lead to severe dehydrating gastroenteritis in young children as well as long term deleterious effects on nutritional status, likely due to intestinal damage. Most episodes of infectious gastroenteritis resolve with rehydration, but oral rehydration remains under-utilized, in part due to the lack of effect on frequency of bowel movements and duration of illness. Probiotics are known to beneficially modulate several host functions, the most important of which are immune responses and intestinal barrier integrity. Based on the established efficacy of Lactobacillus rhamnosus GG (LGG) for the treatment of a variety of diarrheal diseases and the documented modulation of immune responses and strengthening of intestinal epithelial barrier function by probiotics, we plan to conduct mechanistic studies on the effect of LGG vs. placebo in the resolution of symptoms and restoration of intestinal function, particularly permeability and carbohydrate absorption, in children with either rotaviral or cryptosporidial diarrhea and no other detected enteric infection. We will also study the effects of four weeks of supplementation with LGG on immune response to these infections. This study is a first step towards the goal of providing an understanding of a complementary therapy to treat acute diarrheal illness and its long term adverse consequences. LGG has the potential to be an easily accessible, cost effective approach to these pathogens of major public health importance. /Relevance Diarrhea causes significant death and disease in developing countries and the agents are usually acquired through food, water and poor hygiene. In these studies, we will study the effect of treatment of children with diarrhea due to the two most common pathogens in southern India, with probiotics or "good" bacteria in order to determine whether they help in preventing or repairing damage to the intestinal wall and whether they help in promoting an immune response that will protect from further infections. These studies are important to help understand whether and how probiotics work in protecting and healing the intestine.