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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
5R03HD057736-02
Application #
7599643
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Raiten, Daniel J
Project Start
2008-04-01
Project End
2011-03-31
Budget Start
2009-04-01
Budget End
2011-03-31
Support Year
2
Fiscal Year
2009
Total Cost
$80,500
Indirect Cost
Name
Tufts University
Department
Type
DUNS #
079532263
City
Boston
State
MA
Country
United States
Zip Code
02111