Research Projects

A. Background and Gaps: The apicomplexan protozoan parasite Cryptosporidium causes cryptosporidiosis, which is a leading cause of diarrhoea-related deaths not only in infants, but also in immunocompromised adults. Cryptosporidiosis is also associated with malnutrition and growth stunting in children, and there is currently neither a vaccine, nor an effective treatment exists for this disease. In a birth cohort study, 97% young children living in semiurban slums in Southern India were identified to be infected with Cryptosporidium. Malnutrition is a risk factor for cryptosporidiosis. Overnutrition is a form of malnutrition that can lead to obesity and associated metabolic dysfunction. Childhood obesity is an increasing global health concern and in India it is estimated that approximately 5 million children under age of 5 are either overweight or obese (NFHS-5). Although obesity-related inflammation and altered microbiota increases the risk of infections, their specific impact on the cryptosporidiosis in young children is unclear. Moreover, the impact of cryptosporidium infection on gut damage, inflammation and resulting metabolic dysfunction during obesity is yet to be defined. Therefore current proposal aims to define the following key questions using mouse model of obesity and cryptosporidiosis: B. Key questions & hypothesis: i. What is the influence of obesogenic-diet on immunoregulation of cryptosporidiosis? Rationale: Obesity compromises the gut immunity and immunodeficiency increases the risk of cryptosporidiosis. Hypothesis: Young mice fed high-fat diet (childhood obesity model) would be highly susceptible to cryptosporidiosis. ii. Does cryptosporidium infection increase gut permeability to cause early onset of fatty liver disease in obese mice? Rationale: Obesity is associated with increased gut permeability and endotoxemia. Cryptosporidium infection causes epithelial damage and inflammation. Hypothesis: Infected obese mice may have early onset of fatty liver disease due to exacerbated gut damage and leaky gut. iii. Can a dietary intervention with tryptophan metabolites prevent fatty liver disease development in infected obese mice? Rationale: My findings indicate that lack of indoles in diet compromises gut immunity and confers susceptibility to cryptosporidiosis. Obesity decreases tryptophan metabolising bacteria that produce indoles. Hypothesis: feeding the obese mice with natural or microbiota derived indoles may reduce infection and metabolic dysfunction. C. Importance of Proposed Research: Despite being major health concerns for children under 5, we know little about how early parasite infections affect obesity and metabolism. The objectives of this proposal will expand our understanding of cross talk between parasite infection and metabolic disorder, and shed light on development of prophylactic diet-based therapeutics.