Cross-modulation of pathogen-specific pathways enhances malnutrition during enteric co-infection with Giardia lamblia and enteroaggregative Escherichia coli

• DOI: 10.1371/journal.ppat.1006471
• Publication Date: 2017-07-27T13:39:51Z
• Authors: Luther A. Bartelt; David T. Bolick; Jordi Mayneris-Pe...; Glynis L. Kolling; Gregory L. Medlock; Edna I. Zaenker; Jeffery Donowitz; Rose Viguna Thoma...; Allison Rogala; Ian M. Carroll; Steven M. Singer; Jason Papin; Jonathan R. Swann; Richard L. Guerrant
• Keywords: Giardia lamblia; Giardia; Enteroaggregative Escherichia coli; Dysbiosis

Diverse enteropathogen exposures associate with childhood malnutrition. To elucidate mechanistic pathways whereby enteric microbes interact during malnutrition, we used protein deficiency in mice to develop a new model of co-enteropathogen enteropathy. Focusing on common enteropathogens malnourished children, Giardia lamblia and enteroaggregative Escherichia coli (EAEC), provide insights into intersecting pathogen-specific mechanisms that enhance We show for the first time intestinal microbiota permits persistent colonization simultaneously contributes growth impairment. Despite signals injury, such as IL1α, Giardia-infected lack pro-inflammatory responses, similar endemic pediatric infections. Rather, perturbs microbial host co-metabolites proteolysis impairment, whereas nicotinamide utilization adaptations correspond recovery increase. EAEC promotes inflammation markers myeloid cell activation. During co-infection, inflammatory signaling cellular recruitment responses are preserved together Giardia-mediated diminishment Conversely, extinguishes energy expenditure regulatory Giardia, metabolic appear exhausted. Integrating immunologic profiles co-pathogen infection working how cumulative diet-induced pathogen-triggered perturbations result an increasingly wasted host.