Given the global burden of diarrheal diseases1, it is important to understand how members of the gut microbiota affect the risk for, course of, and recovery from disease in children and adults. The acute, voluminous diarrhea caused by Vibrio cholerae represents a dramatic example of enteropathogen invasion and gut microbial community disruption. We have conducted a detailed time-series metagenomic study of fecal microbiota collected during the acute diarrheal and recovery phases of cholera in a cohort of Bangladeshi adults living in an area with a high burden of disease2. We find that recovery is characterized by a pattern of accumulation of bacterial taxa that shows similarities to the pattern of assembly/maturation of the gut microbiota in healthy Bangladeshi children3. To define underlying mechanisms, we introduced into gnotobiotic mice an artificial community that was composed of human gut bacterial species that directly correlate with recovery from cholera in adults and are indicative of normal microbiota maturation in healthy Bangladeshi children3. One of the species, Ruminococcus obeum, exhibited consistent increases in its relative abundance upon V. cholerae infection of the mice. Follow-up analyses, including mono- and co-colonization studies, established that R. obeum restricts V. cholerae colonization, that R. obeum luxS [autoinducer-2 (AI-2) synthase] expression and AI-2 production increase significantly with V. cholerae invasion, and that R. obeum AI-2 causes quorum-sensing mediated repression of several V. cholerae colonization factors. Co-colonization with V. cholerae mutants disclosed that R. obeum AI-2 reduces Vibrio colonization/pathogenicity through a novel pathway that does not depend on the V. cholerae AI-2 sensor, LuxP. The approach described can be used to mine the gut microbiota of Bangladeshi or other populations for members that use autoinducers and/or other mechanisms to limit colonization with V. cholerae, or conceivably other enteropathogens.

Undernutrition is the single largest contributor to the global burden of disease and can be addressed through a number of highly efficacious interventions. Undernutrition generally has not received commensurate attention in policy agendas at global and national levels, however, and implementing these efficacious interventions at a national scale has proven difficult. This paper reports on the findings from studies in Bangladesh, Bolivia, Guatemala, Peru and Vietnam which sought to identify the challenges in the policy process and ways to overcome them, notably with respect to commitment, agenda setting, policy formulation and implementation. Data were collected through participant observation, documents and interviews. Data collection, analysis and synthesis were guided by published conceptual frameworks for understanding malnutrition, commitment, agenda setting and implementation capacities. The experiences in these countries provide several insights for future efforts: (a) high-level political attention to nutrition can be generated in a number of ways, but the generation of political commitment and system commitment requires sustained efforts from policy entrepreneurs and champions; (b) mid-level actors from ministries and external partners had great difficulty translating political windows of opportunity for nutrition into concrete operational plans, due to capacity constraints, differing professional views of undernutrition and disagreements over interventions, ownership, roles and responsibilities; and (c) the pace and quality of implementation was severely constrained in most cases by weaknesses in human and organizational capacities from national to frontline levels. These findings deepen our understanding of the factors that can influence commitment, agenda setting, policy formulation and implementation. They also confirm and extend upon the growing recognition that the heavy investment to identify efficacious nutrition interventions is unlikely to reduce the burden of undernutrition unless or until these systemic capacity constraints are addressed, with an emphasis initially on strategic and management capacities.