Lumen tysons sitemap1/26/2024 ![]() ![]() More importantly, the interpretation of these observations is complicated by the lack of comparison to samples obtained from asymptomatic children living under the same conditions. While this study reported an association between growth faltering and damage to the upper small intestine, the involvement of other gut sites remains unknown. One study reported increased gut permeability and inflammation markers in duodenal biopsies obtained from Gambian infants with growth faltering compared to those obtained from healthy children living in the United Kingdom 9. In addition, few studies have investigated diarrheal disease-induced damage within the gut itself. Additional studies are needed to determine the role of these newly identified pathogens in the cycle of diarrheal disease, malnutrition, and growth faltering. More recent studies have begun to identify a set of non-traditional pathogens, especially in the genus Campylobacter, that are missed by clinical tests but highly abundant in developing countries 24, 25, 26. ![]() This pattern is likely a combination of high pathogen burden in the absence of symptoms 19, 20, 21 and the use of clinical tests that limit detection of novel pathogens not routinely detected 22, 23. Specifically, multiple large-scale international studies have found that less than 50% of diarrheal cases can be attributed to a specific pathogen 19, 20. Moreover, unknown and emerging etiological agents are thought to play an underappreciated role in childhood diarrheal disease and growth faltering. These subclinical infections are believed to perpetuate intestinal damage and restrict healthy growth 18. Indeed, growth faltering children in developing countries have been shown to have a significant enteric pathogen burden without acute disease 14, 16, 17. This cycle can occur even in the absence of overt diarrhea 14, 15. Specifically, diarrhea results in a dangerous feedback loop of malnutrition 3, 4, 5, 6 and intestinal damage 3, 7, 8, which ultimately leads to growth faltering, poor responses to oral vaccination 9, 10, 11, 12, and diminished resilience to subsequent enteric infections 13. In addition to high mortality rates, diarrhea early in life can have a lasting effect on host physiology 2. Our studies provide valuable insight into the outcomes of diarrheal diseases and growth faltering not attainable in humans and lays the groundwork to test interventions in a controlled and reproducible setting.ĭespite significant improvements in healthcare delivery and sanitation, over 500,000 children under the age of 5 die of diarrheal disease every year 1. We also detected a functional and taxonomic shift in the luminal microbiome across multiple gut sites including the migration of Streptococcus and Prevotella species between the small and large intestine, suggesting a decompartmentalization of gut microbial communities. Moreover, polyclonal stimulation of colonic lamina propria leukocytes resulted in a dampened cytokine response, indicative of immune exhaustion. We show that growth faltering in the presence or absence of active diarrhea is associated with a heightened systemic and mucosal pro-inflammatory state centered in the colon. ![]() Here, we examined intestinal biopsies, lamina propria leukocytes, luminal contents, and fecal samples from healthy infants and those experiencing growth faltering with distant acute or chronic active diarrhea. Infant rhesus macaques are naturally susceptible to human enteric pathogens and recapitulate the hallmarks of diarrheal disease such as intestinal inflammation and growth faltering. Despite the impact of childhood diarrhea on morbidity and mortality, our understanding of its sequelae has been significantly hampered by the lack of studies that examine samples across the entire intestinal tract.
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