Modeling Enteropathy or Diarrhea with the Top Bacterial and Protozoal Pathogens: Differential Determinants of Outcomes

Abstract

Developing effective therapeutics or preventive interventions for important health threats is greatly enhanced whenever accessible models can enable the assessment of clinically important outcomes. While no non-human model is ever perfect, inexpensive in vivo small animal models in such as mice are often of great help in assessing the relevant efficacy of potential interventions. In addition to acute diarrhea, the long-term growth and developmental effects of enteric infections, with or without overt diarrhea, are increasingly recognized. To address these diverse effects, inexpensive animal models are proving to be very helpful. Herein, we review the major clinical concerns with enteric parasitic and bacterial infections that are extremely common worldwide, especially in vulnerable young children living in impoverished areas, and the recently published murine models of these infections and their outcomes. We find that common dietary deficiencies seen in children in developing areas have striking effects on diarrhea and enteropathy outcomes in mice. However, these effects differ with different pathogens. Specifically, the effects of protein or zinc deficiency differ considerably with different major protozoal and bacterial pathogens, suggesting different pathogenetic pathways and intervention effects. The pathogens reviewed are the seven top parasitic and bacterial pathogens seen in children, namely, Cryptosporidium , Giardia , Campylobacter , Shigella , enterotoxigenic Escherichia coli (ETEC), enteroaggregative E. coli (EAEC), and enteropathogenic E. coli (EPEC).

Dynamics of the Gut Microbiome in Shigella -Infected Children during the First Two Years of Life

“…Each group of children was composed of 50% males and females. Length for age z scores (LAZ), a measure for stunting which has been associated with Shigella infection in children ( 9 , 45 – 48 ), did not significantly differ between the case and control groups at birth or at 24 months of age ( Table 1 ).…”

“…It is an invasive enteric pathogen that causes mucosal inflammation and the disruption of the intestinal barrier ( 5 , 6 ), leading to watery diarrhea and dysentery (bloody diarrhea) ( 4 ). Frequent and repeated bouts of diarrheal disease in children result in debilitating sequelae, including impaired growth and stunting, deficits in cognitive development, and an increased risk of metabolic syndrome ( 7 – 9 ), which can result in lifelong health impairments ( 10 , 11 ). The transmissibility and clinical severity of disease in this vulnerable group, along with the emergence of antibiotic-resistant strains, make Shigella prevention a public health priority.…”

Characterization of Enteric Disease in Children by Use of a Low-Cost Specimen Preservation Method

“…Importantly, the data demonstrate that the five most prevalent pathogens remain the same regardless of age. Research on the causal pathways contributing to environmental enteropathy, stunting, and other long-term negative health outcomes among infants and young children in LMICs indicates that even asymptomatic colonization with these enteropathogens should be a public health concern, since it may impact growth, cognitive development, and long-term economic productivity ( 3 , 19 , 20 ) Additionally, we found high rates of Shigella and ETEC in age groups older than 5 years, confirming the importance of these two pathogens in older children and adolescents ( 21 ).…”

The synergistic interaction of systemic inflammation, dysbiosis and antimicrobial resistance promotes growth restriction in children with acute severe malnutrition: An emphasis on Escherichia coli

“…Protein or zinc Mouse model Protein or zinc deficiency, profoundly alters weight loss, pathogen shedding, and biomarkers of intestinal disruption in EAEC, ETEC, Shigella, and Campylobacter infections in mouse model (Bolick et al, 2014;Guerrant et al, 2021).…”