Enteric pathogens through life stages

Abstract

Enteric infections and diarrheal diseases constitute pervasive health burdens throughout the world, with rates being highest at the two ends of life. During the first 2-3 years of life, much of the disease burden may be attributed to infection with enteric pathogens including Salmonella, rotavirus, and many other bacterial, viral, and protozoan organisms; however, infections due to Clostridium difficile exhibit steady increases with age. Still others, like Campylobacter infections in industrialized settings are high in early life (<2 years old) and increase again in early adulthood (called the "second weaning" by some). The reasons for these differences undoubtedly reside in part in pathogen differences; however, host factors including the commensal intestinal microbial communities, immune responses (innate and acquired), and age-dependant shifts likely play important roles. Interplay of these factors is illustrated by studies examining changes in human gut microbiota with inflammatory bowel disease and irritable bowel syndrome. Recent gut microbial surveys have indicated dramatic shifts in gut microbial population structure from infants to young adults to the elders. An understanding of the evolution of these factors and their interactions (e.g., how does gut microbiota modulate the "inflamm-aging" process or vice versa) through the human life "cycle" will be important in better addressing and controlling these enteric infections and their consequences for both quality and quantity of life (often assessed as disability adjusted life-years or "DALYs").

Keywords: age distribution; diarrhea; enteric pathogen; intestinal microbiota; malnutrition.

Figure 1

Differences between “healthy” and malnourished intestinal mucosa are represented by architectural changes (villi height/crypt depth, crypt hypertrophy), molecular changes (tight junction alteration, nutrient absorption), immune changes, and the intestinal microbiota. Cross-talk between the intestinal microbiota and intestinal mucosa through metabolites is unclear.

Figure 2

Age-dependent mortality rates due to diarrhea (A) or protein-energy malnutrition (B) based on 2008 WHO data. Numbers of diarrheal or malnutrition from the Global Burden of Disease in 2008 cases were compared to the total population sum of each WHO region (2012). WHO regions were grouped into four categories (i.e., low, low-middle, upper-middle, and upper) based on Gross National Income (GNI) brackets established by the World Bank (2012). The GNI income bracket most represented within a WHO region was used to combine data. For example, the Region of Americas (AMRB) consists of 26 countries, the majority of which (n = 18) are classified as upper-middle income countries and were therefore included in the upper-middle income data. The low-income (red line) category consists of African Region (AFR D and E) and South East Asian Region (SEAR D); low-middle (green line) consists of Region of the Americas (AMR D), Eastern Mediterranean Region (EMR D), Western Pacific Region (WPR B), and SEAR B; upper-middle (blue line) consists of AMR B, EMR B, and European Region (EURB and C); upper (grey line) consists of AMR A, EUR A, and WPR A. The mortality rate data are limited by the use of all-age population data, so actual age-dependent rates may differ.

Figure 3

Predominant commensal and pathogenic microbes associated with human life stages. Color intensity of each bar correlates with presence or absence of commensal bacteria at the phylum (underlined) with examples listed below using noted references. Studies characterizing fecal microbiota prior to 2007 quantify the viable counts of bacteria, while later studies use DNA based methods.