The molecular epidemiology of chronic aflatoxin driven impaired child growth

Abstract

Aflatoxins are toxic secondary fungal metabolites that contaminate dietary staples in tropical regions; chronic high levels of exposure are common for many of the poorest populations. Observations in animals indicate that growth and/or food utilization are adversely affected by aflatoxins. This review highlights the development of validated exposure biomarkers and their use here to assess the role of aflatoxins in early life growth retardation. Aflatoxin exposure occurs in utero and continues in early infancy as weaning foods are introduced. Using aflatoxin-albumin exposure biomarkers, five major studies clearly demonstrate strong dose response relationships between exposure in utero and/or early infancy and growth retardation, identified by reduced birth weight and/or low HAZ and WAZ scores. The epidemiological studies include cross-sectional and longitudinal surveys, though aflatoxin reduction intervention studies are now required to further support these data and guide sustainable options to reduce the burden of exposure. The use of aflatoxin exposure biomarkers was essential in understanding the observational data reviewed and will likely be a critical monitor of the effectiveness of interventions to restrict aflatoxin exposure. Given that an estimated 4.5 billion individuals live in regions at risk of dietary contamination the public health concern cannot be over stated.

Figure 1

Structures of the major naturally occurring aflatoxins. Aflatoxin B1 dominates the natural occurrence and is the most toxic and carcinogenic.

Figure 2

Structures of the two major aflatoxin B1 epoxides. The exo-epoxide is both toxic and carcinogenic; the endo-epoxide is only toxic.

Figure 3

Structures of the aflatoxin species measured is validated exposure biomarkers. Aflatoxin-lysine is the digest product of aflatoxin-albumin detected in sera, AFM1 is the hydroxy metabolite detected in urine, and aflatoxin-N7-guanine is the depurination product of aflatoxin-DNA adducts.

Figure 4

Selected biotransformation pathways for the aflatoxins. Focus on AFB1 biotransformations which are highlighted and indicate the route to the specific biomarkers. Biotransformation of AFB2 to AFB1 will be modest and likely represent less than 1% of the dose of AFB2. The AFG2 pathway is predicted, but likely of low or very modest contribution. Modified from [21, 22].

Figure 5

A timeline for the discovery and identification of aflatoxin and key studies in animals and humans on growth in relation to dosing or natural exposure, respectively. Human data only includes validated exposure biomarker driven studies; additional human studies published between 1989 and 2010 further support these observations (see text). Modified from [21, 22, 136].