r.i.c.e.

This post is a little deeper in the scientific details than r.i.c.e. readers may be used to, but I hope you will stick with us, because it is important. Evidence is building up that enteropathy may matter a great deal. This week, Andrew Prendergast and nine coauthors published a new paper in PLOS ONE: “Stunting Is Characterized by Chronic Inflammation in Zimbabwean Infants.” They collected data on about 14,000 infants at periodic intervals in their first 18 months of life. Among the ones with data all along, they ended up with a sample of 101 stunted infants – meaning too short – and 101 non-stunted infants, in order to have healthy comparison group.

The paper is important because it speaks to the hypothesis of enteropathy as a determinant of stunting among poor children who grow up exposed to intestinal disease. They write “Poor linear growth begins in utero, continues during the first 2 years of life and is largely irreversible thereafter. Despite its high prevalence, the reasons for stunting among children living in impoverished conditions remain uncertain. Although inadequate diet contributes to poor growth, the best nutritional interventions have only a modest impact on stunting. Diarrhea has been implicated in the causal pathway to stunting but, possibly because children frequently show catch-up growth between diarrheal episodes, the association has been surprisingly weak in many studies. The role of the gut in mediating stunting has been relatively overlooked until recently, when attention has refocused on the possible contribution of enteropathy to poor growth in early life.

“It was recognized almost 50 years ago that people living in impoverished conditions almost universally had an abnormality of the small intestine, characterized by villous blunting, inflammatory infiltrate and increased intestinal permeability. This apparently asymptomatic condition was termed tropical enteropathy, although it became clear that environmental conditions, rather than geography per se, were the critical determinant. It is hypothesized that frequent exposure to feco-oral bacteria in conditions of poor sanitation and hygiene drives a T-cell mediated process that has been renamed environmental enteropathy.”

So, what do these new data say about this hypothesis? Sure enough, stunted children showed more signs of enteropathy, on average. But what is even more interesting is that the damage appears to begin in utero. Mothers, too show signs of inflammation: “Although we selected cases and controls at 18 months of age, stunted infants were already growth restricted at birth. Median height-for-age Z-score at birth among these infants was −1.00 and almost one-quarter of infants in the stunted group had low birth weight. Birth weight was related to infant IGF-1 at birth, which in turn was associated with the inflammatory status of the mother-infant dyad. The infant inflammatory milieu was closely related to the level of maternal inflammation at birth. We speculate, based on these associations, that inflammation during pregnancy may ‘set’ the infant inflammatory axis, which in turn influences the level of IGF-1 in early life.” If you’re still with me, that’s http://en.wikipedia.org/wiki/Insulin-like_growth_factor.

I’m not a biological expert, and the authors point to the need for further research, but across a range of studies, evidence is accumulating that enteropathy could mean early-life exposure to open defecation is an even bigger deal than people may realize. “Antenatally, maternal nutritional and inflammatory status may impact fetal growth, leading to intrauterine stunting and low birth weight; postnatally, low-grade inflammation early in life is associated with stunting.” Maternal nutrition is complex, but could exposure to fecal pathogens matter for development even before birth?