Abstract
BackgroundEnvironmental enteropathy (EE) is an asymptomatic abnormality of small bowel structure and function, which may underlie vaccine inefficacy in the developing world. HIV infection co-exists in many of these populations. There is currently no effective treatment. We conducted a secondary analysis of a randomised controlled trial of high dose multiple micronutrient (MM) supplementation on small bowel architecture in EE in participants with or without HIV infection.MethodsIn a double-blind parallel-group trial of the effect of MM on innate immune responses to oral vaccines, consenting Zambian adults were randomised to receive 6 weeks of 24 micronutrients as a daily capsule or placebo. HIV status was established after randomisation. Proximal jejunal biopsies were obtained after the supplementation period. Villous height, crypt depth, villous width, villous perimeter per 100 μm muscularis mucosa (a measure of epithelial surface area), and villous cross sectional area per 100 μm muscularis mucosa (a measure of villous compartment volume) were measured in orientated biopsy sections using semi-automated image analysis. Analysis was by intention to treat.Results18 patients received MM and 20 placebo. 6/18 MM and 9/20 placebo patients had HIV. In HIV negative patients given MM compared to placebo, mean villous height was 24.0% greater (293.3 v. 236.6 μm; 95% CI of difference 17.7–95.9 μm; P = 0.006), mean villous area was 27.6% greater (27623 v. 21650 μm2/100 μm; 95% CI of difference 818–11130 μm2/100 μm; P = 0.03), and median villous perimeter was 29.7% greater (355.0 v. 273.7 μm/100 μm; 95% CI of difference 16.3–146.2 μm/100 μm; P = 0.003). There was no significant effect on crypt depth or villous width. No effect was observed in HIV positive patients. There were no adverse events attributable to MM.ConclusionsMM improved small bowel villous height and absorptive area, but not crypt depth, in adults with EE without HIV. Nutritional intervention may therefore selectively influence villous compartment remodelling. In this small study, there was a clear difference in response depending on HIV status, suggesting that EE with superimposed HIV enteropathy may be a distinct pathophysiological condition.
Highlights
Environmental enteropathy (EE) is an asymptomatic abnormality of small bowel structure and function, which may underlie vaccine inefficacy in the developing world
In Human immunodeficiency virus (HIV) negative patients given multiple micronutrient (MM) compared to placebo, mean villous height (VH) was 24.0% greater (293.3 v. 236.6 μm; mean difference 56.8 μm [95% confidence interval 17.7 – 95.9 μm]; P = 0.006, 2-tailed t test), mean villous cross sectional area (VA) per 100 μm of mucosa was 27.6% greater (27623 v. 21650 μm2/ 100 μm; mean difference 5973 μm2/100 μm [818 – 11130 μm2/100 μm]; P = 0.03, 2-tailed t test), and median villous perimeter (VP) per 100 μm of mucosa was 29.7% greater (355.0 μm/ 100 μm v. 273.7 μm/100 μm; median difference 81.3 μm/100 μm [16.3 – 146.2 μm/100 μm]; P = 0.003, Kruskal-Wallis) (Figure 4)
As a result of improved VH in HIV negative patients given MM, villous:crypt (V:C) ratio was 1.56:1 with placebo v. 1.83:1 with MM (95% confidence interval of ratio following treatment 1.63:1 – 2.03:1; P = 0.01, 2-tailed t test)
Summary
Environmental enteropathy (EE) is an asymptomatic abnormality of small bowel structure and function, which may underlie vaccine inefficacy in the developing world. It is thought to be the result of recurrent exposure to gastrointestinal pathogens [1], but could be explained by other factors including nutrient deficiencies It is characterised by abnormal villous and crypt architecture, heightened T cell-mediated inflammation and increased epithelial permeability secondary to impaired tight junction function [2,3] which results in reduced small bowel absorptive capacity, increased microbial translocation and systemic inflammation [4]. This predisposes to poor growth in children [4] and malabsorption in people of all ages. EE is increasingly recognised as being of critical importance in global health [1]
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