A Randomized Controlled Trial of Dietary Rice Bran Intake on Microbiota Diversity, Enteric Dysfunction, and Fecal Secretory IgA in Malian and Nicaraguan Infants

Abstract

Background: Malnutrition and diarrhea are leading causes of death in children aged <5 y. Rice bran is a nutrient-dense prebiotic available globally.

Objectives: The objective of this secondary analysis was to evaluate the effects of daily rice bran supplementation on environmental enteric dysfunction (EED) markers, total fecal secretory IgA (sIgA), and microbiota in infants at high risk of malnutrition.

Methods: Six-month-old Malian and Nicaraguan infants were randomly assigned to control or daily rice bran supplementation cohorts (1 to 5 g/d). Feces were collected monthly for 6 mo to evaluate fecal sIgA, markers of EED, and microbiota diversity. Statistical methods included linear mixed models, generalized mixed models, Spearman correlation, and Wilcoxon rank-sum tests.

Results: Six-month-old Malian infants had significantly elevated sIgA (4.0× higher, P < 0.001), fecal myeloperoxidase (31.6× higher, P < 0.001), fecal α1-antitrypsin (1.8× higher, P = 0.006), and lower fecal neopterin (0.13× higher, P < 0.001) than the age-matched Nicaraguan infants. In the Nicaraguan rice bran cohort from 6 to 12 mo of age, there was a significant decrease in sIgA concentrations (0.4×, P < 0.05) and a correlation between sIgA and the EED marker α1-antitrypsin (0.523, P < 0.0001) at 12 mo of age. In Malian infants, daily rice bran ingestion resulted in decreased EED scores (0.71×, P = 0.02) and a stable sIgA concentration over time. The rice bran group of Malian infants also had correlation between sIgA and the EED marker neopterin (0.544, P < 0.001) at 12 mo of age and a significant (P < 0.05) increase in microbiota α-diversity at a younger age (9 mo with rice bran compared with 10 mo in control group), which supports earlier microbiota maturation.

Conclusions: These results support rice bran as a functional food ingredient targeting gut mucosa in children at high-risk of malnutrition.

Keywords: Mali; Nicaragua; environmental enteric dysfunction; fecal secretory IgA; prebiotic; rice bran.

FIGURE 1

Total fecal sIgA (A) and EED markers (B) in 6-mo-old Malian (n = 48) and Nicaraguan (n = 46) infants. Values presented are mean ± SD. *,**Significant difference between the 2 cohorts: *P < 0.05, **P < 0.001. Data on the y-axis are log₁₀ transformed. EED, environmental enteric dysfunction; sIgA, secretory IgA.

FIGURE 2

Total fecal sIgA (A) and 4-component EED scores (B) in Malian and Nicaraguan infants from 6 to 12 mo of age. Values presented are mean ± SD. Mali control cohort (n = 24), Mali rice bran cohort (n = 24), Nicaragua control cohort (n = 24), Nicaragua rice bran cohort (n = 22). Data on the y-axis are log₁₀ transformed. Total number of diarrheal episodes in Mali children (C) are shown for both the control (n = 20) and rice bran (n = 8) groups. *,**Significantly different comparison: *P < 0.05, **P < 0.001. EED, environmental enteric dysfunction; sIgA, secretory IgA.

FIGURE 3

Fecal microbiota α-diversity index shown for Chao1 (A) and Shannon diversity (B) for the control and rice bran groups in Mali at 6, 9, 10, and 11 mo of age. Mali control cohort (n = 24), Mali rice bran cohort (n = 24), *P < 0.001, **P < 0.05. boxplots represent Q1, median, Q3. Q1 = Quartile 1 = 25th percentile. Q3 = Quartile 3 = 75th percentile. The Chao and Shannon index are comparing the 9, 10 and 11 months to 6 months of age.

FIGURE 4

Malian infant log-fold gut microbiota differences between control and rice bran cohorts at 6, 9, 10, and 11 mo of age. White bars indicate the operational taxonomic units (OTUs) that were increased in rice bran group and black bars indicate the OTUs increased in the control group. Changes were considered significant if the log-fold change was >2 with a P < 0.01. The 34 genera and species are depicted out of 122 that were identified as significantly different over time (see Supplemental Figure 1 for complete list).