Daily Rice Bran Consumption for 6 Months Influences Serum Glucagon-Like Peptide 2 and Metabolite Profiles without Differences in Trace Elements and Heavy Metals in Weaning Nicaraguan Infants at 12 Months of Age.

BACKGROUND: Environmental enteric dysfunction (EED) is associated with chronic gut inflammation affecting nutrient absorption and development of children, primarily in low- and middle-income countries. Several studies have shown that rice bran (RB) supplementation provides nutrients and modulates gut inflammation, which may reduce risk for undernutrition. OBJECTIVE: The aim was to evaluate the effect of daily RB dietary supplementation for 6 mo on serum biomarkers in weaning infants and associated changes in serum and stool metabolites. METHODS: A 6-mo randomized-controlled dietary intervention was conducted in a cohort of weaning 6-mo-old infants in León, Nicaragua. Anthropometric indices were obtained at 6, 8, and 12 mo. Serum and stool ionomics and metabolomics were completed at the end of the 6-mo intervention using inductively coupled plasma MS and ultra-high performance LC-tandem MS. The ɑ1-acid glycoprotein, C-reactive protein, and glucagon-like peptide 2 (GLP-2) serum EED biomarkers were measured by ELISA. RESULTS: Twenty-four infants in the control group and 23 in the RB group successfully completed the 6-mo dietary intervention with 90% dietary compliance. RB participants had higher concentrations of GLP-2 as compared with control participants at 12 mo [median (IQR): 743.53 (380.54) pg/mL vs. 592.50 (223.59) pg/mL; P = 0.04]. Metabolite profiles showed significant fold differences of 39 serum metabolites and 44 stool metabolites from infants consuming RB compared with control, and with significant metabolic pathway enrichment scores of 4.7 for the tryptophan metabolic pathway, 5.7 for polyamine metabolism, and 5.7 for the fatty acid/acylcholine metabolic pathway in the RB group. No differences were detected in serum and stool trace elements or heavy metals following daily RB intake for 6 mo. CONCLUSIONS: RB consumption influences a suite of metabolites associated with growth promotion and development, while also supporting nutrient absorption as measured by changes in serum GLP-2 in Nicaraguan infants. This clinical trial was registered at https://clinicaltrials.gov as NCT02615886.

Association between Gut Microbiome Composition and Rotavirus Vaccine Response among Nicaraguan Infants.

Rotavirus is the leading cause of childhood deaths due to diarrhea. Although existing oral rotavirus vaccines are highly efficacious in high-income countries, these vaccines have been demonstrated to have decreased efficacy in low- and middle-income countries. A possible explanation for decreased efficacy is the impact of gut microbiota on the enteric immune system's response to vaccination. We analyzed the gut microbiome of 50 children enrolled in a prospective study evaluating response to oral pentavalent rotavirus vaccination (RV5) to assess associations between relative abundance of bacterial taxa and seroconversion following vaccination. Stool samples were taken before the first RV5 dose, and microbiome composition characterized using 16S rRNA amplicon sequencing and Quantitative Insights Into Microbial Ecology software. Relative abundance of bacterial taxa between seroconverters following the first RV5 dose, those with ≥ 4-fold increase in rotavirus-specific IgA titers, and nonseroconverters were compared using the Wilcoxon-Mann-Whitney test. We identified no significant differences in microbiome composition between infants who did and did not respond to vaccination. Infants who responded to vaccination tended to have higher abundance of Proteobacteria and Eggerthella, whereas those who did not respond had higher abundance of Fusobacteria and Enterobacteriaceae; however, these differences were not statistically significant following a multiple comparison correction. This study suggests a limited impact of gut microbial taxa on response to oral rotavirus vaccination among infants; however, additional research is needed to improve our understanding of the impact of gut microbiome on vaccine response, toward a goal of improving vaccine efficacy and rotavirus prevention.

Rice bran supplementation modulates growth, microbiota and metabolome in weaning infants: a clinical trial in Nicaragua and Mali.

Rice bran supplementation provides nutrients, prebiotics and phytochemicals that enhance gut immunity, reduce enteric pathogens and diarrhea, and warrants attention for improvement of environmental enteric dysfunction (EED) in children. EED is a subclinical condition associated with stunting due to impaired nutrient absorption. This study investigated the effects of rice bran supplementation on weight for age and length for age z-scores (WAZ, LAZ), EED stool biomarkers, as well as microbiota and metabolome signatures in weaning infants from 6 to 12 months old that reside in Nicaragua and Mali. Healthy infants were randomized to a control (no intervention) or a rice bran group that received daily supplementation with increasing doses at each month (1-5 g/day). Stool microbiota were characterized using 16S rDNA amplicon sequencing. Stool metabolomes were analyzed using ultra-high-performance liquid-chromatography tandem mass-spectrometry. Statistical comparisons were completed at 6, 8, and 12 months of age. Daily consumption of rice bran was safe and feasible to support changes in LAZ from 6-8 and 8-12 months of age in Nicaragua and Mali infants when compared to control. WAZ was significantly improved only for Mali infants at 8 and 12 months. Mali and Nicaraguan infants showed major differences in the overall gut microbiota and metabolome composition and structure at baseline, and thus each country cohort demonstrated distinct microbial and metabolite profile responses to rice bran supplementation when compared to control. Rice bran is a practical dietary intervention strategy that merits development in rice-growing regions that have a high prevalence of growth stunting due to malnutrition and diarrheal diseases. Rice is grown as a staple food, and the bran is used as animal feed or wasted in many low- and middle-income countries where EED and stunting is prevalent.

The Association Between Fecal Biomarkers of Environmental Enteropathy and Rotavirus Vaccine Response in Nicaraguan Infants.

BACKGROUND: Environmental enteropathy (EE) is a common intestinal condition among children living in low- and middle-income countries and is associated with diminished enteric immunity to gastrointestinal pathogens, and possibly to oral vaccine antigens. The goal of this study was to examine associations between biomarkers of EE and immunogenicity to the pentavalent rotavirus vaccine (RV5). METHODS: Infants were recruited 1 day before their first RV5 immunization in León, Nicaragua, from public health rosters. Infants provided a preimmunization blood and stool sample, and a second blood sample 1 month after receipt of RV5. We measured immunoglobin A (IgA) seroconversion to the first dose of RV5 and concentrations of 4 previously identified fecal biomarkers of EE (alpha-1 antitrypsin, neopterin, myeloperoxidase and calprotectin). We then assessed associations between concentrations of these biomarkers, both individually and as combined scores, and seroconversion to the first dose of RV5. RESULTS: Of the 43 enrolled infants, 24 (56%) seroconverted after the first dose of RV5. As compared with infants who seroconverted, those who did not seroconvert had higher median concentrations of both myeloperoxidase (3.1 vs. 1.1 µg/mL, P = 0.002) and calprotectin (199.1 vs. 156.2 µg/mL, P = 0.03). Further, those who did not seroconvert had a higher median combined score of the 4 biomarkers as compared with those who seroconverted (6.5 vs. 4.5, P = 0.017). CONCLUSIONS: We found an association between biomarkers of EE and seroconversion to the first dose of RV5. It is possible that interventions that prevent or ameliorate EE may also improve oral rotavirus vaccine response.