Rotavirus vaccines have poor efficacy in infants from low- and middle-income countries. Gut microbiota is thought to influence the immune response to oral vaccines. Thus, we developed a gnotobiotic (Gn) pig model of enteric dysbiosis to study the effects of human gut microbiota (HGM) on immune responses to rotavirus vaccination, and the effects of rotavirus challenge on the HGM by colonizing Gn pigs with healthy HGM (HHGM) or unhealthy HGM (UHGM). The UHGM was from a Nicaraguan infant with a high enteropathy score (ES) and no seroconversion following administration of oral rotavirus vaccine, while the converse was characteristic of the HHGM. Pigs were vaccinated, a subset was challenged, and immune responses and gut microbiota were evaluated. Significantly more rotavirus-specific IFN-γ producing T cells were in the ileum, spleen, and blood of HHGM than those in UHGM pigs after three vaccine doses, suggesting HHGM induces stronger cell-mediated immunity than UHGM. There were significant correlations between multiple Operational Taxonomic Units (OTUs) and frequencies of IFN-γ producing T cells at the time of challenge. There were significant positive correlations between Collinsella and CD8+ T cells in blood and ileum, as well as CD4+ T cells in blood, whereas significant negative correlations between Clostridium and Anaerococcus, and ileal CD8+ and CD4+ T cells. Differences in alpha diversity and relative abundances of OTUs were detected between the groups both before and after rotavirus challenge. Alterations in microbiome diversity and composition along with correlations between certain microbial taxa and T cell responses warrant further investigation into the role of the gut microbiota and certain microbial species on enteric immunity. Our results support the use of HGM transplanted Gn pigs as a model of human dysbiosis during enteric infection, and oral vaccine responses.

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.

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 (Oryza sativa L.) processing yields ~60 million metric tons of bran annually. Rice genes producing bran metabolites of nutritional and human health importance were assessed across 17 diverse cultivars from seven countries using non-targeted metabolomics, and resulted in 378–430 metabolites. Gambiaka cultivar had the highest number and Njavara had the lowest number of metabolites. The 71 rice bran compounds of significant variation by cultivar included 21 amino acids, seven carbohydrates, two metabolites from cofactors and vitamins, 33 lipids, six nucleotides, and two secondary metabolites. Tryptophan, α-ketoglutarate, γ-tocopherol/β-tocopherol, and γ-tocotrienol are examples of bran metabolites with extensive cultivar variation and genetic information. Thirty-four rice bran components that varied between cultivars linked to 535 putative biosynthetic genes using to the OryzaCyc 4.0, Plant Metabolic Network database. Rice genes responsible for bran composition with animal and human health importance is available for rice breeding programs to utilize in crop improvement.

Campylobacteriosis is an important contributor to the global burden of acute gastroenteritis (AGE). In Nicaragua, the burden, risk factors, and species diversity for infant campylobacteriosis are unknown. Between June 2017 and December 2018, we enrolled 444 infants from León, Nicaragua, in a population-based birth cohort, conducting weekly household AGE surveillance. First, we described clinical characteristics of symptomatic Campylobacter infections, and then compared clinical characteristics between Campylobacter jejuni/coli and non-jejuni/coli infections. Next, we conducted a nested case–control analysis to examine campylobacteriosis risk factors. Finally, we estimated the population attributable fraction of campylobacteriosis among infants experiencing AGE. Of 296 AGE episodes in the first year of life, Campylobacter was detected in 59 (20%), 39 were C. jejuni/coli, and 20 were non-jejuni/coli species, including the first report of Campylobacter vulpis infection in humans. Acute gastroenteritis symptoms associated with C. jejuni/coli lasted longer than those attributed to other Campylobacter species. In a conditional logistic regression model, chickens in the home (odds ratio [OR]: 3.8, 95% CI: 1.4–9.8), a prior AGE episode (OR: 3.3; 95% CI: 1.4–7.8), and poverty (OR: 0.4; 95% CI: 0.2–0.9) were independently associated with campylobacteriosis. Comparing 90 infants experiencing AGE with 90 healthy controls, 22.4% (95% CI: 11.2–32.1) of AGE episodes in the first year of life could be attributed to Campylobacter infection. Campylobacter infections contribute substantially to infant AGE in León, Nicaragua, with non-jejuni/coli species frequently detected. Reducing contact with poultry in the home and interventions to prevent all-cause AGE may reduce campylobacteriosis in this setting.

Rice bran supplementation provides nutrients, prebiotics and phytochemicals that enhance gut immunity, reduce enteric pathogens in mice and diarrhea in neonatal pigs, and warranted attention for improvement of environmental enteric dysfunction (EED) in children at risk. EED is a condition that drives childhood stunting via intestinal dysbiosis and impaired nutrient metabolism. This study investigated effects of rice bran supplementation on growth, EED biomarkers, gut microbiome and metabolome in weaning infants from 6 to 12 months old in Nicaragua and Mali. Healthy infants were randomized to a control group or rice bran group that received daily supplementation at increasing doses each month. Stool microbiomes 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 for infant growth, decreasing alpha-1 antitrypsin levels, and modulating gut microbiome and metabolome when compared to control. Rice bran merits investigation as a practical intervention strategy that could decrease EED prevalence and risk for children from low- and middle-income countries where rice is grown as a staple food, and bran is used as animal feed or wasted. One Sentence Summary: Dietary rice bran supplementation during infant weaning from 6-12 months of age improved growth outcomes, modulated environmental enteric dysfunction biomarkers, and supported metabolism by the gut microbiome. The authors declare no competing financial or non financial interests to disclose as defined by Nature Research. There are also no other interests that might be perceived to influence the results and/or discussion reported in this paper. Correspondence and requests for materials should be addressed to Dr. Elizabeth Ryan ( e.p.ryan@colostate.edu ).