Diarrhea as a Potential Cause and Consequence of Reduced Gut Microbial Diversity Among Undernourished Children in Peru.

BACKGROUND: Detrimental effects of diarrhea on child growth and survival are well documented, but details of the underlying mechanisms remain poorly understood. Recent evidence demonstrates that perturbations to normal development of the gut microbiota in early life may contribute to growth faltering and susceptibility to related childhood diseases. We assessed associations between diarrhea, gut microbiota configuration, and childhood growth in the Peruvian Amazon. METHODS: Growth, diarrhea incidence, illness, pathogen infection, and antibiotic exposure were assessed monthly in a birth cohort of 271 children aged 0-24 months. Gut bacterial diversity and abundances of specific bacterial taxa were quantified by sequencing 16S rRNA genes in fecal samples collected at 6, 12, 18, and 24 months. Linear and generalized linear models were used to determine whether diarrhea was associated with altered microbiota and, in turn, if features of the microbiota were associated with the subsequent risk of diarrhea. RESULTS: Diarrheal frequency, duration, and severity were negatively associated with bacterial diversity and richness (P < .05). Children born stunted (length-for-age z-score [LAZ] ≤ -2) who were also severely stunted (LAZ ≤ -3) at the time of sampling exhibited the greatest degree of diarrhea-associated reductions in bacterial diversity and the slowest recovery of bacterial diversity after episodes of diarrhea. Increased bacterial diversity was predictive of reduced subsequent diarrhea from age 6 to 18 months. CONCLUSIONS: Persistent, severe growth faltering may reduce the gut microbiota's resistance and resilience to diarrhea, leading to greater losses of diversity and longer recovery times. This phenotype, in turn, denotes an increased risk of future diarrheal disease and growth faltering.

A Longitudinal Study of Household Water, Sanitation, and Hygiene Characteristics and Environmental Enteropathy Markers in Children Less than 24 Months in Iquitos, Peru.

Poor child gut health, resulting from a lack of access to an improved toilet or clean water, has been proposed as a biological mechanism underlying child stunting and oral vaccine failure. Characteristics related to household sanitation, water use, and hygiene were measured among a birth cohort of 270 children from peri-urban Iquitos Peru. These children had monthly stool samples and urine samples at four time points and serum samples at (2-4) time points analyzed for biomarkers related to intestinal inflammation and permeability. We found that less storage of fecal matter near the household along with a reliable water connection were associated with reduced inflammation, most prominently the fecal biomarker myeloperoxidase (MPO) (no sanitation facility compared with those with an onsite toilet had -0.43 log MPO, 95% confidence interval [CI]: -0.74, -0.13; and households with an intermittent connection versus those with a continuous supply had +0.36 log MPO, 95% CI: 0.08, 0.63). These results provide preliminary evidence for the hypothesis that children less than 24 months of age living in unsanitary conditions will have elevated gut inflammation.

Astrovirus Infection and Diarrhea in 8 Countries.

BACKGROUND AND OBJECTIVES: Astroviruses are important drivers of viral gastroenteritis but remain understudied in community settings and low- and middle-income countries. We present data from 8 countries with high prevalence of diarrhea and undernutrition to describe astrovirus epidemiology and assess evidence for protective immunity among children 0 to 2 years of age. METHODS: We used 25 898 surveillance stools and 7077 diarrheal stools contributed by 2082 children for enteropathogen testing, and longitudinal statistical analysis to describe incidence, risk factors, and protective immunity. RESULTS: Thirty-five percent of children experienced astrovirus infections. Prevalence in diarrheal stools was 5.6%, and severity exceeded all enteropathogens except rotavirus. Incidence of infection and diarrhea were 2.12 and 0.88 episodes per 100 child-months, respectively. Children with astrovirus infection had 2.30 times the odds of experiencing diarrhea after adjustment for covariates (95% confidence interval [CI], 2.01-2.62; P < .001). Undernutrition was a risk factor: odds of infection and diarrhea were reduced by 10% and 13%, respectively, per increase in length-for-age z score (infection: odds ratio, 0.90 [95% CI, 0.85-0.96]; P < .001; diarrhea: odds ratio, 0.87 [95% CI, 0.79-0.96]; P = .006). Some evidence of protective immunity to infection was detected (hazard ratio, 0.84 [95% CI, 0.71-1.00], P = .052), although this was heterogeneous between sites and significant in India and Peru. CONCLUSIONS: Astrovirus is an overlooked cause of diarrhea among vulnerable children worldwide. With the evidence presented here, we highlight the need for future research as well as the potential for astrovirus to be a target for vaccine development.