Associations between Gut Microbiota and Intestinal Inflammation, Permeability and Damage in Young Malawian Children

Abstract

Background Environmental enteric dysfunction (EED) is common in low- and middle-income countries and associated with childhood undernutrition. The composition of gut microbiota has been implicated in the pathogenesis of EED. Our aim was to assess the associations between gut microbiota and EED biomarkers in rural Malawian children. We hypothesized that there would be an inverse association between microbiota maturity and diversity and fecal concentrations of EED biomarkers. Methods We used data from fecal samples collected at 6, 18 and 30 months from 611 children who were followed up during a nutrition intervention trial. The primary time point for analysis was 18 months. Microbiota data were obtained through 16S rRNA sequencing and variables included microbiota maturity and diversity, phylogenetic dissimilarity and relative abundances of individual taxa. EED biomarkers included calprotectin (marker of inflammation), alpha-1 antitrypsin (intestinal permeability) and REG1B (intestinal damage). Results There was an inverse association between microbiota maturity and diversity and fecal concentrations of all 3 EED biomarkers at 18 months (p≤0.001). The results were similar at 30 months, while at 6 months inverse associations were found only with calprotectin and alpha-1 antitrypsin concentrations. At 18 months, EED biomarkers were not associated with phylogenetic dissimilarity, but at 6 and 30 months several associations were observed. Individual taxa predicting EED biomarker concentrations at 18 months included several Bifidobacterium and Enterobacteriaceae taxa as well as potentially displaced oral taxa. Conclusions Our findings support the hypothesis of an inverse association between microbiota maturity and diversity and EED in rural Malawian children.

Dynamics of the Gut Microbiome in Shigella -Infected Children during the First Two Years of Life

“…We found that the alpha diversity increased during the first 2 years of life ( Fig. 2A ), which was consistent with previous reports ( 32 , 54 ). Unlike previous studies that reported a decrease in alpha diversity after diarrheal infection ( 32 , 33 ), we observed in our study that Shigella infection alone did not alter the trajectory of alpha diversity in infants over the first 2 years of life ( Fig.…”

“…To identify changes in the gastrointestinal microbiota that are concomitant with Shigella infection, we compared the alpha diversity at the first Shigella qPCR positive visit in the cases (the index visit) and their matched controls. After adjusting for variables that could affect alpha diversity, including infant age ( 32 , 33 , 38 ), diarrhea ( 32 , 54 ), and antibiotic use ( 55 , 56 ), we determined that the SDI did not differ significantly by Shigella infection status ( P = 0.52) ( Table S2 ). Notably, alpha diversity was significantly associated with infant age ( P < 0.001), diarrhea ( P = 0.012), and recent antibiotic use ( P = 0.017) ( Table S2 ).…”

Lack of Associations between Environmental Exposures and Environmental Enteric Dysfunction among 18-Month-Old Children in Rural Malawi

“…In our study, antibiotic use was inversely associated with calprotectin and alpha-1-antitrypsin concentrations in stools. This result is consistent with findings of a previous study from the iLiNS-DYAD trial, documenting an inverse relationship between antibiotic use and microbiota maturity and diversity that were associated with our three EED biomarkers [ 18 , 19 ].…”

“…To assess the associations of EED with environmental factors concomitantly, we considered other factors as covariates which have been associated with intestinal health [ 18 , 19 ]. In particular, this included breastfeeding, dietary supplementation with small-quantity lipid-based nutrient supplements (SQ-LNS) and antibiotic use, which were reported to be associated with gut microbiome [ 20 , 21 , 22 ].…”

Maternal malnutrition induces in the neonate a lifelong enteropathy avoidable by postnatal S100a8/a9-conditioning

“…Hallmarks of gut dysbiosis in our model were premature expansion of pathobiontic Enterobacteriaceae at the cost of commensal Clostridiaceae. The relevance is corroborated by human studies reporting increased abundances especially of Enterobacteriaceae in MN children 16,18 . Such unfavorable gut microbiota state might certainly promote and maintain the inflammatory gut phenotype 50 , however, assigning gut dysbiosis a truly causative role in EE development needs further clarification in follow-up studies.…”