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Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition.

ABSTRACT: Diarrheal diseases continue to contribute significantly to morbidity and mortality in infants and young children in developing countries. There is an urgent need to better understand the contributions of novel, potentially uncultured, diarrheal pathogens to severe diarrheal disease, as well as distortions in normal gut microbiota composition that might facilitate severe disease.We use high throughput 16S rRNA gene sequencing to compare fecal microbiota composition in children under five years of age who have been diagnosed with moderate to severe diarrhea (MSD) with the microbiota from diarrhea-free controls. Our study includes 992 children from four low-income countries in West and East Africa, and Southeast Asia. Known pathogens, as well as bacteria currently not considered as important diarrhea-causing pathogens, are positively associated with MSD, and these include Escherichia/Shigella, and Granulicatella species, and Streptococcus mitis/pneumoniae groups. In both cases and controls, there tend to be distinct negative correlations between facultative anaerobic lineages and obligate anaerobic lineages. Overall genus-level microbiota composition exhibit a shift in controls from low to high levels of Prevotella and in MSD cases from high to low levels of Escherichia/Shigella in younger versus older children; however, there was significant variation among many genera by both site and age.Our findings expand the current understanding of microbiota-associated diarrhea pathogenicity in young children from developing countries. Our findings are necessarily based on correlative analyses and must be further validated through epidemiological and molecular techniques.

SUBMITTER: Pop M

PROVIDER: S-EPMC4072981 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition.

Pop Mihai M Walker Alan W AW Paulson Joseph J Lindsay Brianna B Antonio Martin M Hossain M Anowar MA Oundo Joseph J Tamboura Boubou B Mai Volker V Astrovskaya Irina I Corrada Bravo Hector H Rance Richard R Stares Mark M Levine Myron M MM Panchalingam Sandra S Kotloff Karen K Ikumapayi Usman N UN Ebruke Chinelo C Adeyemi Mitchell M Ahmed Dilruba D Ahmed Firoz F Alam Meer Taifur MT Amin Ruhul R Siddiqui Sabbir S Ochieng John B JB Ouma Emmanuel E Juma Jane J Mailu Euince E Omore Richard R Morris J Glenn JG Breiman Robert F RF Saha Debasish D Parkhill Julian J Nataro James P JP Stine O Colin OC

Genome biology 20140627 6

<h4>Background</h4>Diarrheal diseases continue to contribute significantly to morbidity and mortality in infants and young children in developing countries. There is an urgent need to better understand the contributions of novel, potentially uncultured, diarrheal pathogens to severe diarrheal disease, as well as distortions in normal gut microbiota composition that might facilitate severe disease.<h4>Results</h4>We use high throughput 16S rRNA gene sequencing to compare fecal microbiota composit ...[more]

PMID: 24995464

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Project description:ImportanceClimate change is associated with more frequent and intense floods. Current research on the association between flood exposure and diarrhea risk is limited mainly to short-term and event-specific analyses. Moreover, how prior drought or water, sanitation, and hygiene (WaSH) practices influence this association remains largely unknown.ObjectiveTo examine the association between flood exposure and diarrhea risk among children younger than 5 years and to evaluate the compounding influence of prior drought and effect modification by WaSH.Design, setting, and participantsThis cross-sectional study included multicluster surveys conducted by the Demographic and Health Surveys Program in 43 low- and middle-income countries during 2009 through 2019. This study included children younger than 5 years in all households from each survey cluster. Collected data were analyzed between September 1 and December 31, 2022.ExposuresHistorical flood events during 2009 through 2019 were obtained from the Dartmouth Flood Observatory.Main outcome and measuresThe main outcome was diarrhea prevalence among children younger than 5 years in the 2 weeks before the survey was conducted. Results were analyzed by binomial generalized linear mixed-effects logistic regression models with nested random intercepts for country and survey cluster.ResultsAmong 639 250 children making up the complete data series (excluding 274 847 children with missing values for diarrhea or baseline characteristics), 6365 (mean [SD] age, 28.9 [17.2] months; 3214 boys [50.5%]; 3151 girls [49.5%]) were exposed to floods during the 8 weeks after a flood started. The prevalence of diarrhea was 13.2% (n = 839) among exposed children and 12.7% (n = 80 337) among unexposed children. Exposure to floods was associated with increased diarrhea risk, with the highest odds ratio (OR) observed during the second to fourth weeks after floods started (OR, 1.35; 95% CI, 1.05-1.73). When floods were stratified by severity and duration, significant associations were observed only for extreme floods (OR during the third to fifth weeks, 2.07; 95% CI, 1.37-3.11) or floods lasting more than 2 weeks (OR during the second to fourth weeks, 1.47; 95% CI, 1.13-1.92), with significantly stronger associations than for less extreme floods or shorter-duration floods, respectively. The OR during the first 4 weeks after the start of floods was significantly higher for floods preceded by a 6-month or longer drought (12-month drought OR, 1.96; 95% CI, 1.53-2.52) than for floods not preceded by a 6-month or longer drought (12-month drought OR, 1.00; 95% CI, 0.79-1.27).ConclusionsThese findings suggest that floods, especially severe floods, long-duration floods, and floods preceded by drought, are associated with an increased risk of diarrhea among children younger than 5 years living in low- and middle-income countries. With the projected increasing frequency and intensity of floods and drought under climate change, greater collective efforts are needed to protect children's health from these compounding events.

Project description:IntroductionThe diversity and dysregulation of intestinal microbiota is related to the pathology of epilepsy. Gut microbiota plays an important role in epilepsy, and regulating intestinal microbiota through exogenous intervention can alleviate symptoms. However, there are no studies about the effects of epilepsy-related diarrhea on gut microbiota.MethodsThe diversity and dysregulation of intestinal microbiota is related to the pathology of epilepsy. Gut microbiota plays an important role in epilepsy, and regulating intestinal microbiota through exogenous intervention can alleviate symptoms. However, there are no studies about the effects of epilepsy-related diarrhea on gut microbiota. To evaluate changes in gut microbiota structure and composition in patients with epilepsy and associated diarrhea, the structure and composition of the fecal microbiota among patients with epilepsy (EP, 13 cases), epilepsy with diarrhea (ED, 13 cases), and probiotic treatments (PT, 13 cases), and healthy controls (CK, seven cases) were investigated and validated by utilizing high-throughput 16S rRNA sequencing.ResultsThe results showed that the α-diversity indexes indicated that richness and phylogenetic diversity had no significant differences among groups. However, the variation of β-diversity indicated that the structure and composition of intestinal microbiota were significantly different among the CK, EP, ED, and PT groups (permutational multivariate analysis of variance, p-value = 0.001). Normalized stochasticity ratio and β-nearest taxon index indicated that stochastic mechanisms exerted increasing influence on community differences with epilepsy and associated diarrhea. ED microbiome alterations include increased Proteobacteria and decreased Actinobacteria and Firmicutes at the phylum level. Bifidobacterium was the core microbe in CK, EP, and PT, whereas it decreased significantly in ED. In contrast, Escherichia/Shigella was the core microbe in CK and ED, whereas it increased significantly in ED (Tukey's multiple comparisons test, adjusted p-value <0.05). The association network in CK has higher complexity and aggregation than in the other groups. The EP network indicated high connectivity density within each community and high sparsity among communities. The bacterial community network of the ED had a more compact local interconnection, which was in contrast to that of PT. The top 7 microbial amplicon sequence variant-based markers that were selected by machine learning to distinguish the groups of epilepsy, probiotic treatments, and healthy infants had stronger discrimination ability. In addition, ASVs_1 (Escherichia/Shigella) and ASVs_3 (Bifidobacterium) had the most importance in the recognition.DiscussionOur research finally showed that infants with epilepsy, epilepsy with diarrhea, and probiotic treatments exhibit substantial alterations of intestinal microbiota structure and composition, and specific intestinal strains are altered according to different clinical phenotypes and can therefore be used as potential biomarkers for disease diagnosis.

Project description:Altered gut microbiota are assumed to be involved in the pathogenesis of irritable bowel syndrome (IBS). However, gut microbiota alterations reported in different studies are divergent and sometimes even contradictory. To better elucidate the relationship between altered gut microbiota and IBS, we characterized fecal microbiota of diarrhea-predominant IBS (IBS-D) patients and further explored the effect of rifaximin on gut microbiota using bacterial 16S rRNA gene-targeted pyrosequencing. In our study, IBS-D patients defined by Rome III criteria and age-and-gender matched healthy controls (HC) were enrolled to investigate the fecal microbiota alterations. These IBS-D patients were then treated with rifaximin for 2 weeks and followed up for 10 weeks. Fecal microbiota alterations, small intestine bacterial overgrowth (SIBO) and gastrointestinal (GI) symptoms of IBS-D patients were analyzed before and after treatment. Our results showed fecal microbiota richness but not diversity was decreased in IBS-D patients as compared to HC and there were alterations of fecal microbiota at different taxonomy levels. The abundant phyla Firmicutes was significantly decreased and Bacteroidetes was increased in IBS-D patients. Moreover, the alterations of predominant fermenting bacteria such as Bacteroidales and Clostridiales might be involved in the pathophysiology of IBS-D. In addition, rifaximin was effective in terms of SIBO eradication and even GI symptoms of IBS-D patients achieved at least 10-week improvement after treatment. Furthermore, rifaximin induced alterations of some special bacteria rather than affected the overall composition of microbiota in IBS-D patients. Meanwhile, a potential decrease in propanoate and butanoate metabolism was found in these IBS-D patients after rifaximin treatment. Taken together, there were alterations of gut microbiota in IBS-D patients as compared to HC. Rifaximin could relieve GI symptoms, modify gut microbiota in IBS-D patients and eradicate SIBO in those patients with SIBO, suggesting an additional therapeutic mechanism of rifaximin in the treatment of IBS-D. Our findings of compositional gut microbiota alterations in IBS-D and the effect of rifaximin on the gut microbiota implied that altered gut microbiota were associated with the pathogenesis of IBS.

Dataset Information

Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition.

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Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition.

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