Gut bacterial TIR domain NADases in childhood undernutrition
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB48101 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| ERR7881630.fastq.gz | Fastqsanger.gz | |||
| ERR7881640.fastq.gz | Fastqsanger.gz | |||
| ERR7881650.fastq.gz | Fastqsanger.gz | |||
| ERR7881660.fastq.gz | Fastqsanger.gz |
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Project description:Toll/interleukin-1 receptor (TIR) domain proteins are immune signaling components and function as NAD+-cleaving enzymes to activate defense responses. Activation of TIRs represses growth and drives cell death in plants and promotes axon degeneration in animals, but how plant TIRs are repressed remains unclear. Here, we show that TIR NADase activity requires a conserved serine residue spatially close to the catalytic glutamate. The plant Ca2+-dependent protein kinases (CPKs), the mammalian Ca2+/calmodulin-dependent protein kinase II delta (CAMK2D) and TANK binding kinase 1 (TBK1) phosphorylate TIR domains at this conserved serine, which blocks TIR NADase activities and functions and thus maintains growth in plants and suppresses SARM1 TIR signaling in animals, respectively. Our findings define a fundamental molecular mechanism by which phosphorylation at a conserved serine residue blocks TIR signaling to balance growth and defense trade-offs.
2025-06-12 | PXD060014 | Pride
Project description:We illustrate an approach for integrating preclinical gnotobiotic animal models with human studies to understand the contributions of perturbed gut microbiota development to childhood undernutrition, and to identify new microbiota-directed therapeutic concepts/leads. Combining metabolomic and proteomic analyses of serially collected plasma samples with metagenomic analyses of serially collected fecal samples, we characterized the biological state of Bangladeshi children with severe acute malnutrition (SAM) as they transitioned to moderate acute malnutrition (MAM) after standard treatment. Gnotobiotic mice were subsequently colonized with a defined consortium of bacterial strains representing different stages of microbiota development in healthy children from Bangladesh. Administering different combinations of Bangladeshi complementary food ingredients to colonized mice and germ-free controls revealed diet-dependent changes in representation and metabolism of targeted weaning-phase strains, including accompanying increases in branched-chain amino acids, plus diet- and colonization-dependent augmentation of IGF-1/mTOR signaling. Host and microbial effects of microbiota-directed complementary food (MDCF) prototypes were subsequently examined in gnotobiotic mice colonized with post-SAM MAM microbiota and in gnotobiotic piglets colonized with a defined consortium of targeted age- and growth-discriminatory bacteria. Finally, ar andomized, double-blind study revealed a lead MDCF that affected the representation of targeted bacterial taxa and increased levels of biomarkers and mediators of growth, bone formation, neurodevelopment, and immune function.
2019-08-20 | GSE119641 | GEO
Project description:Persistent gut microbiota immaturity in malnourished Bangladeshi children
| PRJEB5482 | ENA
Project description:Toll/interleukin-1 receptor (TIR) domains across different life kingdoms possess NADase activities and produce distinct small molecules including phosphoribosyl adenosine monophosphate/diphosphate (pRib-AMP/ADP) and two cyclic ADPR (cADPR) isomers 2’cADPR and 3’cADPR. Plant intracellular nucleotide-binding leucine-rich repeat (NLR) receptors with an N-terminal TIR domain sense pathogen effectors to initiate immune signaling and rely on downstream helper NLRs to execute immune function. Lipase-like proteins EDS1 and PAD4 transduce immune signals from sensor TIR-NLRs to a helper NLR called ADR1. We report the structure and function of Arabidopsis EDS1-PAD4-ADR1 (EPA) heterotrimer in complex with pRib-AMP/ADP activated by plant or bacterial TIR signaling. Bacterial TIRs that produce 2’cADPR, but not 3’cADPR, induce EPA complex formation and activate EPA signaling using pRib-AMP as the signaling molecule. 2’cADPR is hydrolyzed into pRib-AMP in vivo. 2’cADPR, but not 3’cADPR, induces EPA-dependent defense genes expression. Our findings shed light on the activation mechanisms of ADR1 by EDS1-PAD4 involving two structurally-related molecules with 2’cADPR likely being the storage form of the unstable signaling molecule pRib-AMP, as well as cross-talks between plant and bacterial TIR immune signaling.
2025-01-29 | GSE277725 | GEO
Project description:Effects of current therapeutic foods in undernourished Bangladeshi children compared to microbiota-directed food prototypes in gnotobiotic mice and piglets
2018-04-18 | MSV000082286 | MassIVE
Project description:Intracellular signaling regulators are concentrated into membrane-free, higher-ordered protein assemblies to initiate protective responses during stress — a process known as phase transition. Here, we show that a phase transition of the C. elegans Toll/interleukin-1 receptor domain protein (TIR-1), a homolog of the mammalian sterile alpha and TIR motif-containing 1 (SARM1), primes host immune defenses when dietary sterols are limited to handle subsequent bacterial infection. TIR-1/SARM1 is an upstream component of the p38 PMK-1 pathway in intestinal cells, an innate immune defense and stress response pathway in metazoans. Under conditions of low cholesterol availability, multimerization and precipitation of TIR-1/SARM1 potentiates the intrinsic NAD+ glycohydrolase activity of this protein complex, increases p38 PMK-1 phosphorylation, and promotes pathogen clearance from the intestine. Dietary cholesterol is required for C. elegans to survive infection with pathogenic bacteria and to support development, fecundity, and lifespan. Thus, activation of the p38 PMK-1 pathway in sterol-deficient animals is an adaptive response that allows a metazoan host to anticipate environmental threats under conditions of essential metabolite scarcity.
2022-03-18 | GSE178572 | GEO
Project description:BackgroundPolicy discussions and debates in the last couple of decades emphasized efficiency of development policies for translating economic growth to development. One of the key aspects in this regard in the developing world is achieving improved nutrition through economic development. Nonetheless, there is a dearth of literature that empirically verifies the association between economic growth and reduction of childhood undernutrition in low- and middle-income countries. Thus, the aim of the study is to assess the interplay between economic growth and reduction of childhood undernutrition in Ethiopia.MethodsThe study used pooled data of three rounds (2000, 2005 and 2010) from the Demographic and Health Surveys (DHS) of Ethiopia. A multilevel mixed logistic regression model with robust standard errors was utilized in order to account for the hierarchical nature of the data. The dependent variables were stunting, underweight, and wasting in children in the household. The main independent variable was real per capita income (PCI) that was adjusted for purchasing power parity. This information was obtained from World Bank.ResultsA total of 32,610 children were included in the pooled analysis. Overall, 11,296 (46.7%) [46.0%-47.3%], 8,197(33.8%) [33.2%-34.4%] and 3,175(13.1%) [12.7%-13.5%] were stunted, underweight, and wasted, respectively. We found a strong correlation between prevalence of early childhood undernutrition outcomes and real per capita income (PCI). The proportions of stunting (r = -0.1207, p<0.0001), wasting (r = -0.0338, p<0.0001) and underweight (r = -0.1035, p<0.0001) from the total children in the household were negatively correlated with the PCI. In the final model adjustment with all the covariates, economic growth substantially reduced stunting [β = -0.0016, SE = 0.00013, p<0.0001], underweight [β = -0.0014, SE = 0.0002, p<0.0001] and wasting [β = -0.0008, SE = 0.0002, p<0.0001] in Ethiopia over a decade.ConclusionEconomic growth reduces child undernutrition in Ethiopia. This verifies the fact that the economic growth of the country accompanied with socio-economic development and improvement of the livelihood of the poor. Direct nutrition specific and nutrition sensitive interventions could also be recommended in order to have an impact on the massive reduction of childhood undernutrition in the country.
| S-EPMC4979960 | biostudies-literature
Project description:Introduction:Childhood undernutrition is a crucial public health problem globally. The objective of this study is to measure the prevalence of childhood undernutrition and assess the distinct role of various factors on childhood undernutrition in Bangladesh. Methods:This study utilized the latest cross-sectional data from Bangladesh Demographic and Health Survey 2014. A total of 7256 data on children younger than 5 years old were analyzed. The undernutrition status of children was assessed by stunting (height-for-age), wasting (weight-for-height), and underweight (weight-for-age), while bivariate and multivariate analyses were performed to identify various individual-, household-, and community-level factors of childhood undernutrition. Results:The prevalence of stunting, wasting, and underweight were 36.5%, 14.6%, and 32.5%, respectively. Along with various individual- and household-level factors (eg, age, recent diarrheal disease, fever, number of under-5 children in the household, mother's education and nutritional status, and wealth status), community index, particularly regional and geographic variation of community, had significant role for childhood undernutrition in Bangladesh. Conclusion:Childhood undernutrition is an overwhelming public health issue in Bangladesh. In order to improve the nutritional status of under-5 children, interventions should take into account the various predictors discussed in this study. Indeed, a joint effort by the government, nongovernmental organizations, and the community is necessary to improve the childhood nutritional status in Bangladesh.
| S-EPMC6749788 | biostudies-other
Project description:We have identified statistically significant SNPs influencing susceptibility to diarrhea due to Entamoeba histolytica infection at the locus encoding the transcription factor CREM (10p11.21; rs58000832, P=6.1x10-9; rs2148483, P=9.6x10-8) using genome wide association studies (GWAS). Considering undernutrition increases susceptibility to enteric infection, we investigated if CREM locus variants were also associated with nutritional status. Genetic analysis on birth cohorts of Bangladeshi children demonstrated that risk alleles of rs58000832 and rs2148483 were associated with lower weight-for-age z-scores at 12 months of age (rs2148483: 0.188 reduction in WAZ, P= 0.014; rs58000832: 0.135 reduction in WAZ, P= 0.001), independent of E. histolytica diarrhea. Small intestinal transcriptome data from children homozygous for the rs2148483 risk allele compared to heterozygotes demonstrated enrichment of mitochondrial function and catabolism among upregulated genes and enrichment of B-cell activation and adaptive immune pathways among downregulated genes, consistent with dual roles of the CREM locus in immunity and metabolism. Full body deletion and/or intestinal epithelial cell (IEC)-specific deletion of CREM in mice produced decreased body weight. Transcriptome analysis of cecal tissue from E. histolytica challenged mice also showed upregulation of metabolic processes in both full body and IEC-specific deletion mice. Processes with downregulated genes in full body deletion mice were enriched for myeloid cell activation and chemotaxis while immune process changes were absent when deletion was limited to IECs. These data suggest that CREM modulates both metabolism and immune function at mucosal sites.
2025-05-01 | GSE276451 | GEO
Project description:BackgroundUndernutrition is an important public health indicator for monitoring nutritional status and survival. In spite of its importance, undernutrition is a significant problem health problem in many East African communities. The aim of this study was to identify factors associated with childhood undernutrition in three disadvantaged East African Districts.MethodsWe examined data for 9270 children aged 0-59 months using cross-sectional survey from Gicumbi District in Rwanda, Kitgum District in Uganda and Kilindi District in Tanzania. We considered the level of undernutrition (stunting, wasting and underweight) as the outcome variables with four ordinal categories (severely undernourished, moderately undernourished, mildly undernourished, and nourished). Generalized linear latent and mixed models (GLLAMM) with the mlogit link and binomial family that adjusted for clustering and sampling weights were used to identify factors associated with undernutrition among children aged 0-59 months in three disadvantaged East African Districts.ResultsAfter adjusting for potential confounding factors, the odds of a child being stunted were higher in Gicumbi District in Rwanda while the odds of a child being wasted and underweight were higher in Kitgum District in Uganda. Having diarrhoea two weeks prior to the survey was significantly associated with severe undernutrition. Wealth index (least poor household), increasing child's age, sex of the child (male) and unavailability of water all year were reported to be associated with moderate or severe stunting/wasting. Children of women who did not attend monthly child growth monitoring sessions and children who had Acute Respiratory Infection (ARI) symptoms were significantly associated with moderate or severe underweight.ConclusionsFindings from our study indicated that having diarrhoea, having ARI, not having water availability all year and not attending monthly child growth monitoring sessions were associated with undernutrition among children aged 0-59 months. Interventions aimed at improving undernutrition in these disadvantaged communities should target all children especially those children from households with poor sanitation practices.
| S-EPMC6477742 | biostudies-literature