Characterizing Bifidobacterium longum subspecies infantis strains in undernourished Bangladeshi infants and gnotobiotic mice
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ABSTRACT:
PROVIDER: PRJEB45396 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| ERR6158410.fastq.gz | Fastqsanger.gz | |||
| ERR6158580.fastq.gz | Fastqsanger.gz | |||
| ERR6158590.fastq.gz | Fastqsanger.gz | |||
| ERR6158600.fastq.gz | Fastqsanger.gz |
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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:Bifidobacterium longum subsp. infantis (B. infantis) colonizes the infant gut microbiome with a 43-kb gene cluster that enables human milk oligosaccharide (HMO) utilization. Although there is relative genomic homogeneity in this regard, previous observations suggest that B. infantis strains may differ in their utilization phenotype. To test this hypothesis, a panel of B. infantis strains were evaluated for their ability to utilize pooled HMOs to yield differential phenotypes including biomass accumulation, HMO consumption glycoprofile, end-product secretion, and global transcriptomes. Two strains (ATCC 15697 and UMA301) efficiently consumed several HMO isomers/anomers that exhibit degrees of polymerization (DP) ³ 4. These same strains partially consumed the smaller DP HMOs including fucosyllactose and lactodifucotetraose isomers/anomers. In contrast, UMA299 efficiently utilized fucosylated small molecular weight HMOs (DP<4), and accumulated greater biomass on purified 2´FL with significantly higher 1,2-propanediol production. This study identifies several strain-dependent features in HMO utilization phenotypes that are consistent with metabolic variation within a bifidobacterial-dominated infant-gut microbiome.
2020-12-30 | GSE164005 | 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:Probiotics have rarely been studied in young healthy infants from low-income countries. This phase I study investigated the safety and acceptability of two probiotics in Bangladesh.Healthy infants aged four to twelve weeks from urban slums in Bangladesh were randomized to one of three different intervention dosing arms (daily, weekly, biweekly - once every two weeks) of Lactobacillus reuteri DSM 17938 and Bifidobacterium longum subspecies infantis 35624 over one month or to a fourth arm that received no probiotics. All subjects were followed for two additional months. Reported gastrointestinal and respiratory symptoms as well as breastfeeding rates, hospitalizations, differential withdrawals, and caretakers' perception of probiotic use were compared among arms.In total, 160 infants were randomized (40 to each arm) with 137 (Daily n?=?35, Weekly n?=?35, Biweekly n?=?35, Control n?=?32) followed up for a median of twelve weeks; 113 completed the study. Illness and breastfeeding rates were similar across all arms. Ten hospitalizations unrelated to probiotic use occurred. Forty eight percent of the caretakers of infants in intervention arms believed that probiotics improved their baby's health.These two commonly used probiotics appeared safe and well-accepted by Bangladeshi families.ClinicalTrials.gov NCT01899378 . Registered July 10, 2013.
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Project description:Bifidobacterium longum subsp. infantis (B. infantis) resides in the human infant gut and helps with the utilization of human milk-derived nutrient components. While its utilization of various carbohydrate sources has been studied extensively, mechanisms behind utilization of nitrogen components from human milk remain largely unknown. In this study, we present B. infantis growth profiles on the N-containing human milk oligosaccharides (HMO) as nitrogen sources, namely, lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT). Dietary 2-Oxoglutarate (2-OG) in known in mice model for its protective effects against intestinal inflammation and colitis development. In this study, we have shown that B. infantis had increased 2-OG concentration when utilizes LNT or LNnT as a primary nitrogen source. As LNT and LNnT are the isomers of HMO core structures, N-acetyl glucosamine (NAG), the N-containing monosaccharide, was regarded as the nitrogen provider of the HMO core structures. Differentially expressed gene patterns in B. infantis were analyzed under the less efficient nitrogen conditions (HMOs and NAG) relative to the complex nitrogen controls. Proteomics analysis of B. infantis using 15N-labeled NAG revealed that NAG nitrogen was incorporated into B. infantis metabolism. Transcriptomics results of B. infantis in LNT, LNnT and NAG nitrogen were consistent with the proteomics results. This further indicated that B. infantis metabolism was affected by NAG nitrogen in nitrogen assimilation, HMO catabolism, NAD cofactor biosynthesis and regeneration, and peptidoglycan biosynthesis pathways. In summary, B. infantis can use NAG-containing HMO as a nitrogen source and incorporate NAG nitrogen into metabolism pathways.
2023-09-14 | GSE209665 | GEO
Project description:Prior studies of Bangladeshi migrants in the UK revealed that reproductive function is adaptive, responding to different environments during childhood by adjusting the timing of puberty, reproductive lifespan and overall reproductive function. Here we aimed to understand the basis of this plasticity. Our goals were to establish whether epigenetic mechanisms play a role in the plasticity of this adaptive reproductive phenotype. We hypothesized that women growing up in Bangladesh would have distinct DNA methylation signatures compared to those who moved to the UK at a young age or were born to Bangladeshi parents in the UK. Some of these environmentally induced epigenetic differences would be detected in buccal cell DNA and reflect the divergent gene expression responsible for the altered reproductive function. The women of the study who grew up in Bangladesh were relatively affluent, well-nourished and rarely performed manual work, but a significant confounding factor in their early life was the level of disease load presenting a chronic immune challenge
2019-06-27 | GSE133355 | GEO
Project description:Disrupted development of the gut microbiota is a contributing cause of childhood malnutrition. Bifidobacterium longum subspecies infantis is a prominent early colonizer of the infant gut that consumes human milk oligosaccharides (HMOs). We found that the absolute abundance of Bifidobacterium infantis is lower in 3- to 24-month-old Bangladeshi infants with severe acute malnutrition (SAM) compared to their healthy age-matched counterparts. A single-blind, placebo-controlled trial (SYNERGIE) was conducted in 2- to 6-month-old Bangladeshi infants with SAM. A commercial U.S. donor-derived B. infantis strain (EVC001) was administered daily with or without the HMO lacto-N-neotetraose for 28 days. This intervention increased fecal B. infantis abundance in infants with SAM, although to levels still 10- to 100-fold lower than in untreated healthy controls. EVC001 treatment promoted weight gain that was associated with reduced intestinal inflammation markers in infants with SAM. We cultured fecal B. infantis strains from Bangladeshi infants and colonized gnotobiotic mice with these cultured strains. The gnotobiotic mice were fed a diet representative of that consumed by 6-month-old Bangladeshi infants, with or without HMO supplementation. One B. infantis strain, Bg_2D9, expressing two gene clusters involved in uptake and utilization of N-glycans and plant-derived polysaccharides, exhibited superior fitness over EVC001. The fitness advantage of Bg_2D9 was confirmed in a gnotobiotic mouse model of mother-to-infant gut microbiota transmission where dams received a pretreatment fecal community from a SAM infant in the SYNERGIE trial. Whether Bg_2D9 is superior to EVC001 for treating malnourished infants who consume a diet with limited breastmilk requires further clinical testing.
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Project description:15N-labeled N-acetylglucosamine (NAG) fed to B. infantis cells are incorporated into its proteome. This indicates that NAG, an amino sugar residue of human milk oligosaccharides (HMO) and other biopolymers, is used as a nitrogen source. Transcriptomics while subsisting on NAG nitrogen are consistent with the proteomics results. This further indicates that B. infantis utilizes NAG nitrogen in and shunts it towards a fundamental cellular processes.
2023-05-18 | PXD035809 | Pride
Project description:The deposited microarray data were generated in a study that integrated the gene expression profiles and metabolic responses of Caco2 cells incubated with Bifidobacterium infantis subsp. infantis and Salmonella enterica subsp. enterica sv. Typhimurium. The aim of this study was to investigate the interaction of B. infantis, S. Typhimurium, and host cells (Caco2) in the course of infection to understand the molecular mechanics of probiotic-pathogen-host interactions.
2024-05-08 | GSE266880 | GEO
Project description:A microbiota-directed complementary food intervention improves stunting in undernourished Bangladeshi children
| PRJEB66487 | ENA