Project description:- Background: Optimized diets during the first period of life may be most effective for improving gut and overall health. Here, we set up an interdisciplinary research pipeline to evaluate gut health benefits of early life nutrition ingredients through advanced integration of in vitro and modeling technologies that represent the infant gut environment. - Methods: In our InTESTine platform (TM), biopts of piglet gut tissue (Jejunum or Colon) were exposed (0-6h) to various infant/piglet-formula-milk based food matrices (-/+ prebiotics; -/+ predigestion by infant/piglet fecal microbiome). RNA expression of the piglet gut tissue biopts was measured by RNAseq. - Results: To be published in various papers. - Conclusion: To be published in various papers.
Project description:Diet-microbe interactions play a crucial role in infant development and modulation of the early-life microbiota. The genus Bifidobacterium dominates the breast-fed infant gut, with strains of B. longum subsp. longum (B. longum) and B. longum subsp. infantis (B. infantis) particularly prevalent within the early-life microbiota. Although, transition from milk to a more diversified diet later in infancy initiates a shift to a more complex microbiome, with concurrent reductions in Bifidobacterium abundance, specific strains of B. longum may persist in individual hosts for prolonged periods of time. Here, we sought to investigate the adaptation of B. longum to the changing infant diet during the early-life developmental window. Genomic characterisation of 75 strains isolated from nine either exclusively breast- or formula-fed infants in the first 18 months of their lives revealed subspecies- and strain-specific intra-individual genomic diversity with respect to glycosyl hydrolase families and enzymes, which corresponded to different dietary stages. Complementary phenotypic growth studies indicated strain-specific differences in human milk oligosaccharide and plant carbohydrate utilisation profiles between and within individual infants, while proteomic profiling identified proteins involved in metabolism of selected carbohydrates. Our results indicate a strong link between infant diet and B. longum subspecies/strain genomic and carbohydrate utilisation diversity, which aligns with a changing nutritional environment i.e. moving from breast milk to a solid food diet. These data provide additional insights into possible mechanisms responsible for the competitive advantage of this bifidobacterial species and their long-term persistence in a single host and may contribute to rational development of new dietary therapies for this important development window.
Project description:Microbiota assembly in the infant gut is influenced by time and duration of dietary exposure to breast-milk, infant formula and solid foods. In this randomized controlled intervention study, longitudinal sampling of infant stools (n=998) showed similar development of fecal bacterial communities between formula- and breast-fed infants during the first year of life (N=210). Infant formula supplemented with galacto-oligosaccharides (GOS) was most efficient to sustain high levels of bifidobacteria compared to formula containing B. longum and B. breve or placebo. Metabolite (untargeted) and bacterial profiling (16S rRNA/shallow metagenomics sequencing) revealed 24-hour oscillations and integrated data analysis identified circadian networks. Rhythmicity in bacterial diversity, specific taxa and functional pathways increased with age and was most pronounced following breast-feeding and GOS-supplementation. Circadian rhythms in dominant taxa were discovered ex-vivo in a chemostat model. Hence microbiota rhythmicity develops early in life, likely due to bacterial intrinsic clock mechanism and is affected by diet.
Project description:<p>Rural communities in resource-limited settings are exposed to seasonal patterns in food insecurity. The pre- and early post-natal period is a key developmental window, sensitive to nutritional availability and quality. While season of birth has been associated with differences in epigenetic, developmental and health outcomes, it is unclear if this imprints on the developing metabolome and contributes to adverse phenotypic outcomes. Here we show that infant urinary and plasma metabolites in Tanzanian infants follow seasonal waveforms dependent upon their month of birth, persisting up to at least 18 months of life, which were related to food insecurity, breastmilk composition and rainfall. This includes developmentally relevant metabolites, including choline, trimethylamine-N-oxide, and polyunsaturated fatty acids. Cognitive measures at 18 months also followed seasonal waveforms based upon month of birth which correlated with seasonal metabolites. Additionally, variation in metabolic status modulated the effectiveness of a maternal-infant nicotinamide intervention targeting stunting. Our findings show that seasonal environmental pressures shape mother-infant dyad food insecurity with lasting ramifications for the infant metabolome and development. These findings support the need for season-dependent nutritional and lifestyle interventions targeting developmental shortfalls in these communities.</p>
Project description:<p>Infancy is a critical period for the colonization of the gut microbiome. However, xenobiotic effects on gut microbiome development in early life remain poorly understood. Here, we recruit 146 mother-infant pairs and collect stool samples at 3, 6, and 12 months after delivery for amplicon sequencing (N = 353), metagenomics (N = 65), and metabolomics (N = 198). Trace elements in maternal hair samples (N = 119) affect the alpha diversity of the infant gut microbiome. Shannon diversity in 3-month-old infants is correlated positively with selenium and negatively with copper, and the relative abundance of Bifidobacterium increases under high exposure to aluminum and manganese. During the first year of life, infants and their paired mothers have distinct microbial diversity and composition, and their bacterial community structures gradually approach. There are 56 differential metabolites between the first and second postpartum visits and 515 differential metabolites between the second and third visits. The typical profile of antibiotic resistance genes (ARGs) differs significantly between infants and their mothers. High copper and arsenic exposure may induce the enrichment of ARGs in the infant gut. Our findings highlight the dynamics of the gut microbiome, metabolites, and ARG profiles of mother-infant pairs after delivery, associated with prenatal exposure to trace elements.</p>