نبذة مختصرة : The gut microbiome has an important role in infant health and development. We characterized the fecal microbiome and metabolome of 222 young children in Dhaka, Bangladesh during the first two years of life. A distinct Bifidobacterium longum clade expanded with introduction of solid foods and harbored enzymes for utilizing both breast milk and solid food substrates. The clade was highly prevalent in Bangladesh, present globally (at lower prevalence), and correlated with many other gut taxa and metabolites, indicating an important role in gut ecology. We also found that the B. longum clades and associated metabolites were implicated in childhood diarrhea and early growth, including positive associations between growth measures and B. longum subsp. infantis, indolelactate and N-acetylglutamate. Our data demonstrate geographic, cultural, seasonal, and ecological heterogeneity that should be accounted for when identifying microbiome factors implicated in and potentially benefiting infant development. ; Peer reviewed
Relation: Finally, B. longum subsp. infantis and its associated metabolites, such as indolelactate, were positively correlated with two measures of growth (WFL and WFA) in our cohort, thus adding to a growing body of evidence supporting the importance of B. longum subsp. infantis and its metabolites for infant development (Barratt et al., 2022). We found N-acetylglutamate levels in the stool, as well as two microbial pathways involving N-acetylglutamate, to be positively associated with all tested growth measures including LFA. This observation is notable since bacterially produced N-acetyl amino acids enhanced growth in a Drosophila model (Gallo et al., 2021; Martino et al., 2018). A more recent study provided mechanistic insights on how a related compound, N-acetylglutamine, promoted growth in a Drosophila model via down-regulation of a peptidoglycan recognition protein and immune effectors against beneficial microbes, thus providing an intriguing example of host-microbe symbiosis wherein bacterial metabolic products mediate host immune regulation and growth (Gallo et al., 2021; Martino et al., 2018).We would like to thank participants and their families for their involvement in the study. We thank Tiffany Poon, Luke Besse, and Sara Garamszegi for project management of sample processing and data handling. We thank Florence Rochat, Nadine Porta, Anne Bruttin and Solenn Pruvost for technical assistance in obtaining and sequencing bacterial isolates. We also thank the Broad Institute Genomics Platform and Microbial ‘Omics Core for help with sequencing data generation and sample processing. We are grateful to Heather Kang for editorial assistance. Generation of metagenomics and metabolomics data was supported by a grant from Nestle to the Broad Institute (H.V.). Principal investigators, T.V. O.S. H.V. and R.J.X.; metagenomic data analysis, T.V. Q.Y.A. L.S. and D.R.P.; metabolomic data analysis, T.V. Q.Y.A. M.S. A.D. K.P. K.B. C.D. J.A.-P. and C.B.C.; bacterial isolation and genome sequencing and annotation, L.S. S.D. C.N.-B. and O.S.; phylogenetic and functional genomic analyses: T.V. L.S. S.D. C.N.-B. and O.D.-B.; study design, S.A.S. and T.A.; collection of samples and health information, S.A.S. S.Sayed, S.Sultana, and M.R.; manuscript drafting: T.V. Q.Y.A. L.S. C.I.L.R. C.L.B. D.R.P. S.D. O.D.-B. O.S. and R.J.X. All authors discussed the results, critically reviewed the text, and approved the final manuscript. L.S. C.L.B. C.I.L.R. S.D. O.D-B. C.N-B. and O.S. are employees of Société des Produits Nestlé (SPN). R.J.X. is a member of the Scientific Advisory Board at Nestlé, founder of Jnana and Celsius Therapeutics and board member of MoonLake Immunotherapeutics. We filed a patent related to findings described in this study. R.J.X. H.V. T.V. O.S. L.S. S.D. and C.N.-B. are listed as inventors (Bifidobacterium Longum Transitional Microorganisms, Compositions and Uses Thereof, PCT/US2022/035,310). We would like to thank participants and their families for their involvement in the study. We thank Tiffany Poon, Luke Besse, and Sara Garamszegi for project management of sample processing and data handling. We thank Florence Rochat, Nadine Porta, Anne Bruttin and Solenn Pruvost for technical assistance in obtaining and sequencing bacterial isolates. We also thank the Broad Institute Genomics Platform and Microbial ‘Omics Core for help with sequencing data generation and sample processing. We are grateful to Heather Kang for editorial assistance. Generation of metagenomics and metabolomics data was supported by a grant from Nestle to the Broad Institute (H.V.).; Vatanen , T , Ang , Q Y , Siegwald , L , Sarker , S A , Le Roy , C I , Duboux , S , Delannoy-Bruno , O , Ngom-Bru , C , Boulangé , C L , Stražar , M , Avila-Pacheco , J , Deik , A , Pierce , K , Bullock , K , Dennis , C , Sultana , S , Sayed , S , Rahman , M , Ahmed , T , Modesto , M , Mattarelli , P , Clish , C B , Vlamakis , H , Plichta , D R , Sakwinska , O & Xavier , R J 2022 , ' A distinct clade of Bifidobacterium longum in the gut of Bangladeshi children thrives during weaning ' , Cell , vol. 185 , no. 23 , pp. 4280-4297.e12 . https://doi.org/10.1016/j.cell.2022.10.011; ORCID: /0000-0003-0949-1291/work/128033163; http://hdl.handle.net/10138/573344; 51bb33c1-fd6c-48ca-bf9d-c4596edd9d6e; 85141522383; 000908351600006
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