Diet at birth is critical for healthy growth, independent of effects on the gut microbiota

Study information

Reviewed Marked as Reviewed by Svetlana up on 2024-10-17

study design

laboratory experiment

Citation

PMID PubMed identifier for scientific articles.

39068488

DOI Digital object identifier for electronic documents.

10.1186/s40168-024-01852-7

URI

Authors

van den Elsen LJW, Rekima A, Lynn MA, Isnard C, Machado S, Divakara N, Patalwala D, Middleton A, Stevens N, Servant F, Burcelin R, Lynn DJ, Verhasselt V

Journal

Microbiome

Year

2024

Keywords:

Breast milk, Colostrum, Growth failure, Growth hormone resistance, Neonatal microbiota

BACKGROUND: Colostrum is the first milk for a newborn. Its high content in microbiota shaping compounds and its intake at the time of gut microbiota seeding suggests colostrum may be critical in the establishment of a healthy microbiota. There is also accumulating evidence on the importance of the gut microbiota for healthy growth. Here, we aimed to investigate the contribution of colostrum, and colostrum-induced microbiota to growth promotion. Addressing this question is highly significant because (1) globally, less than half of the newborns are fully colostrum fed (2) the evidence for the importance of the microbiota for the prevention of undernutrition has only been demonstrated in juvenile or adult pre-clinical models while stunting already starts before weaning. RESULTS: To address the importance of diet at birth in growth failure, we developed a unique mouse model in which neonates are breastfed by mothers at an advanced stage of lactation who no longer provide colostrum. Feeding newborn mice with mature milk instead of colostrum resulted in significant growth retardation associated with the biological features of chronic undernutrition, such as low leptin levels, dyslipidemia, systemic inflammation, and growth hormone resistance. We next investigated the role of colostrum in microbiota shaping. At the end of the lactation period, we found a major difference in gut microbiota alpha diversity, beta diversity, and taxa distribution in control and colostrum-deprived mice. To determine the causal relationship between changes in microbiota and growth trajectories, we repeated our experiment in germ-free mice. The beneficial effect of colostrum on growth remained in the absence of microbiota. CONCLUSION: Our data suggest that colostrum may play an important role in the prevention of growth failure. They highlight that the interplay between neonatal gut microbiome assembly and diet may not be as crucial for growth control in the developing newborn as described in young adults. This opens a paradigm shift that will foster research for colostrum's bioactives that may exert a similar effect to microbiota-derived ligands in promoting growth and lead to new avenues of translational research for newborn-tailored prevention of stunting. Video Abstract.

Experiment 1

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Reviewed Marked as Reviewed by Svetlana up on 2024-10-17

Curated date: 2024/10/08

Curator: Princess Ben

Revision editor(s): Princess Ben

Subjects

Location of subjects: Australia

Host species Species from which microbiome was sampled. Contact us to have more species added.: Mus musculus

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Postnatal growth retardation Growth delay as children,Growth retardation as children,Postnatal growth deceleration,Postnatal growth deficiency,Postnatal growth failure,Postnatal growth retardation,postnatal growth retardation

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Control

Group 1 name Corresponds to the case (exposed) group for case-control studies: Colostrum-deprived mice

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Newborn mice deprived of colostrum, fed with mature milk.

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): NA

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 2

Alpha Diversity

Simpson Estimator of species richness and species evenness: more weight on species evenness: increased

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa: increased

Signature 1

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Reviewed Marked as Reviewed by Svetlana up on 2024-10-17

Curated date: 2024/10/08

Curator: Princess Ben

Revision editor(s): Princess Ben, Svetlana up

Source: Figure 4D

Description: Differential abundance in colostrum-deprived mice compared to the control mice.

Abundance in Group 1: increased abundance in Colostrum-deprived mice

NCBI	Quality Control	Links
Candidatus Saccharimonas
Marvinbryantia
Rikenellaceae
unclassified Oscillospiraceae
Clostridia vadin BB60 groupClostridia vadin BB60 group
Rikenellaceae RC9Rikenellaceae RC9
Candidatus Saccharimonadaceae