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Personalized modeling of gut microbiome metabolism throughout the first year of life
Rola Shaaban1,2, Susheel Bhanu Busi3,4, Paul Wilmes3,5
1Inserm UMRS 1256 NGERE, University of Lorraine, Nancy, France.
Insights
Cesarian section delivery alters infant gut microbiome metabolism, reducing key metabolites early in life. This study developed a metabolic modeling workflow to analyze these early-life gut microbiome changes.
Area of Science:
- Microbiome research
- Infant metabolism
- Computational biology
Background:
- Early-life exposures, including diet and gut microbiome, influence infant health and disease predisposition.
- Cesarean section delivery disrupts infant gut microbiome establishment, potentially leading to adverse long-term outcomes.
- Cesarean section may alter both the composition and metabolic functions of the developing infant gut microbiome.
Purpose of the Study:
- To investigate how Cesarean section delivery impacts the metabolic capabilities of the infant gut microbiome.
- To develop and apply a metabolic modeling workflow for analyzing infant gut microbiome metabolism.
Main Methods:
- Expanded the AGORA2 resource with a human milk oligosaccharide degradation module.
- Performed personalized metabolic modeling of gut microbiomes from 20 infants over their first year and 13 maternal samples.
- Utilized genome-scale reconstructions for microbial metabolic modeling.
Main Results:
- Infants delivered via Cesarean section showed depleted gut microbiome metabolic capabilities compared to vaginally delivered infants at early stages.
- Specific metabolites, including fermentation products, human milk oligosaccharide degradation products, and amino acids, were reduced in Cesarean section group microbiomes.
- Infant gut microbiomes produced less butyrate and more L-lactate than maternal microbiomes, with enrichment in B-vitamin synthesis potential.
Conclusions:
- Metabolic capabilities of the infant gut microbiome are significantly altered by Cesarean section delivery, particularly in the earliest developmental stages.
- The developed metabolic modeling workflow can be applied to diverse cohorts to assess factors like feeding type and maternal diet on early-life host-gut microbiome interactions.
Background:
Early-life exposures including diet, and the gut microbiome have been proposed to predispose infants towards multifactorial diseases later in life. Delivery via Cesarian section disrupts the establishment of the gut microbiome and has been associated with negative long-term outcomes. Here, we hypothesize that Cesarian section delivery alters not only the composition of the developing infant gut microbiome but also its metabolic capabilities. To test this, we developed a metabolic modeling workflow targeting the infant gut microbiome.
Methods:
The AGORA2 resource of human microbial genome-scale reconstructions was expanded with a human milk oligosaccharide degradation module. Personalized metabolic modeling of the gut microbiome was performed for a cohort of 20 infants at four time points during the first year of life as well as for 13 maternal gut microbiome samples.
Results:
Here we show that at the earliest stages, the gut microbiomes of infants delivered through Cesarian section are depleted in their metabolic capabilities compared with vaginal delivery. Various metabolites such as fermentation products, human milk oligosaccharide degradation products, and amino acids are depleted in Cesarian section delivery gut microbiomes. Compared with maternal gut microbiomes, infant gut microbiomes produce less butyrate but more L-lactate and are enriched in the potential to synthesize B-vitamins.
Conclusions:
Our simulations elucidate the metabolic capabilities of the infant gut microbiome demonstrating they are altered in Cesarian section delivery at the earliest time points. Our workflow can be readily applied to other cohorts to evaluate the effect of feeding type, or maternal factors such as diet on host-gut microbiome inactions in early life.
