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An In Vitro Batch-culture Model to Estimate the Effects of Interventional Regimens on Human Fecal Microbiota
Published on: July 31, 2019
A synbiotic intervention modulates meta-omics signatures of gut redox potential and acidity in elective caesarean
Christophe Lay1, Collins Wenhan Chu2, Rikky Wenang Purbojati3
1Danone Nutricia Research, Singapore, Singapore.
Insights
C-section birth can compromise infant gut microbiomes, increasing non-communicable disease risk. Synbiotic formula helps restore a healthy gut environment, preventing this compromise in infants.
Area of Science:
- Microbiome research
- Infant nutrition
- Non-communicable disease (NCD) risk factors
Background:
- C-section delivery is linked to a compromised gut microbiome, a potential risk factor for non-communicable diseases (NCDs).
- Investigating the impact of delivery mode and infant nutrition on gut microbiome development is crucial for understanding NCD pathogenesis.
Purpose of the Study:
- To investigate the impact of delivery mode and infant nutrition on the developing infant gut microbiome.
- To uncover biological mechanisms linking a compromised microbiome to NCD risk.
- To evaluate the efficacy of synbiotic-supplemented formula in counteracting C-section-induced microbiome disturbances.
Main Methods:
- Double-blind randomized controlled study of 153 infants born via elective C-section.
- Infants received formula supplemented with synbiotics, prebiotics, or unsupplemented until 4 months.
- Vaginally born infants served as a reference group.
- Stool sample analysis using multi-omics from day 3 to week 22.
Main Results:
- Vaginally born infants showed an early hypoxic, acidic gut with Bifidobacteriaceae enrichment.
- C-section infants exhibited a compromised microbiome with Enterobacteriaceae enrichment and altered gene expression.
- Synbiotic formula modulated microbial genes, promoting an environment similar to vaginally born infants and preventing microbiome compromise.
Conclusions:
- C-section birth establishes a distinct, compromised infant gut microbiome with specific functional hallmarks.
- Synbiotic supplementation can effectively modulate the infant gut microbiome, counteracting C-section-induced disturbances.
- This research provides insights into preventing NCDs by optimizing infant gut microbiome development.
Background:
The compromised gut microbiome that results from C-section birth has been hypothesized as a risk factor for the development of non-communicable diseases (NCD). In a double-blind randomized controlled study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics, or unsupplemented from birth until 4 months old. Vaginally born infants were included as a reference group. Stool samples were collected from day 3 till week 22. Multi-omics were deployed to investigate the impact of mode of delivery and nutrition on the development of the infant gut microbiome, and uncover putative biological mechanisms underlying the role of a compromised microbiome as a risk factor for NCD.
Results:
As early as day 3, infants born vaginally presented a hypoxic and acidic gut environment characterized by an enrichment of strict anaerobes (Bifidobacteriaceae). Infants born by C-section presented the hallmark of a compromised microbiome driven by an enrichment of Enterobacteriaceae. This was associated with meta-omics signatures characteristic of a microbiome adapted to a more oxygen-rich gut environment, enriched with genes associated with reactive oxygen species metabolism and lipopolysaccharide biosynthesis, and depleted in genes involved in the metabolism of milk carbohydrates. The synbiotic formula modulated expression of microbial genes involved in (oligo)saccharide metabolism, which emulates the eco-physiological gut environment observed in vaginally born infants. The resulting hypoxic and acidic milieu prevented the establishment of a compromised microbiome.
Conclusions:
This study deciphers the putative functional hallmarks of a compromised microbiome acquired during C-section birth, and the impact of nutrition that may counteract disturbed microbiome development.
Trial Registration:
The study was registered in the Dutch Trial Register (Number: 2838 ) on 4th April 2011.

