Title: A synbiotic intervention modulates meta-omics signatures of gut redox potential and acidity in elective Caesarean born infants
|Authors:||C. Lay et al.|
The first 1000 days of life lay the foundation for a child’s future health. During this critical period, the infant’s gut microbiome and immune system rapidly develop.
Multiple factors can impact the gut microbiome and immune system in early life, such as mode of delivery and early exposure to antibiotics. Disrupted gut microbial colonization (unbalanced microbiome) due to, for example, cesarean section delivery may adversely affect the development of the infant gut microbiome. There is a growing body of evidence that indicates that a compromised microbiome in the first 100 days of life is a risk factor for early childhood infections and non-communicable diseases (NCD) later in life.
In a double-blind randomized controlled study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics or a standard control infant formula, from birth until 4 months old. Vaginally born infants were included as a reference group.*
In this study, multi-omics analyses were used to investigate the effects of mode of delivery and early life nutrition on the development of the infant gut microbiome, as well as to reveal possible biological mechanisms behind the role of a compromised microbiome as a risk factor for NCD.
Multi-omics refer to a specific battery of molecular approaches that allows scientists to determine which microbes are present and what they are doing in the infant gut.
The following findings and scientific hypotheses were derived from this study:
– Vaginal birth is associated with the establishment of a healthy gut in the first days of life. Inherited from mums during birth, Bifidobacterium species are early colonizers that play a key role in shaping a healthy gut milieu in infants in the first days of life. Bifidobacteria consume Human Milk Oligosaccharides (HMOS) and ferments them into organic acids (acetic acid and lactic acid), which modulate an acidic environment in the gut. This acidity helps to prevent the growth and establishment of opportunistic pathogens in the infant’s gut.
Based on those insights, the scientists hypothesized that acetic acid would be used by the intestinal cells as a source of energy. This consumption of acetic acid would be associated with the consumption of oxygen by the intestinal cells, preventing the release of oxygen in the gut environment. A healthy gut could be associated with an acidic gut environment free of oxygen.
– C-section birth is associated with a delayed colonization by Bifidobacterium species and early colonization by opportunistic pathogens (Enterobacteriaceae) in the infant’s gut. This indicates that infants born by C-section acquire microbes from the hospital environment.
Microbes belonging to the Enterobacteriaceae do not have the ability to consume human milk oligosaccharides. Because of the absence of bifidobacteria, the HMOS are not fermented into organic acids. The gut environment is therefore less acidic.
Microbes belonging to the Enterobacteriaceae can therefore thrive in the gut of infants born by C-section. They consume oxygen (respiration), metabolize reactive oxygen species and produce endotoxins (lipopolysaccharides).
The production of endotoxins and presence of oxidative stress as a reflection of reactive oxygen metabolism, might underline the role of a compromised gut microbiome. Additional scientific research is needed to determine the clinical implication.
Based on the above insights, the scientists hypothesized that the depletion of acetic acid due to the lack of Bifidobacterium, would disturb the metabolism of the intestinal cells. This allows the release of oxygen by the intestinal cells in the gut environment and favors the growth of opportunistic pathogens. Therefore, an unhealthy gut could be associated to a less acidic and a more oxidative gut environment.
– A synbiotic infant formula (a combination of scGOS/lcFOS and Bifidobacterium breve M-16V) administered to infants born by C-section restored the delayed colonization by Bifidobacterium and prevented the establishment of a compromised microbiome in the first 100 days of life. This was translated to the establishment of an acidic gut environment devoid of oxygen.
In conclusion, a tailored nutritional solution containing synbiotics may contribute to support the healthy growth and development of infants born with a compromised microbiome and reduce the disease risk associated with C-section birth.
*The results of this study were revealed in an earlier publication. Please find more here.