Microbiota Determinants in Early Life and Their Immunologic Health Consequences

The gut microbiota plays a major role in the development and function of immune protective mechanisms (e.g., those associated with risk of infectious disease), as
well as immunomodulatory functions (e.g., those associated with risk of allergy, inflammatory bowel disease, neoplasia). The development of this complex
ecosystem in each infant is driven by multiple determinant factors: genetic, maternal (including prenatal), and environmental. While many environmental factors, including geography, family structure, pets, antibiotics, play a role; by far, the mode of birth
(cesarean versus vaginal delivery) and the type of feeding (breast feeding versus other substitutes) appear to be the most significant modulators of the early development of each individual’s microbiota.

Breastfeeding promotes microbiota development with significant diversity and predominance of specific species, particularly bifidobacteria and lactobacilli, via
multiple mechanisms, including breast milk bacteria composition and human milk oligosaccharides. Non-breastfed infants develop dysbiosis–generally described as
altered gut microbiota profiles and changes in diversity, as compared to breastfed. Clinically, breastfed infants are generally protected from a number of health conditions
associated with use of breast milk substitutes. These include lower risk from infections, and immunological disease such as asthma, other allergies, type one diabetes, and
leukemia, as well as metabolic disease (obesity and type 2 diabetes). Notably, all these health conditions have been associated with dysbiosis later in life.

Similarly, compared with vaginal birth, birth by cesarean section has been associated with a less diverse microbiota, and altered microbial profiles, including lower presence of bifidobacteria1. Increasingly, strong associations have been reported between cesarean delivery and disease in infancy and later life.2

Cesarean delivery increases risk of gastroenteritis, respiratory infections, and otitis media. It has also been shown to be strongly associated with risk of hospitalizations
for acute gastroenteritis in the first two years of life, and this risk is exacerbated
further for those who are not breastfeed.3 Cesarean birth also increases risk of obesity4 and type 2 diabetes. Most notably, it increases risk of allergic disease, including asthma, atopic dermatitis, and particularly food allergy.5 And the relative risk of leukemia, particularly acute lymphocytic leukemia appears also to be increased.6

Of note, all these conditions are also associated with dysbiosis. Most studies so far linking cesarean birth to disease are associative and long-term prospective studies are underway. However, alterations in microbial composition, diversity, and maturity
appear to precede some of these manifestations.7 It is increasingly becoming clear that the development of early life dysbiosis (resulting from determining factors such as cesarean section and lack of breastfeeding) is a major link, and potentially an etiologic
factor in the risk expression of multiple acute and chronic conditions. The use of specific species and strains of bifidobacteria (e.g., B. infantis, B. lactis) and lactobacilli (L. rhamnosus, L. reuteri) as probiotics has been shown to have effects on infectious intestinal and respiratory illness, and have effect on modulating gut barrier function, IgA
secretion, and T lymphocytes activity modulation. Thus, probiotics may have the potential for mitigating the dysbiosis associated with cesarean birth of lack of
breastfeeding and its longer-term immune related consequences.