| Immune system dysregulation |
Allergy |
|
Inverse association of bacterial diversity in the early intestinal flora 1 and 12 mo after birth with the risk of allergic sensitization (serum-specific IgE; peripheral blood eosinophils and allergic rhinitis) Low prevalence of Bacteroides and Bifidobacterium spp. associated with atopic dermatitis |
Reduced bacterial diversity of the infants’ intestinal flora associated with an increased risk of allergic sensitization, allergic rhinitis, and peripheral blood eosinophilia Percentages of Bifidobacterium significantly lower in patients with severe skin symptoms Staphylococcus significantly higher in patients with atopic dermatitis |
Clinical |
Bisgaard et al. (2011)82
|
| Clinical |
Watanabe et al. (2003)72
|
Asthma “Hygiene hypothesis” |
Chronic inflammatory disease of the airways |
Increased risk of asthma and atopy in children born by C-section; demonstrated using a combination of 2 methods: 1) evaluation of registers and questionnaire (symptoms in the child and the family) and 2) clinical examination (delivery history and general pediatric clinical examination) Higher risk of asthma in children born by C-section than those born by vaginal delivery, particularly the children of allergic parents Protection from development of allergic illnesses may be conferred by infections and unhygienic contacts |
Decline of infections in Western countries coincides with the origin of increased incidence of autoimmune and allergic diseases Toll-like receptor stimulation can recapitulate the protective effect of infectious agents on allergy and autoimmunity Rise in reported allergy symptoms is not due to being too clean, but losing touch with “old friends” |
Clinical |
Kero et al. (2002)78
|
| Clinical |
Roduit et al. (2009)83
|
| Clinical and preclinical evidences |
von Mutius (2007)84
|
| Autoimmune diseases |
Type 1 diabetes |
Risk of diabetes increased by late preterm birth (34–36 wk) and C-section delivery Higher risk of diabetes in offspring associated with increased maternal age 20% higher risk of childhood-onset type 1 diabetes after C-section delivery (from a meta-analysis of observational studies)Autoimmunity prevented by parenteral administration of multiple TLR agonists TLR-mediated effects involve immunoregulatory cytokines such as IL-10 and transforming growth factor-beta and different subsets of regulatory T cells Increased risk of immunoglobulin E-mediated food allergy associated with C-section delivery Protection from celiac disease associated with breastfeeding Celiac disease later in life positively associated with elective, but not emergency, cesarean delivery Lower total diversity of the microbiota in C-section compared with vaginally delivered infants throughout the first 2 years of life Lower diversity of the phylum Bacteroidetes in C-section-born infants during the first 2 years of life Increased circulating levels of Th1-associated chemokines during infancy (CXCL10 and CXCL11 in blood) associated with vaginal delivery Lower proportions of regulatory T cells, tolerogenic dendritic cells, and less IL-10 gene expression in mesenteric lymph nodes and spleens of C-section-born adult mice Several chronic immune diseases associated with cesarean delivery as an early-life environmental risk factor Increased risk of inflammatory bowel disease with cesarean delivery |
Probiotics that stimulate TLRs also protect from autoimmune diseases Microbiota development in infants is affected by mode of delivery and relates |
Clinical |
Algert et al. (2009)79
|
| Clinical |
Cardwell et al. (2008)85
|
| Preclinical (mouse) |
Aumeunier et al. (2010)86
|
|
|
Clinical |
Mezoff et al. (2013)87
|
| Systematic review and meta-analysis of observational studies |
Akobeng et al. (2006)88
|
| Clinical |
Marild et al. (2012)76
|
|
Celiac disease |
|
Clinical |
Jakobsson et al. (2014)89
|
|
|
differences in colonization patterns to the maturation of a balanced Th1/Th2 immune response |
|
Preclinical (mouse) |
Hansen et al. (2014)90
|
| Clinical Systematic review and meta-analysis |
Sevelsted et al. (2015)91 Li et al. (2014)92
|
|
|
| Metabolic dysregulation |
Obesity |
|
Increased risk of childhood obesity in infants delivered by C-section, even after adjusting for maternal body mass index, birth weight, and other variables (prospective prebirth cohort study) Increased body mass in childhood and adolescence associated with cesarean delivery (longitudinal birth cohort study, following subjects up to 15 years of age) Higher numbers of bifidobacteria in fecal samples during infancy in children who remained at a normal weight than in children who became overweight Greater number of Staphylococcus aureus and microbiota aberrancy during infancy in children who became overweight than in children who were normal weight Fecal microbiota of C-section infants was dominated with Citrobacter sp., Escherichia coli, and Clostridium difficile while the most abundant bacterial species in vaginally delivered infants were Acinetobacter sp., Bifidobacterium sp., and Staphylococcus sp. Intestinal microbiota of C-section-delivered infants also characterized by an absence of Bifidobacteria species in this study75 |
Deviations in gut microbiota may predispose to energy storage and obesity; therefore, early microbial differences may predict weight later in life Aberrant compositional development of the gut microbiota precedes becoming overweight. The large load of E. coli in C-section-delivered babies in comparison with vaginally delivered counterparts again points toward the aberrant and disturbed gut microbial community structure in these infants |
Clinical (prospective prebirth cohort study) |
Huh et al. (2012)80
|
| Clinical (longitudinal birth cohort study) |
Blustein et al. (2013)81
|
| Clinical |
Kalliomaki et al. (2008)74
|
| Clinical |
Pandey et al. (2012)75
|
