Review Article Ann Nutr Metab 2018;73(suppl 3):12–16 Birth Mode-Related Differences in Gut Microbiota Colonization and Immune System Development M. Pilar Francino a, b a Unitat Mixta d’Investigació en Genòmica i Salut, Fundació per al Foment de la Investigació Sanitària i Biomèdica de la Comunitat Valenciana (FISABIO-Salut Pública)/Institut de Biologia Integrativa de Sistemes (Universitat de València), València, Spain; b CIBER en Epidemiología y Salud Pública, Madrid, Spain Published online: July 24, 2018 M. Pilar Francino Unitat Mixta d’Investigació en Genòmica i Salut FISABIO-Salut Pública Avda. Catalunya 21, ES–46020 València (Spain) E-Mail francino_pil @gva.es © 2018 S. Karger AG, Basel E-Mail karger@karger.com www.karger.com/anm DOI: 10.1159/000490842 Keywords C-section · Neonate · Gut microbiota · Immune system · Tolerance · Allergy Abstract Background: The process of early gut colonization is ex- tremely variable among individuals and is influenced by nu- merous factors. Among these, the mode of birth will strong- ly shape the early microbial exposure and immune environ- ment of the neonate. Summary: Here, I review how the concomitant processes of microbiota and immune system development are altered by C-section delivery and the ef- fects of such alterations on long-term health. Key messages: C-section delivery impinges on microbiota and immune sys- tem development through various means: (i) if labor is lack- ing, intrauterine immune responses dependent on this pro- cess will not occur, affecting the immune environment of the neonate; (ii) the lack of exposure to the vaginal and fecal mi- crobes of the mother will alter the type and diversity of the microbes that colonize the gut at birth; (iii) the different starting points in terms of microbial exposure and immune environment will mark the course of microbiota and im- mune system development during the first months of life, generating multiple feedbacks between these 2 processes. Given that the first months of life represent a crucial time window in the ontogenesis of the immune system and the establishment of tolerance, C-section delivery will impact on the lifelong risk of developing immune disease. © 2018 S. Karger AG, Basel Immunological Effects of the Lack of Labor The type of birth is known to influence the immune environment of the neonate, as labor induces immune responses within the uterine cavity that will be absent in the case of elective C-sections [1]. Intra-uterine concen- trations of inflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor-α (TNF-α) are elevated during the normal course of term labor [2–4]. These cytokines play an important role during delivery, as they stimulate prostaglandin biosynthesis, thereby in- ducing myometrium contractility and ripening of the