From Short- to Long-Term Effects of C-Section Delivery on Microbiome Establishment and Host Health

Abstract

The establishment of gut microbiota has been proven to be impacted by several factors during pregnancy, delivery, and neonate periods. The body of evidence describing C-section delivery (CSD) as one of the most disruptive events during early life has expanded in recent years, concluding that CSD results in a drastic change in microbiota establishment patterns. When comparing the gut microbiota composition of CSD babies with vaginally delivered (VD) babies, the former show a microbiome that closely resembles that found in the environment and the mother’s skin, while VD babies show a microbiome more similar to the vaginal microbiome. Although these alterations of normal gut microbiota establishment tend to disappear during the first months of life, they still affect host health in the mid–long term since CSD has been correlated with a higher risk of early life infections and non-transmissible diseases, such as inflammatory diseases, allergies, and metabolic diseases. In recent years, this phenomenon has also been studied in other mammals, shedding light on the mechanisms involved in the effects of a CSD on host health. In addition, strategies to revert the disruptions in gut microbiomes caused by a CSD are currently in the process of development and evaluation. In this review, we discuss the recent advances in CSD research, from the alteration of gut microbiota establishment to the possible effects on host health during early life and development.

Neonatal Programming of Microbiota Composition: A Plausible Idea That Is Not Supported by the Evidence

“…In this regard, various epidemiological studies have established statistical associations between early alteration of the intestinal microbiota and the subsequent occurrence of particular pathophysiologies (reviewed by Blottière et al, 2013;Tamburini et al, 2016;Milani et al, 2017;Stinson, 2020). It has been documented in particular in the case of birth by CS (Korpela, 2021;Ríos-Covian et al, 2021) and perinatal antibiotic therapies (Azad et al, 2017;Aires, 2021), but these associations should be viewed with caution due to the possibility of biases relating to reverse causalities and the fact that the repercussions of CS are not limited to modulation of the microbiota (King, 2021). Interventional studies on animal models are more convincing in this respect; to date, several studies have demonstrated associations between early microbiotal perturbations and subsequent physiological consequences (e.g., Cox et al, 2014or Pocheron et al, 2021, demonstrating the need to consider early microbiota alterations in the DOHAD process.…”

“…It is also important to keep in mind that the evolution of the microbiota takes place at the same time as the intestinal maturation process, which affects both the immune and epithelial components of the colon, both of which are involved in the control of bacteria engraftment (Biol-N'garagba and Louisot, 2003;Zhang et al, 2015). As intestinal maturation can be reversibly influenced by the presence of bacteria (for reviews, see Ríos-Covian et al, 2021;Sarkar et al, 2021), its modulation by early settlers may -beyond constituting mechanisms for the possible role of early microbiota perturbations as a relay for later physiological consequences (not discussed here) -as well contribute to priority effects. Note that the maturation of these two tissues is otherwise paramount for the microbiome differences associated with newborn gestational age.…”

“…Specifically, the microbiota could contribute to DOHaD either as a relay: changes in the microbiota induced by the neonatal environment would affect its ability to interact with tissue and organ development during the critical windows of neonatal life with lasting consequences, or as a memory link between early environment and adult health: the initial bacterial configuration would shape the composition of the microbiome for life and therefore program its contribution to the regulation of host physiology. The first option has been the subject of several recent reviews (Stinson, 2020;Ríos-Covian et al, 2021, Sarkar et al, 2021 and will therefore be out of our scope. Conversely, the widely propagated assumption that early modifications of the neonatal microbiome program the microbiome throughout the entire life remains actually to be established.…”

The Role of Nutritional Factors in the Modulation of the Composition of the Gut Microbiota in People with Autoimmune Diabetes

“…It has also been shown that meconium from full-term newborns is not sterile and that the bacteria present in it are also present in the amniotic fluid, vagina, and oral cavity [11]. Colonization also occurs at the time of childbirth: in the case of natural birth, the gastrointestinal tract of the newborn contains bacteria that live in the gastrointestinal tract and vagina of the mother, while in newborns born by caesarean section, the bacterial flora contains bacteria inhabiting the mother's skin, so they have a smaller number of bacteria of the type Bifidobacterium and Bacteroides and more pathogenic Enterococcus, Enterobacter, and Klebsiella [26,27]. Following delivery, the diet is one of the main factors that modulates the gut microbiota of infants.…”

Physicians’ Understanding of the Role of the Microbiome in Allergies and Asthma: A Questionnaire-Based Study in Saudi Arabia

“… 8 , 9 Loss of these early-life microbial contacts, often caused by antibiotic misuse or cesarean section birth, can trigger an imbalance between the microbiota and a loss of microbial diversity, known as dysbiosis, and immunological aberrations that predispose children to allergies and asthma. 5 , 10 , 11 Conversely, restoring this microbial imbalance via therapeutic applications of probiotics, which are nutritional supplements containing health-promoting microbes, has yielded promising results in the management of allergy and asthma symptoms. 12 These promising scientific observations together with clinical evidence may reveal a previously unexplored role of the microbiome in immune-mediated diseases.…”