C-section delivery induces gut barrier-microbiota imbalances in early life and leads to higher sensitivity to inflammation

Abstract

Abstract Background The mother-newborn transmission of microorganisms is the most important factor influencing microbial colonization in the neonate, and C-section delivery (CSD) is an important disruptive factor of this transfer. Although this medical procedure saves countless lives, it may also have costs. Recently, the deregulation of symbiotic host-microbe interactions in early life has been shown to alter the maturation of the immune system, predisposing the host to gut barrier dysfunction and inflammation. The main goal of this study is to decipher the role of CSD in the early-life gut microbiota-barrier alterations and its links with later-life risks of intestinal inflammation. Results The higher sensitivity to inflammation in CSD mice is related to excessive exposure to a too diverse microbiota too early in life. This early microbial stimulus has short-term consequences on the host homeostasis. It switches the newborn immune response to an inflammatory context and alters the epithelium structure and the mucus-producing cells, disrupting gut homeostasis. This "too much too early" principle involves a disproportionate short-chain fatty acids ratio and an excessive antigen exposure across the vulnerable gut barrier in the first days of life. Besides, as shown by microbiota transfer experiments, the microbiota is causal in the high sensitivity of CSD mice to chemical-induced colitis and in most of the phenotypical parameters found altered in early life. Finally, supplementation with Lactobacilli, the main bacterial group impacted by CSD in mice, reverts the higher sensitivity to inflammation in ex germ-free mice colonised by CSD pups’ microbiota. Conclusions Early life gut microbiota-host crosstalk alterations related to CSD could be the linchpin behind the phenotypic effects that lead to increased disease susceptibility later in life.