Background Most interactions between the host and its microbiota occur at the gut barrier, and primary colonizers
are essential in the gut barrier maturation in the early life. The mother–ofspring transmission of microorganisms is
the most important factor infuencing microbial colonization in mammals, and C‑section delivery (CSD) is an impor‑
tant disruptive factor of this transfer. 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
infammation. The main goal of this study is to decipher the role of the early‑life gut microbiota‑barrier alterations and
its links with later‑life risks of intestinal infammation in a murine model of CSD.
Results The higher sensitivity to chemically induced infammation 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 homeo‑
stasis. It switches the pup’s immune response to an infammatory context and alters the epithelium structure and
the mucus‑producing cells, disrupting gut homeostasis. This presence of a too diverse microbiota in the very early
life involves a disproportionate short‑chain fatty acids ratio and an excessive antigen exposure across the vulnerable
gut barrier in the frst days of life, before the gut closure. 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 infammation in ex‑germ‑free mice colonized by CSD pups’ microbiota.
Conclusions Early‑life gut microbiota‑host crosstalk alterations related to CSD could be the linchpin behind the phe‑
notypic efects that lead to increased susceptibility to an induced infammation later in life in mice.
Keywords C‑section delivery, Microbiota, Primary colonization, Early life, Infammation, Gut barrier, Murine modelinfo:eu-repo/semantics/publishedVersio
