Gut barrier-microbiota imbalances in early life lead to higher sensitivity to inflammation in a murine model of C-section delivery

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

Gut barrier-microbiota imbalances in early life lead to higher sensitivity to inflammation in a murine model of C-section delivery

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-offspring transmission of microorganisms is the most important factor influencing microbial colonization in mammals, and C-section delivery (CSD) is an important 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 inflammation. 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 inflammation in a murine model of CSD. The higher sensitivity to chemically induced 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 pup's immune response to an inflammatory 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 first 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 inflammation in ex-germ-free mice colonized by CSD pups' microbiota. Early-life gut microbiota-host crosstalk alterations related to CSD could be the linchpin behind the phenotypic effects that lead to increased susceptibility to an induced inflammation later in life in mice

A novel hypomorphic Apex1 mouse model implicates apurinic-apyrimidinic endonuclease 1 in oxidative DNA damage repair in gastric epithelial cells.

While best known for its role in oxidative DNA damage repair, apurinic-apyrimidinic endonuclease-1 (APE1) is a multifunctional protein that regulates multiple host responses during oxidative stress including the reductive activation of transcription factors. As knockout of the APE1-encoding gene, Apex1, is embryonically lethal, we sought to create a viable model with generalized inhibition of APE1 expression