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

Abstract

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–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. Results 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. Conclusions 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.

Probiotics induce intestinal IgA secretion in weanling mice potentially through promoting intestinal APRIL expression and modulating the gut microbiota composition

“…Its high aggregation in the intestine may lead to diseases such as intestinal inflammation. 50 Excessive accumulation of Mucispirillum in the intestinal tract of mice can cause colitis (mainly Crohn's disease) in mice after weaning, whereas mice are protected from colitis by breast milk IgA before weaning. 51 After intervention with Bifidobacterium , intestinal immune function could be maintained by reducing Mucispirillum abundance.…”

The Impact of Microbiota–Immunity–Hormone Interactions on Autoimmune Diseases and Infection

“…Notably, the interactions between GM and the immune system established in the first year of life can exert long-term effects on immune responses [ 12 ]. This, in turn, may play a role in determining the host’s susceptibility to infections and immune-related disorders later in life [ 13 , 14 ]. In addition, throughout life, GM affects immune functions, often with systemic outcomes that can be independent of the GM colonization site.…”

Early-life gut microbiota and neurodevelopment in preterm infants: a narrative review

“…Accumulating evidence suggests that GM plays a role in several aspects of the host central nervous system (from development to function) through direct and indirect communication with the brain along the MGBA (32)(33)(34). However, the underlying mechanisms are far from being fully elucidated.…”