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

Gut Microbiome Characteristics in feral and domesticated horses from different geographic locations

Domesticated horses live under different conditions compared with their extinct wild ancestors. While housed, medicated, and kept on a restricted source of feed, the microbiota of domesticated horses is hypothesized to be altered. We assessed the fecal microbiome of 57 domestic and feral horses from different locations on three continents, observing geographical differences. A higher abundance of Eukaryota (p p p p </p

Probiotics, gut microbiota and their influence on host health and disease

The gastrointestinal tract (GIT) of mammals hosts a high and diverse number of different microorganisms, known as intestinal microbiota. Many probiotics were originally isolated from the GIT, and they were defined by the FAO/WHO as live microorganisms which when administered in adequate amounts confer a health benefit on the host. Probiotics exert their beneficial effects on the host through four main mechanisms: interference with potential pathogens, improvement of barrier function, immunomodulation and production of neurotransmitters, and their host targets vary from the resident microbiota to cellular components of the gut-brain axis. However, in spite of the wide array of beneficial mechanisms deployed by probiotic bacteria, relatively few effects have been supported by clinical data. In this regard, different probiotic strains have been effective in Antibiotic-Associated Diarrhea or Inflammatory Bowel Disease for instance. The aim of this review was to compile the molecular mechanisms underlying the beneficial effects of probiotics, mainly through their interaction with the intestinal microbiota and with the intestinal mucosa. The specific benefits discuss in this paper include among others those elicited directly through dietary modulation of the human gut microbiota.This article is protected by copyright. All rights reservedResearch in our lab is funded by Grants AGL2013-44039R and AGL2013-44761-P from the Spanish “Plan Estatal de I+D+I.” Part of the authors is also partially funded by the [15VI013] Contract-Programme from the University of Vigo and the Agrupamento INBIOMED from DXPCTSUG-FEDER unha maneira de facer Europa (2012/273). B. S. was recipient of a Ramón y Cajal postdoctoral contract from the Spanish Ministry of Economy and Competitiveness

Preterm Delivery: Microbial Dysbiosis, Gut Inflammation and Hyperpermeability

International audiencePreterm birth is one of the main health problems encountered in the neonatal period, especially because it is also the first cause of death in the critical 1st month of life and the second in children under 5 years of age. Not only preterm birth entails short term health risks due to low weight and underdeveloped organs, but also increases the risk of suffering from non-transmissible diseases in the long term. To date, it is known that medical conditions and lifestyle factors could increase the risk of preterm birth, but the molecular mechanisms that control this process remain unclear. Luteolysis, increased inflammation or oxidative stress have been described as possible triggers for preterm birth and, in some cases, the cause of dysbiosis in preterm neonates. Several murine models have been developed to shed light into the mechanistic of preterm birth but, for the most part, are inflammation-based labor induction models and the offspring health readouts are mainly limited to survival and weight. Using a set of SWISS-CD1 mice born prematurely we analyzed inflammation and gut permeability parameters compared with term pups at weaning age. Overall, preterm mice presented higher systemic inflammation and gastrointestinal tract permeability. In this perspective article, we discuss the recent discoveries on preterm birth and the necessity of non-inflammatory murine models to really understand these phenotypes and be able to design strategies to prevent the sequels of this traumatic event in neonates

Microbial-Driven Immunological Memory and Its Potential Role in Microbiome Editing for the Prevention of Colorectal Cancer.

Over the last several years, many advances have been made in understanding the role of bacteria in the pathogenesis of gastrointestinal cancers. Beginning with Helicobacter pylori being recognized as the first bacterial carcinogen and the causative agent of most gastric cancers, more recent studies have examined the role of enteric microbes in colorectal cancer. In the digestive tract, these communities are numerous and have a complex interrelationship with local immune/inflammatory responses that impact the health of the host. As modifying the microbiome in the stomach has decreased the risk of gastric cancer, modifying the distal microbiome may decrease the risk of colorectal cancers. To date, very few studies have considered the notion that mucosal lymphocyte-dependent immune memory may confound attempts to change the microbial components in these communities. The goal of this review is to consider some of the factors impacting host-microbial interactions that affect colorectal cancer and raise questions about how immune memory responses to the local microbial consortium affect any attempt to modify the composition of the intestinal microbiome