The resident prokaryotic microbiota of the metazoan gut elicits profound effects on the growth and development of the intestine. However, the molecular mechanisms of symbiotic prokaryotic–eukaryotic ...cross‐talk in the gut are largely unknown. It is increasingly recognized that physiologically generated reactive oxygen species (ROS) function as signalling secondary messengers that influence cellular proliferation and differentiation in a variety of biological systems. Here, we report that commensal bacteria, particularly members of the genus Lactobacillus, can stimulate NADPH oxidase 1 (Nox1)‐dependent ROS generation and consequent cellular proliferation in intestinal stem cells upon initial ingestion into the murine or Drosophila intestine. Our data identify and highlight a highly conserved mechanism that symbiotic microorganisms utilize in eukaryotic growth and development. Additionally, the work suggests that specific redox‐mediated functions may be assigned to specific bacterial taxa and may contribute to the identification of microbes with probiotic potential.
Non‐pathogenic gut bacteria promote ROS generation in host epithelial cells, thereby regulating intestinal homeostasis in both mammals and insects.
Introduction
Public health responses often lack the infrastructure to capture the impact of public health emergencies on pregnant women and infants, with limited mechanisms for linking pregnant women ...with their infants nationally to monitor long-term effects. In 2019, the Centers for Disease Control and Prevention (CDC), in close collaboration with state, local, and territorial health departments, began a 5-year initiative to establish population-based mother–baby linked longitudinal surveillance, the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET).
Objectives
The objective of this report is to describe an expanded surveillance approach that leverages and modernizes existing surveillance systems to address the impact of emerging health threats during pregnancy on pregnant women and their infants.
Methods
Mother–baby pairs are identified through prospective identification during pregnancy and/or identification of an infant with retrospective linking to maternal information. All data are obtained from existing data sources (e.g., electronic medical records, vital statistics, laboratory reports, and health department investigations and case reporting).
Results
Variables were selected for inclusion to address key surveillance questions proposed by CDC and health department subject matter experts. General variables include maternal demographics and health history, pregnancy and infant outcomes, maternal and infant laboratory results, and child health outcomes up to the second birthday. Exposure-specific modular variables are included for hepatitis C, syphilis, and Coronavirus Disease 2019 (COVID-19). The system is structured into four relational datasets (maternal, pregnancy outcomes and birth, infant/child follow-up, and laboratory testing).
Discussion
SET-NET provides a population-based mother–baby linked longitudinal surveillance approach and has already demonstrated rapid adaptation to COVID-19. This innovative approach leverages existing data sources and rapidly collects data and informs clinical guidance and practice. These data can help to reduce exposure risk and adverse outcomes among pregnant women and their infants, direct public health action, and strengthen public health systems.
Abstract only
A growing body of data has emerged showing that members of the gut microbiota are essential for the normal physiology and homeostasis of the intestine. However, the molecular basis for ...these processes are not well understood. In this study, we describe a novel role for the commensal bacterium
Lactobacillus
in intestinal cytoprotection. We show that this bacterial genus specifically induces cellular reactive oxygen species (ROS) in both
Drosophila
and murine guts. This ROS induction in turn stimulates the redox‐sensitive Nrf2 pathway and leads to consequent ARE (Antioxidant Response Element)‐dependent cytoprotective gene expression. Nrf2/ARE pathway mediated cytoprotection is well established in many tissues, but its stimulation by gut bacteria is completely unrecognized. Using Nrf2 knockout
Drosophila
and mice, we demonstrate that Nrf2 is required for protection against a variety of intestinal insults. Together, these data show that gut microbial stimulated ROS generation modulates the Nrf2 signaling pathway thus maintaining intestinal epithelial homeostasis and cytoprotection, and that this effect is evolutionarily conserved.
Abstract only
A growing body of data has emerged showing that gut commensal bacteria are essential for normal mucosal physiology and reparative function. However, the molecular bases for these ...symbiotic processes are not well understood. In this study we describe a novel role for gut commensal microbiota in protecting against xenobiotic insult. Compared to germ‐free flies, conventional (raised with normal microbiota) and conventionalized (colonized with known commensals)
Drosophila
are protected from gut‐directed injury. After conventionalization, we detected microbial‐induced cellular reactive oxygen species (ROS) in the gut followed by Nrf2 pathway activation and consequent ARE (Antioxidant Response Element)‐dependent cytoprotective gene expression. Nrf2/ARE pathway‐dependent cytoprotection is well established in many tissues, but stimulation by gut bacteria is completely unrecognized. In addition, conventionalized germ‐free animals exhibit higher tonic levels of redox‐responsive genes which may function to maintain the basal cytoprotective response within the mucosa. These results are consistent with recent studies suggesting that bacterial‐host crosstalk is mediated in part by the rapid cellular generation of ROS. Together, these data show that gut microbial‐dependent ROS generation modulates the Nrf2 signaling pathway thus maintaining intestinal epithelial homeostasis and cytoprotection.
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