Abnormal intestinal microbial colonization in prenatally stressed offspring is related to lung and intestinal

Audrey F Duff1,2, Michael T Bailey1,2,3

  • 1Center for Microbe and Immunity Research, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States.

Insights

Prenatal stress (PNS) alters the early-life microbiome, impacting offspring immune development. These changes correlate with increased respiratory infections and are dependent on the MyD88 pathway.

Area of Science:

  • Immunology
  • Microbiology
  • Developmental Biology

Background:

  • Prenatal stress (PNS) negatively affects child health, increasing susceptibility to early-life infections like respiratory infections.
  • Maternal microbiome alterations during pregnancy due to stress are a key factor linking in utero stress to abnormal offspring development and microbial colonization.

Purpose of the Study:

  • To investigate the relationship between early-life intestinal microbial perturbations and intestinal/lung cytokine gene expression in a mouse model of PNS.
  • To characterize basal cytokine differences in relation to intestinal microbial composition in PNS-exposed offspring.

Main Methods:

  • A mouse model of prenatal stress (PNS) was utilized.
  • Intestinal microbiome composition, diversity, and differential abundance were assessed.
  • Intestinal and lung tissue gene expression, specifically focusing on cytokines, was analyzed over the first five weeks of life.
  • Experiments included MyD88 knockout mice to assess pathway dependency.

Main Results:

  • PNS offspring showed significant alterations in microbiome diversity and composition.
  • Increased interferon and proinflammatory cytokine gene signatures were observed in the ileum and lung of PNS offspring.
  • PNS-associated microbiome changes correlated with ileal and lung gene expression.
  • MyD88 knockout offspring did not exhibit PNS-associated cytokine differences.

Conclusions:

  • PNS-induced early-life microbiome changes are linked to immune development in the gut and lungs.
  • Microbe-immune interactions influenced by PNS are dependent on the MyD88 signaling pathway.
Abstract

Related Concept Videos

Development of Human Microbiota01:30

Development of Human Microbiota

The human microbiota begins developing at birth and undergoes continual change as we age. Infancy marks a critical period of microbial sensitivity, offering a “window of opportunity” during which beneficial microbes help mature the immune system. By age three, children typically develop a more stable and diverse microbial community. Newborns acquire microbes from their immediate environment; vaginal delivery favors maternal vaginal microbes, while cesarean births favor microbes from...
60
Gut-Brain Axis01:22

Gut-Brain Axis

The gut–brain axis is a bidirectional communication system that connects the gastrointestinal tract and the brain. This interaction is mediated through multiple pathways, including the vagus nerve, hormonal signals, immune responses, and chemical messengers produced by gut microbes.Microbial Contributions to Brain FunctionGut microbiota contributes significantly to brain function by producing neuroactive compounds. These include neuroactive compounds that influence neurotransmitters such...
207
Development of the Oral Microbiota01:28

Development of the Oral Microbiota

The establishment of the oral microbiome begins before birth, challenging the long-held belief that the fetal oral cavity is sterile. The presence of oral microbes such as Streptococcus and Fusobacterium in amniotic fluid suggests that microbial exposure may occur in utero, potentially through translocation from the maternal oral or gastrointestinal tract. This early colonization primes the neonatal immune system and sets the stage for subsequent microbial succession. Maternal health,...
62
Inflammatory Bowel Disease III: Crohn's Disease01:25

Inflammatory Bowel Disease III: Crohn's Disease

Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...
29
Anatomy of the Intestines01:23

Anatomy of the Intestines

Although digestion of proteins, carbohydrates, and lipids may begin in the stomach, it is completed in the intestine. The absorption of nutrients, water, and electrolytes from food and drink also occurs in the intestine. The intestines can be divided into two structurally distinct organs—the small and large intestines.
Small Intestines
The small intestine is an ~7 meter-long tube with an inner diameter of just 2.5 cm. Since most nutrients are absorbed here, the inner lining of the...
65.0K
Microbiota of the Respiratory Tract01:29

Microbiota of the Respiratory Tract

The human respiratory tract, comprising the upper and lower segments, serves as a critical interface with the external environment. The upper respiratory tract (URT)—including the nostrils, sinuses, pharynx, and oropharynx—is heavily colonized by microbes, while the lower respiratory tract (LRT), composed of the larynx, trachea, bronchi, and lungs, was long thought to be sterile. However, recent molecular studies have revealed that the lungs are not devoid of microbes but act more...
54