Related Experiment Video
Updated: Nov 10, 2025
Non-Invasive Model of Neuropathogenic Escherichia coli Infection in the Neonatal Rat
Published on: October 29, 2014
Neonatal Enteropathogenic Escherichia coli Infection Disrupts Microbiota-Gut-Brain Axis Signaling
Carly Hennessey1, Ciara E Keogh1, Mariana Barboza1
1Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
Insights
Early-life infections with enteropathogenic Escherichia coli (EPEC) in mice impair the microbiota-gut-brain axis, leading to cognitive deficits and gut inflammation in adulthood. This highlights the long-term impact of infant diarrheal diseases.
Area of Science:
- Microbiology
- Neuroscience
- Gastroenterology
- Developmental Biology
Background:
- Diarrheal diseases are a major cause of mortality in young children globally.
- Early-life infections can lead to developmental issues, including cognitive deficits, potentially via the microbiota-gut-brain (MGB) axis.
- The long-term consequences of neonatal enteric pathogen exposure on the MGB axis are not fully understood.
Purpose of the Study:
- To investigate the long-term effects of neonatal enteropathogenic Escherichia coli (EPEC) infection on the MGB axis in a mouse model.
- To assess behavioral, neurological, intestinal, and microbiota changes following early-life EPEC exposure.
Main Methods:
- Neonatal C57BL/6 mice were infected with EPEC (strain e2348/69) or a type III secretion system (T3SS) mutant via orogastric gavage at postnatal day 7.
- Adult offspring were evaluated using behavioral tests (NOR, L/D box, OFT), intestinal physiology assessments (Ussing chambers, FITC-dextran flux), and gut microbiota analysis (16S rRNA sequencing).
- Neurogenesis and neuroinflammation markers (Ki67, doublecortin, Iba1) and cytokine/receptor expression (Tnfα, Il12, Il6, Nod1/2, Tlr2/4) were measured.
Main Results:
- Neonatal EPEC infection, but not the T3SS mutant, induced ileal inflammation and impaired adult recognition memory.
- Cognitive deficits were associated with increased adult neurogenesis, neuroinflammation (microglia activation), and altered intestinal physiology (increased secretory state and permeability).
- EPEC infection led to significant gut microbiota dysbiosis, characterized by a decrease in Firmicutes, and increased expression of pro-inflammatory markers in the ileum and colon.
Conclusions:
- Neonatal infection with pathogenic EPEC has lasting detrimental effects on the microbiota-gut-brain axis into adulthood.
- Early-life enteric infections can impair cognitive function and alter gut and brain physiology, underscoring the importance of preventing diarrheal diseases in infancy.
- These findings highlight a critical window in early life where microbial insults can permanently affect neurodevelopment and gut health.
Abstract:
Diarrheal diseases are a leading cause of death in children under the age of 5 years worldwide. Repeated early-life exposures to diarrheal pathogens can result in comorbidities including stunted growth and cognitive deficits, suggesting an impairment in the microbiota-gut-brain (MGB) axis. Neonatal C57BL/6 mice were infected with enteropathogenic Escherichia coli (EPEC) (strain e2348/69; ΔescV [type III secretion system {T3SS} mutant]) or the vehicle (Luria-Bertani [LB] broth) via orogastric gavage at postnatal day 7 (P7). Behavior (novel-object recognition [NOR] task, light/dark [L/D] box, and open-field test [OFT]), intestinal physiology (Ussing chambers), and the gut microbiota (16S Illumina sequencing) were assessed in adulthood (6 to 8 weeks of age). Neonatal infection of mice with EPEC, but not the T3SS mutant, caused ileal inflammation in neonates and impaired recognition memory (NOR task) in adulthood. Cognitive impairments were coupled with increased neurogenesis (Ki67 and doublecortin immunostaining) and neuroinflammation (increased microglia activation [Iba1]) in adulthood. Intestinal pathophysiology in adult mice was characterized by increased secretory state (short-circuit current [Isc]) and permeability (conductance) (fluorescein isothiocyanate [FITC]-dextran flux) in the ileum and colon of neonatally EPEC-infected mice, along with increased expression of proinflammatory cytokines (Tnfα, Il12, and Il6) and pattern recognition receptors (Nod1/2 and Tlr2/4). Finally, neonatal EPEC infection caused significant dysbiosis of the gut microbiota, including decreased Firmicutes, in adulthood. Together, these findings demonstrate that infection in early life can significantly impair the MGB axis in adulthood.
Related Concept Videos
01:23Anatomy of the 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...
01:05Physiology of Enteric Nervous System and Gut Health