The DOI matches its Crossref record; 105 of the 106 references it cites were found in a registry or an index.
Disturbance of the gut microbiota in early-life selectively affects visceral pain in adulthood without impacting cognitive or anxiety-related behaviors in male rats
Abstract
Disruption of bacterial colonization during the early postnatal period is increasingly being linked to adverse health outcomes. Indeed, there is a growing appreciation that the gut microbiota plays a role in neurodevelopment. However, there is a paucity of information on the consequences of early-life manipulations of the gut microbiota on behavior. To this end we administered an antibiotic (vancomycin) from postnatal days 4-13 to male rat pups and assessed behavioral and physiological measures across all aspects of the brain-gut axis. In addition, we sought to confirm and expand the effects of early-life antibiotic treatment using a different antibiotic strategy (a cocktail of pimaricin, bacitracin, neomycin; orally) during the same time period in both female and male rat pups. Vancomycin significantly altered the microbiota, which was restored to control levels by 8 weeks of age. Notably, vancomycin-treated animals displayed visceral hypersensitivity in adulthood without any significant effect on anxiety responses as assessed in the elevated plus maze or open field tests. Moreover, cognitive performance in the Morris water maze was not affected by early-life dysbiosis. Immune and stress-related physiological responses were equally unaffected. The early-life antibiotic-induced visceral hypersensitivity was also observed in male rats given the antibiotic cocktail. Both treatments did not alter visceral pain perception in female rats. Changes in visceral pain perception in males were paralleled by distinct decreases in the transient receptor potential cation channel subfamily V member 1, the α-2A adrenergic receptor and cholecystokinin B receptor. In conclusion, a temporary disruption of the gut microbiota in early-life results in very specific and long-lasting changes in visceral sensitivity in male rats, a hallmark of stress-related functional disorders of the brain-gut axis such as irritable bowel disorder.
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“Fourthly, preclinical studies with antibiotic administration, either in early life (O'Mahony et al., 2014) or adulthood (Verdu et al., 2008), have shown long-lasting effects on brain, spinal cord, and the ENS.”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as O'Mahony et al., 2014
In the citing paper
“While chronic antibiotic treatment impaired spatial memory in the Morris Water Maze in adult rats (Hoban et al., 2016a;Wang et al., 2015) acute treatments did not affect this type of memory when administered in early life in rats (O'Mahony et al., 2014), nor when administered during adulthood in mice and tested in the Barnes maze (Frohlich et al., 2016).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as O'Mahony et al., 2014
In the citing paper
“Disruption of the gut microbiota in early-life also has been associated with longterm changes in visceral sensitivity, emphasizing the importance of the gut microbiome in neurodevelopment of pain pathways68.”
From The gut Microbiome in adult and pediatric functional gastrointestinal disorders (2019) · cites this paper as [68]
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Metadata
- Authors
- O’Mahony, S. M., Felice, V. D., Nally, K., Savignac, H. M., Claesson, M. J., Scully, P., Woznicki, J., Hyland, N. P., Shanahan, F., Quigley, E. M., Marchesi, J. R., O’Toole, P. W., Dinan, T. G., & Cryan, J. F.
- Affiliations
- University College Cork (IE)
- ORCID
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 277
- Pages
- 885-901
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2055122111
- Cited by
- 272
- References
- 106
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 24 · 2023: 15 · 2022: 18 · 2021: 42 · 2020: 24 · 2019: 26 · 2018: 23 · 2017: 25 · 2016: 34 · 2015: 16 · 2014: 5
- FWCI
- 10.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- Science Foundation Ireland (02/CE/B124, 07/CE/B1368)
- GlaxoSmithKline
- European Community’s Seventh Framework Programme (FP7/2007-2013)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Keywords
- gut microbiota, early-life antibiotic exposure, vancomycin, visceral hypersensitivity, visceral pain, gut-brain axis, brain development, anxiety-like behavior, cognitive performance, sex differences, TRPV1, alpha2A-adrenergic receptor, cholecystokinin B receptor, irritable bowel syndrome
- MeSH terms
- Animals, Animals, Newborn, Anti-Bacterial Agents, Anxiety, Bacitracin, Behavior, Animal, Cognition, Female, Hyperalgesia, Male, Neomycin, Natamycin, Vancomycin, Rats, Sprague-Dawley, Gastrointestinal Tract, Visceral Pain, Microbiota
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