Treating Generational Stress: Effect of Paternal Stress on Development of Memory and Extinction in Offspring Is Reversed by Probiotic Treatment
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Early-life adversity is a potent risk factor for mental-health disorders in exposed individuals, and effects of adversity are exhibited across generations. Such adversities are also associated with poor gastrointestinal outcomes. In addition, emerging evidence suggests that microbiota-gut-brain interactions may mediate the effects of early-life stress on psychological dysfunction. In the present study, we administered an early-life stressor (i.e., maternal separation) to infant male rats, and we investigated the effects of this stressor on conditioned aversive reactions in the rats' subsequent infant male offspring. We demonstrated, for the first time, longer-lasting aversive associations and greater relapse after extinction in the offspring (F1 generation) of rats exposed to maternal separation (F0 generation), compared with the offspring of rats not exposed to maternal separation. These generational effects were reversed by probiotic supplementation, which was effective as both an active treatment when administered to infant F1 rats and as a prophylactic when administered to F0 fathers before conception (i.e., in fathers' infancy). These findings have high clinical relevance in the identification of early-emerging putative risk phenotypes across generations and of potential therapies to ameliorate such generational effects.
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Administration of a probiotic formulation containing L. rhamnosus R0011 and L. helveticus R0052 prevents the effects of early-life stress on fear behavior and its supporting neural network during development.
“Finally, administration of a probiotic formulation containing L. rhamnosus R0011 and L. helveticus R0052 has been shown to prevent the effects of early-life stress on fear behavior and its supporting neural network during development (Callaghan et al., 2016;Cowan et al., 2016).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Callaghan et al., 2016
The Probiotic Treatment section identifies the formulation as L. rhamnosus R0011 and L. helveticus R0052. The results section reports that treatment prevented or reversed stress-associated changes in fear-memory retention and extinction in infant rats. The paper does not show that treatment prevented effects on the supporting neural network; the Discussion treats effects on neural circuits as a possible mechanism, not a measured result. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredEarly probiotic interventions mitigate the effects of antibiotic-treated and C-section delivered infants, early-life stress, maternal high-fat diet, and maternal immune activation on infant outcomes.
“Several groups have now shown that early probiotic interventions mitigate the effects of antibiotic-treated and C-section delivered infants, early-life stress, maternal high-fat diet, and maternal immune activation on infant outcomes (see Table 5) (Buffington et al., 2016;Callaghan et al., 2016;Cowan et al., 2016;Fukui et al., 2018;Gareau et al., 2007;Hsiao et al., 2013;Korpela et al., 2018).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Callaghan et al., 2016
The high-fear phenotype is passed down the male line for at least two generations.
“a profile that is passed down the male line for at least two generations (i.e., the grand-offspring of the stressed males exhibit the same high-fear phenotype despite never directly experiencing stress) (Callaghan et al., 2016).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Callaghan et al., 2016
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Self-citation
- Authors
- Callaghan, B. L., Cowan, C. S. M., & Richardson, R.
- Affiliations
- The University of Melbourne (AU)
- UNSW Sydney (AU)
- Corresponding author
- Callaghan, Bridget L.
- Venue
- Psychological Science
- Publisher
- SAGE Publications
- Published
- 2016-07-19
- Volume
- 27
- Issue
- 9
- Pages
- 1171-1180
- ISSN
- 0956-7976 (ISSN-L)
- 1467-9280
- OpenAlex
- W2469737398
- Cited by
- 55
- References
- 12
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 4 · 2020: 7 · 2019: 10 · 2018: 6 · 2017: 6 · 2016: 2
- FWCI
- 5.11
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Psychological Science (publishedVersion)
- PubMed (publishedVersion)
- Cork Open Research Archive (University College Cork, Ireland) (submittedVersion)
- UNSWorks (UNSW Sydney) (submittedVersion, cc-by-nc-nd)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- Funders
- University of New South Wales
- Petre Foundation
- Medical Research Council
- Australian Research Council (DP120104925, DP0985554)
- National Health and Medical Research Council (APP1031688)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- childhood adversity, maternal separation, probiotic supplementation, microbiota-gut-brain axis, risk phenotypes
- MeSH terms
- Amnesia, Animals, Brain, Female, Humans, Male, Maternal Deprivation, Memory, Stress, Psychological, Wills, Cohort Effect, Rats, Sprague-Dawley, Probiotics, Rats
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