Evidence map›Paper›PMID 26912607›Full record

ReviewThe international journal of neuropsychopharmacology2016

Growing up in a Bubble: Using Germ-Free Animals to Assess the Influence of the Gut Microbiota on Brain and Behavior.

Pauline Luczynski, Karen-Anne McVey Neufeld, Clara Seira Oriach, Gerard Clarke, Timothy G Dinan, John F Cryan

Registry-linked trialOpen access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in The international journal of neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03494725 (Proof-of-Concept "Stress & Anxiety Dampening Effects of Lpc-37"), which is not on this map. Cited by 313 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
313citing papers in PubMed, 6 pooled it
27.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03494725 nacompletednot on this mapstarted 2018, after this paper: background citation

Proof-of-Concept "Stress & Anxiety Dampening Effects of Lpc-37"

TypeinterventionalSponsorDaacroRan2018 to 2018Enrolled120ConditionsHealthy, Stress, PsychologicalArmsLpc-37, Placebo
3 · Its place in the literature

Who cites it

313 citing papers in PubMed, 6 syntheses or guidelines pooled it, 611 citations in OpenAlex.

  1. Pooled it
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  13. Humanizing Zophobas morio larvae microbiota for rapid screening of emerging decolonization strategies against multidrug-resistant bacteria.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026
    Article
  14. Review
  15. Article
  16. Review
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  18. Article
  19. Humans as an extended phenotype of their microbiota.Theory in biosciences = Theorie in den Biowissenschaften · 2026
    Article
  20. Article

253 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Pauline LuczynskiAPC Microbiome Institute (Ms Luczynski, Dr McVey Neufeld, Ms Oriach, Dr Clarke, Dr Dinan, and Dr Cryan), Department of Psychiatry and Neurobehavioral Science (Ms Oriach, Dr Clarke, and Dr Dinan), and Department of Anatomy and Neuroscience (Dr Cryan), University College Cork, Cork, Ireland.
Karen-Anne McVey NeufeldAPC Microbiome Institute (Ms Luczynski, Dr McVey Neufeld, Ms Oriach, Dr Clarke, Dr Dinan, and Dr Cryan), Department of Psychiatry and Neurobehavioral Science (Ms Oriach, Dr Clarke, and Dr Dinan), and Department of Anatomy and Neuroscience (Dr Cryan), University College Cork, Cork, Ireland.
Clara Seira OriachAPC Microbiome Institute (Ms Luczynski, Dr McVey Neufeld, Ms Oriach, Dr Clarke, Dr Dinan, and Dr Cryan), Department of Psychiatry and Neurobehavioral Science (Ms Oriach, Dr Clarke, and Dr Dinan), and Department of Anatomy and Neuroscience (Dr Cryan), University College Cork, Cork, Ireland.
Gerard ClarkeAPC Microbiome Institute (Ms Luczynski, Dr McVey Neufeld, Ms Oriach, Dr Clarke, Dr Dinan, and Dr Cryan), Department of Psychiatry and Neurobehavioral Science (Ms Oriach, Dr Clarke, and Dr Dinan), and Department of Anatomy and Neuroscience (Dr Cryan), University College Cork, Cork, Ireland.
Timothy G DinanAPC Microbiome Institute (Ms Luczynski, Dr McVey Neufeld, Ms Oriach, Dr Clarke, Dr Dinan, and Dr Cryan), Department of Psychiatry and Neurobehavioral Science (Ms Oriach, Dr Clarke, and Dr Dinan), and Department of Anatomy and Neuroscience (Dr Cryan), University College Cork, Cork, Ireland.
John F CryanAPC Microbiome Institute (Ms Luczynski, Dr McVey Neufeld, Ms Oriach, Dr Clarke, Dr Dinan, and Dr Cryan), Department of Psychiatry and Neurobehavioral Science (Ms Oriach, Dr Clarke, and Dr Dinan), and Department of Anatomy and Neuroscience (Dr Cryan), University College Cork, Cork, Ireland. J.Cryan@ucc.ie.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

There is a growing recognition of the importance of the commensal intestinal microbiota in the development and later function of the central nervous system. Research using germ-free mice (mice raised without any exposure to microorganisms) has provided some of the most persuasive evidence for a role of these bacteria in gut-brain signalling. Key findings show that the microbiota is necessary for normal stress responsivity, anxiety-like behaviors, sociability, and cognition. Furthermore, the microbiota maintains central nervous system homeostasis by regulating immune function and blood brain barrier integrity. Studies have also found that the gut microbiota influences neurotransmitter, synaptic, and neurotrophic signalling systems and neurogenesis. The principle advantage of the germ-free mouse model is in proof-of-principle studies and that a complete microbiota or defined consortiums of bacteria can be introduced at various developmental time points. However, a germ-free upbringing can induce permanent neurodevelopmental deficits that may deem the model unsuitable for specific scientific queries that do not involve early-life microbial deficiency. As such, alternatives and complementary strategies to the germ-free model are warranted and include antibiotic treatment to create microbiota-deficient animals at distinct time points across the lifespan. Increasing our understanding of the impact of the gut microbiota on brain and behavior has the potential to inform novel management strategies for stress-related gastrointestinal and neuropsychiatric disorders.

Indexed as

AnimalsBehavior, AnimalBrainGastrointestinal MicrobiomeGerm-Free Lifecognitive dysfunctiongerm-free mousemicrobiota-gut-brain axissocial developmentstress response

Identifiers

PMID26912607
PMCPMC5006193
OpenAlexW2283710302

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.