title: Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects.
abstract: BACKGROUND
  Preclinical studies have identified certain probiotics as psychobiotics - live microorganisms with a potential mental health benefit. Lactobacillus rhamnosus (JB-1) has been shown to reduce stress-related behaviour, corticosterone release and alter central expression of GABA receptors in an anxious mouse strain. However, it is unclear if this single putative psychobiotic strain has psychotropic activity in humans. Consequently, we aimed to examine if these promising preclinical findings could be translated to healthy human volunteers.
  
  
  OBJECTIVE
  To determine the impact of L. rhamnosus on stress-related behaviours, physiology, inflammatory response, cognitive performance and brain activity patterns in healthy male participants.
  
  
  METHODS
  An 8week, randomized, placebo-controlled, cross-over design was employed. Twenty-nine healthy male volunteers participated. Participants completed self-report stress measures, cognitive assessments and resting electroencephalography (EEG). Plasma IL10, IL1β, IL6, IL8 and TNFα levels and whole blood Toll-like 4 (TLR-4) agonist-induced cytokine release were determined by multiplex ELISA. Salivary cortisol was determined by ELISA and subjective stress measures were assessed before, during and after a socially evaluated cold pressor test (SECPT).
  
  
  RESULTS
  There was no overall effect of probiotic treatment on measures of mood, anxiety, stress or sleep quality and no significant effect of probiotic over placebo on subjective stress measures, or the HPA response to the SECPT. Visuospatial memory performance, attention switching, rapid visual information processing, emotion recognition and associated EEG measures did not show improvement over placebo. No significant anti-inflammatory effects were seen as assessed by basal and stimulated cytokine levels.
  
  
  CONCLUSIONS
  L. rhamnosus was not superior to placebo in modifying stress-related measures, HPA response, inflammation or cognitive performance in healthy male participants. These findings highlight the challenges associated with moving promising preclinical studies, conducted in an anxious mouse strain, to healthy human participants. Future interventional studies investigating the effect of this psychobiotic in populations with stress-related disorders are required.
authors.affiliation: APC Microbiome Institute, University College Cork, Ireland; Department of Psychiatry and Neurobehavioral Science, University College Cork, Ireland.
authors.forename: John R
authors.initials: JR
authors.lastname: Kelly
authors.affiliation: APC Microbiome Institute, University College Cork, Ireland; Department of Psychiatry and Neurobehavioral Science, University College Cork, Ireland.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Allen
authors.affiliation: Department of Electrical and Electronic Engineering, University College Cork, Ireland.
authors.forename: Andriy
authors.initials: A
authors.lastname: Temko
authors.affiliation: INFANT Research Centre and Department of Pediatrics & Child Health, University College Cork, Ireland.
authors.forename: William
authors.initials: W
authors.lastname: Hutch
authors.affiliation: APC Microbiome Institute, University College Cork, Ireland.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kennedy
authors.affiliation: Department of Psychiatry and Neurobehavioral Science, University College Cork, Ireland.
authors.forename: Niloufar
authors.initials: N
authors.lastname: Farid
authors.affiliation: Alimentary Health Ltd., Cork Airport Business Park, Cork, Ireland.
authors.forename: Eileen
authors.initials: E
authors.lastname: Murphy
authors.affiliation: INFANT Research Centre and Department of Pediatrics & Child Health, University College Cork, Ireland.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Boylan
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Bienenstock
authors.affiliation: APC Microbiome Institute, University College Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Ireland.
authors.forename: John F
authors.initials: JF
authors.lastname: Cryan
authors.affiliation: APC Microbiome Institute, University College Cork, Ireland; Department of Psychiatry and Neurobehavioral Science, University College Cork, Ireland.
authors.forename: Gerard
authors.initials: G
authors.lastname: Clarke
authors.affiliation: APC Microbiome Institute, University College Cork, Ireland; Department of Psychiatry and Neurobehavioral Science, University College Cork, Ireland. Electronic address: t.dinan@ucc.ie.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Dinan
mesh_terms: D000328:Adult; D001288:Attention / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D004569:Electroencephalography; D064368:Healthy Volunteers; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D052201:Lacticaseibacillus rhamnosus; D008297:Male; D009483:Neuropsychological Tests; D019936:Probiotics / Q000008:administration & dosage* / Q000627:therapeutic use; D012463:Saliva / Q000737:chemistry; D013315:Stress, Psychological / Q000188:drug therapy* / Q000523:psychology; D055815:Young Adult
chemical_list: D016207:Cytokines; D006854:Hydrocortisone
keywords: Brain-gut axis; Cognition; EEG; Memory; Psychobiotic; Stress