Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects.

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. OBJECTIVES: 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, IL1ß, 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.

Three-dimensional tonotopic organization of the C57 mouse cochlear nucleus.

The cochlear nucleus (CN) is the first sound processing center in the central auditory system that receives the almost unprocessed auditory information from the auditory periphery. The functional organization of the CN has been studied to a great extent in many mammals, including the cat, rat and bat. Yet, despite the general usefulness of the mouse, including the availability of various inbred strains and gene-manipulated lines, our current understanding of the mouse CN remains limited. The purpose of this study was to illustrate the functional organization of the CN in C57 mice, using an electrophysiological approach. Our results showed that the auditory response properties of CN neurons were similar in all three of the CN subdivisions. Sound frequency was systematically represented in each of the three CN subdivisions, i.e., the anteroventral, posteroventral and the dorsal divisions. The best frequency of CN neurons decreased along the dorsomedial-to-ventrolateral axis in an orderly progression whereas the tonotopic axes were relatively indistinct in the rostrocaudal plane. There was no disruption of the tonotopic map within each subdivision of the CN. The findings indicate that the CN tonotopic organization in the C57 mouse is similar to that in the cat and other mammals.