How do probiotics and prebiotics function at distant sites?

The realisation that microbes regarded as beneficial to the host can impart effects at sites distant from their habitat, has raised many possibilities for treatment of diseases. The objective of a workshop hosted in Turku, Finland, by the International Scientific Association for Probiotics and Prebiotics, was to assess the evidence for these effects and the extent to which early life microbiome programming influences how the gut microbiota communicates with distant sites. In addition, we examined how probiotics and prebiotics might affect the skin, airways, heart, brain and metabolism. The growing levels of scientific and clinical evidence showing how microbes influence the physiology of many body sites, leads us to call for more funding to advance a potentially exciting avenue for novel therapies for many chronic diseases.

Bifidobacteria modulate cognitive processes in an anxious mouse strain.

Increasing evidence suggests that a brain-gut-microbiome axis exists, which has the potential to play a major role in modulating behaviour. However, the role of this axis in cognition remains relatively unexplored. Probiotics, which are commensal bacteria offering potential health benefit, have been shown to decrease anxiety, depression and visceral pain-related behaviours. In this study, we investigate the potential of two Bifidobacteria strains to modulate cognitive processes and visceral pain sensitivity. Adult male BALB/c mice were fed daily for 11 weeks with B. longum 1714, B. breve 1205 or vehicle treatment. Starting at week 4, animals were behaviourally assessed in a battery of tests relevant to different aspects of cognition, as well as locomotor activity and visceral pain. In the object recognition test, B. longum 1714-fed mice discriminated between the two objects faster than all other groups and B. breve 1205-fed mice discriminated faster than vehicle animals. In the Barnes maze, B. longum 1714-treated mice made fewer errors than other groups, suggesting a better learning. In the fear conditioning, B. longum 1714-treated group also showed better learning and memory, yet presenting the same extinction learning profile as controls. None of the treatments affected visceral sensitivity. Altogether, these data suggest that B. longum 1714 had a positive impact on cognition and also that the effects of individual Bifidobacteria strains do not generalise across the species. Clinical validation of the effects of probiotics on cognition is now warranted.

Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice.

BACKGROUND: Accumulating evidence suggests that commensal bacteria consumption has the potential to have a positive impact on stress-related psychiatric disorders. However, the specific bacteria influencing behaviors related to anxiety and depression remain unclear. To this end, we compared the effects of two different Bifidobacteria on anxiety and depression-like behavior; an antidepressant was also used as a comparator. METHODS: Innately anxious BALB/c mice received daily Bifidobacterium longum (B.) 1714, B. breve 1205, the antidepressant escitalopram or vehicle treatment for 6 weeks. Behavior was assessed in stress-induced hyperthermia test, marble burying, elevated plus maze, open field, tail suspension test, and forced swim test. Physiological responses to acute stress were also assessed. KEY RESULTS: Both Bifidobacteria and escitalopram reduced anxiety in the marble burying test; however, only B. longum 1714 decreased stress-induced hyperthermia. B. breve 1205 induced lower anxiety in the elevated plus maze whereas B. longum 1714 induced antidepressant-like behavior in the tail suspension test. However, there was no difference in corticosterone levels between groups. CONCLUSIONS & INFERENCES: These data show that these two Bifidobacteria strains reduced anxiety in an anxious mouse strain. These results also suggest that each bacterial strain has intrinsic effects and may be beneficially specific for a given disorder. These findings strengthen the role of gut microbiota supplementation as psychobiotic-based strategies for stress-related brain-gut axis disorders, opening new avenues in the field of neurogastroenterology.

Disturbance of the gut microbiota in early-life selectively affects visceral pain in adulthood without impacting cognitive or anxiety-related behaviors in male rats.

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.

Increased sensitivity to the effects of chronic social defeat stress in an innately anxious mouse strain.

Stress and genetic predisposition are two of the major risk factors for a variety of psychiatric illnesses. Inbred mouse strains are considered useful tools in dissecting the genetic basis of complex disorders. Indeed, mice of the C57BL/6 and BALB/c strains, differing markedly in anxiety behaviours, are among the most widely used in psychopharmacological research. However, there is a paucity of studies investigating the impact of social stress in these two strains. Moreover, whether these two mouse strains exhibit different sensitivities to chronic social defeat stress remains poorly studied. Thus in this study we compared the impact of repeated (10 days) social defeat stress on a variety of behavioural and endocrine parameters including social interaction, locomotor activity, plasma corticosterone, body weight and stress-related physiological parameters in both mouse strains. Given that the duration of stress exposure may differentially affect such responses we also compared stressors of short (Social Defeat-Short; SD-S) and of long (Social Defeat-Long; SD-L) duration. Our results show that although mice from both strains were defeated in both social defeat paradigms, only BALB/c mice displayed social interaction impairments following SD-S, whereas both strains were behaviourally sensitive to SD-L. Moreover, both strains also differed in some of the physiological alterations induced by social defeat stress. Specifically, SD-S did not induce any change in corticosterone levels in either of the two strains, whereas SD-L was able to induce significant changes in C57BL/6 mice only. SD-S induced differential effects on bodyweight gain in both strains, increasing it in C57BL/6 and decreasing it in BALB/c mice, whereas SD-L had no effect. On the other hand, exposure to SD-S resulted in cardiac hypertrophy in C57BL/6 mice and SD-L induced spleen hypertrophy and thymus atrophy in BALB/c mice in addition to decreasing faecal output. Overall, the innately anxious BALB/c mice were more sensitive to social stress than C57BL/6, with differential behavioural and physiological alterations emerging as a function of stress severity. These data suggest different coping strategies to social interaction stress between the two mouse strains. The genetic basis of this stress-resilience/susceptibility warrants further investigation.