Moody microbes or fecal phrenology: what do we know about the microbiota-gut-brain axis?

Forsythe, Paul; Kunze, Wolfgang; Bienenstock, John

doi:10.1186/s12916-016-0604-8

Cited by 136 publications

(119 citation statements)

References 124 publications

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“…However, the impact of intestinal dysbiosis induced by early-life AB exposure on brain function and behaviour remains unknown. Increasing evidence indicates that intestinal bacteria might communicate with the brain to induce changes in behaviour and neurochemistry141516. While germ-free models or administration of high doses of AB in animals have revealed behavioural and cognitive alterations associated with dysbiosis2223242526, they have unclear clinical relevance.…”

Section: Discussionmentioning

confidence: 99%

“…There is now mounting evidence, in humans and rodents, for the role of specific microbial compositions in modulating brain function including behaviour14151617. Complete absence of intestinal bacteria (in germ-free mice) results in modification of blood–brain barrier (BBB) permeability18, impaired immune response of the microglia19, increased myelination20, hyperactivity of the hypothalamus–pituitary–adrenal axis21, changes in brain neurochemistry22 and decreased anxiety and social behaviours2223.…”

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confidence: 99%

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Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior

et al. 2017

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There is increasing concern about potential long-term effects of antibiotics on children's health. Epidemiological studies have revealed that early-life antibiotic exposure can increase the risk of developing immune and metabolic diseases, and rodent studies have shown that administration of high doses of antibiotics has long-term effects on brain neurochemistry and behaviour. Here we investigate whether low-dose penicillin in late pregnancy and early postnatal life induces long-term effects in the offspring of mice. We find that penicillin has lasting effects in both sexes on gut microbiota, increases cytokine expression in frontal cortex, modifies blood–brain barrier integrity and alters behaviour. The antibiotic-treated mice exhibit impaired anxiety-like and social behaviours, and display aggression. Concurrent supplementation with Lactobacillus rhamnosus JB-1 prevents some of these alterations. These results warrant further studies on the potential role of early-life antibiotic use in the development of neuropsychiatric disorders, and the possible attenuation of these by beneficial bacteria.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior

et al. 2017

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“…However, a recent systematic review of psychiatric benefits of probiotics in humans found little evidence of positive outcomes [121], a finding running counter to the general optimism. Others have stated that the field, though not ‘faecal phrenology’, will ultimately be unable to provide true translational value without rigorous elucidation of mechanisms [122]. Numerous limitations must both constrain enthusiasm and stimulate further investigations.…”

Section: Future Directions and Psychobiotics Beyond Prebiotics And Prmentioning

confidence: 99%

Psychobiotics and the Manipulation of Bacteria–Gut–Brain Signals

Sarkar

Lehto

Harty

et al. 2016

Trends in Neurosciences

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Psychobiotics were previously defined as live bacteria (probiotics) which, when ingested, confer mental health benefits through interactions with commensal gut bacteria. We expand this definition to encompass prebiotics, which enhance the growth of beneficial gut bacteria. We review probiotic and prebiotic effects on emotional, cognitive, systemic, and neural variables relevant to health and disease. We discuss gut–brain signalling mechanisms enabling psychobiotic effects, such as metabolite production. Overall, knowledge of how the microbiome responds to exogenous influence remains limited. We tabulate several important research questions and issues, exploration of which will generate both mechanistic insights and facilitate future psychobiotic development. We suggest the definition of psychobiotics be expanded beyond probiotics and prebiotics to include other means of influencing the microbiome.

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“…Nevertheless, the study of the gut microbiome in normal populations around the world, and in various human diseases and models thereof, has led to the establishment of possible causal associations between imbalances of the microbiome and disease. These have ranged from metabolic conditions such as obesity and diabetes, to liver disease, irritable bowel syndrome (IBS), neurodegenerative disorders and various psychiatric conditions (Cani et al, 2008;Collins, Surette & Bercik, 2012;Cryan & Dinan, 2012;Forsythe & Kunze, 2013;Collins, 2014;Mayer, Padua & Tillisch, 2014;Bienenstock, Kunze & Forsythe, 2015;Forsythe, Kunze & Bienenstock, 2016;Tilg, Cani & Mayer, 2016). These studies have in turn pointed to very complex relationships between different microbial communities and the endocrine, immune and nervous systems, which because of their complexity, have previously been ignored or at the very least, inadequately explored.…”

Section: Introductionmentioning

confidence: 99%

Disruptive physiology: olfaction and the microbiome–gut–brain axis

2017

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This review covers the field of olfaction and chemosensation of odorants and puts this information into the context of interactions between microbes and behaviour; the microbiome-gut-brain axis (MGBA). Recent emphasis has also been placed on the concept of the holobiome which states that no single aspect of an organism should be viewed separately and thus must include examination of their associated microbial populations and their influence. While it is known that the microbiome may be involved in the modulation of animal behaviour, there has been little systematized effort to incorporate into such studies the rapidly developing knowledge of the wide range of olfactory systems. The classical olfactory system is evolutionarily conserved in multiple taxa from insects through to fish, reptiles and mammals, and is represented by the largest gene families in vertebrates. Mice have over 1000 different olfactory receptors and humans about 400. They are distributed throughout the body and are even found in spermatozoa where they function in chemotaxis. Each olfactory receptor has the unique functional capability of high-affinity binding to several different molecular ligands. These and other properties render the cataloguing of odorants (odorome) with specific actions a difficult task. Some ectopic olfactory receptors have been shown to have functional effects in the gut and kidney, highlighting the complexity of the systems engaged by odorants. However, there are, in addition to classical olfactory receptors, at least two other families of receptors involved in olfaction that are also widely found expressed on tissues in many different organs in addition to the nervous system and brain: the trace-amine associated and formyl peptide receptors. Bacteria can make many if not most odorants and are responsible for recognition of species and relative relatedness, as well as predator presence, among many other examples. Activation of different combinations of olfactory receptors by bacterial products such as β-phenylethylamine have been shown even to control expression of emotions such as fear and aggression. The number of examples of bacterial products and volatile odorants influencing brain function and behaviour is expanding rapidly. Since it is recognized that many different bacterial products and metabolites also function as social cues, and may themselves be directly or indirectly causative of behavioural change, it becomes ever more important to include olfaction into studies of the MGBA. Clearly there are broader implications for the involvement of olfaction in this rapidly evolving field. These include improvement in our understanding of the pathways engaged in various behaviours, and the identification of novel approaches and new targets in efforts to modulate behavioural changes.

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Moody microbes or fecal phrenology: what do we know about the microbiota-gut-brain axis?

Cited by 136 publications

References 124 publications

Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior

Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior

Psychobiotics and the Manipulation of Bacteria–Gut–Brain Signals

Disruptive physiology: olfaction and the microbiome–gut–brain axis

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