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

Abstract

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.

Conserving the holobiont

“…Olfactory communication is extremely widespread among animals, and facilitates complex social interactions among many vertebrates (Bienenstock, Kunze, & Forsythe, 2018;Wyatt, 2014). The revelation that microbes could be essential to this process forces a rethink of many aspects of behavioural and sensory ecology (Archie & Theis, 2011;Archie & Tung, 2015;Bienenstock et al, 2018). The recognition that microbially mediated olfactory communication is an important driver of vertebrate behaviour has led to a recent call to incorporate olfaction into the microbiome-gut-brain axis (Bienenstock et al, 2018).…”

“…Microbes may influence behaviour via direct neuronal connections between the gut and the brain, via their effect on physiology (Bienenstock et al, 2018), and via their effect on animal communication, via either the gut or through scent glands . The microbial role in olfactory communication suggests we must reconsider much of what we know about signalling and information theory as it applies to this mode of animal interactions.…”

“…The revelation that microbes could be essential to this process forces a rethink of many aspects of behavioural and sensory ecology (Archie & Theis, ; Archie & Tung, ; Bienenstock et al, ). The recognition that microbially mediated olfactory communication is an important driver of vertebrate behaviour has led to a recent call to incorporate olfaction into the microbiome–gut–brain axis (Bienenstock et al, ). Microbes may influence behaviour via direct neuronal connections between the gut and the brain, via their effect on physiology (Bienenstock et al, ), and via their effect on animal communication, via either the gut or through scent glands (Carthey et al, ).…”

“…The recognition that microbially mediated olfactory communication is an important driver of vertebrate behaviour has led to a recent call to incorporate olfaction into the microbiome–gut–brain axis (Bienenstock et al, ). Microbes may influence behaviour via direct neuronal connections between the gut and the brain, via their effect on physiology (Bienenstock et al, ), and via their effect on animal communication, via either the gut or through scent glands (Carthey et al, ). The microbial role in olfactory communication suggests we must reconsider much of what we know about signalling and information theory as it applies to this mode of animal interactions.…”

Searching for the gut microbial contributing factors to social behavior in rodent models of autism spectrum disorder

“…Since then more groups have observed that in both rats and mice, VPA exposure consistently decreases sociability (Kim et al, ; Kim et al, ; Moldrich et al, ; Roullet et al, ). Additionally, VPA exposure diminishes olfactory discrimination, which can be related to social recognition and development (Bienenstock et al, ; Melo et al, ; Roullet et al, ; Terry and Johanson, ).…”