Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system

Chevalier, G.; Siopi, Eleni; Guenin-Macé, Laure; Pascal, Maud; Laval, Thomas; Rifflet, Aline; Boneca, Ivo Gomperts; Demangel, Caroline; Colsch, Benoît; Pruvost, Alain; Chu‐Van, Emeline; Messager, Aurélie; Leulier, François; Lepousez, Gabriel; Eberl, Gérard; Lledo, Pierre−Marie

doi:10.1038/s41467-020-19931-2

Cited by 241 publications

(194 citation statements)

References 88 publications

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“…FMT of conventionally raised mice to germ-free mice induced changes in intestinal eCB levels and eCBome gene expression, strengthening the link between gut microbiota and the eCBome [98]. Moreover, FMT from mice with unpredictable mild chronic stress to naïve mice showed a transfer of depressive phenotypes that was concomitant with a decrease in eCBs and peripheral levels of fatty acids [68]. Studies relating to the relationship between diet, gut microbiota, and plasma eCBs showed correlation between several gut microbes and circulating eCBs, which was also influenced by fat mass and fatty acid intake [99,100].…”

Section: Potential Interactions Between Gut Microbiota Inflammation and Endocannabinoidome In Mental Conditionsmentioning

confidence: 79%

“…To sum up, physical activity and its impact on eCB signaling in animals produce a yet to be fully understood impact on running performance, motivation, memory, and neuroplasticity, through hippocampal CB1 signaling. CB1 could also play a role in those metabolic-driven inflammatory processes and excessive weight gain that extensively impact on neural functions [68].…”

Section: Hippocampal Endocannabinoidomementioning

confidence: 99%

“…Non-strenuous exercise and a diet full of omega-3, micronutrients, prebiotics, quality of amino acids (precursors of neurotransmitters), and fermented food would confer positive cerebral outcomes and prevent the appearance of neuropathologies [109]. The gut microbiota could be an intermediary between eCB-mediated energy balance, inflammation, and brain-related functions [68].…”

Section: Potential Interactions Between Gut Microbiota Inflammation and Endocannabinoidome In Mental Conditionsmentioning

confidence: 99%

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Neurobiological Processes Induced by Aerobic Exercise through the Endocannabinoidome

Forteza

Giorgini

Raymond

2021

Cells

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Evidence suggesting the triangulation of the endocannabinoid system, exercise, and neurological health is emerging. In addition to the endocannabinoids N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG), the expanded endocannabinoid system, known as the endocannabinoidome (eCBome), appears to be an important player in this relationship. The eCBome includes several endocannabinoid-like mediators such as N-acylethanolamines and 2-monoacylglycerols, the enzymes involved in their biosynthesis and degradation, and the receptors they affect. This review aims to relate the functional interactions between aerobic exercise, and the molecular and cellular pathways related to endocannabinoids, in the hypothalamus, hippocampus, and the periphery, with special attention given to associations with emotional state, cognition, and mental health. Given the well-documented roles of many eCBome members in regulating stress and neurological processes, we posit that the eCBome is an important effector of exercise-induced central and peripheral adaptive mechanisms that benefit mental health. Gut microbiota imbalance, affecting the gut-brain axis and metabolism, also influences certain eCBome-modulated inflammation pathways. The integrity of the gut microbiota could thus be crucial in the onset of neuroinflammation and mental conditions. Further studies on how the modulation by exercise of the peripheral eCBome affects brain functions could reveal to be key elements in the prevention and treatment of neuropsychological disorders.

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Section: Potential Interactions Between Gut Microbiota Inflammation and Endocannabinoidome In Mental Conditionsmentioning

confidence: 79%

Section: Hippocampal Endocannabinoidomementioning

confidence: 99%

Section: Potential Interactions Between Gut Microbiota Inflammation and Endocannabinoidome In Mental Conditionsmentioning

confidence: 99%

See 1 more Smart Citation

Neurobiological Processes Induced by Aerobic Exercise through the Endocannabinoidome

Forteza

Giorgini

Raymond

2021

Cells

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“…Interestingly, Bercik et al (2011) have shown that transferring fecal content from an innately stress-sensitive mouse to non-anxious mice is sufficient to elicit anxiety-like reactions (i.e., reduced exploratory behavior) in the receiver animal. Correspondingly, the reverse pattern, that is, transferring portions of GM from non-anxious mice to innately anxious mice induces the latter to manifest reduced anxiety (for an analogous result, see also the more recent Chevalier et al 2020).…”

Section: The Mgb Axis and Emotional Processingmentioning

confidence: 95%

Out of our skull, in our skin: the Microbiota-Gut-Brain axis and the Extended Cognition Thesis

2021

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According to a shared functionalist view in philosophy of mind, a cognitive system, and cognitive function thereof, is based on the components of the organism it is realized by which, indeed, play a causal role in regulating our cognitive processes. This led philosophers to suggest also that, thus, cognition could be seen as an extended process, whose vehicle can extend not only outside the brain but also beyond bodily boundaries, on different kinds of devices. This is what we call the ‘Externally Extended Cognition Thesis.’ This notion has generated a lively debate. Here, we offer a novel notion of extended cognition, according to which cognition can be seen as being realized (and expanded) outside the brain, but still inside the body. This is what we call the ‘Internally Extended Cognition Thesis’. Not only our thesis but also our approach while defending it is innovative. The argument we offer is supported by recent empirical findings in the life sciences and biomedicine, which suggest that the gut microbiota’s activity has a functional role in regulating our cognitive processes and behaviors. In doing so, we embrace the holobiont-perspective, according to which it is possible to claim that what we call biological individuals are not autonomous entities with clear boundaries, but should rather be seen as networks of multiple interactions among species. Thus, by analyzing different sets of evidence in light of the holobiont-perspective, we argue that the gut microbiota could be seen as a component of our organism. On the basis of the philosophical interpretation of this evidence, however, we also suggest that there are no impediments standing the way of considering the gut microbiota also as a functional extension of our cognitive system. If so, this amounts to extending cognition out of ‘our skull’, though still confining it within ‘our body’: to ‘our gut’. This is an instance of the ‘Internally Extended Cognition Thesis,’ whose benefits for an original (biologically informed) theory of extended cognition are discussed.

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“…Whether modifications in microbiota composition impact brain function remains elusive although the involvement of immune (proinflammatory cytokines), neural (spinal and vagus nerves), metabolic (short-chain fatty acids), endocrine and neurotransmitter pathways have been suggested 2 . A recent study 8 provided mechanistic evidence suggesting that stress, diet and gut microbiota generate a pathological feedforward loop that contributes to depressive disorders via the central endocannabinoid system. However, such a loop has not been demonstrated for other disorders that can be induced by stress, for instance cognitive alterations.…”

Section: Introductionmentioning

confidence: 99%

Microbiota and stress: a loop that impacts memory

Kraïmi

Lormant

Calandreau

et al. 2021

Preprint

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Chronic stress and the gut microbiota appear to comprise a feed-forward loop, which contributes to the development of depressive disorders. Evidence suggests that memory can also be impaired by either chronic stress or microbiota imbalance. However, it remains to be established whether these could be a part of an integrated loop model and be responsible for memory impairments. To shed light on this, we used a two-pronged approach in Japanese quail: first stress-induced alterations in gut microbiota were characterized, then we tested whether this altered microbiota could affect brain and memory function when transferred to a germ-free host. The cecal microbiota of chronically stressed quails was found to be significantly different from that of unstressed individuals with lower α and β diversities and increased Bacteroidetes abundance largely represented by the Alistipes genus, a well-known stress target in rodents and humans. The transfer of this altered microbiota into germ-free quails decreased their spatial and cue-based memory abilities as previously demonstrated in the stressed donors. The recipients also displayed increased anxiety-like behavior, reduced basal plasma corticosterone levels and differential gene expression in the brain. Furthermore, cecal microbiota transfer from a chronically stressed individual was sufficient to mimic the adverse impact of chronic stress on memory in recipient hosts and this action may be related to the Alistipes genus. Our results provide evidence of a feed-forward loop system linking the microbiota-gut-brain axis to stress and memory function and suggest that maintaining a healthy microbiota could help alleviate memory impairments linked to chronic stress.

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Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system

Cited by 241 publications

References 88 publications

Neurobiological Processes Induced by Aerobic Exercise through the Endocannabinoidome

Neurobiological Processes Induced by Aerobic Exercise through the Endocannabinoidome

Out of our skull, in our skin: the Microbiota-Gut-Brain axis and the Extended Cognition Thesis

Microbiota and stress: a loop that impacts memory

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