Involvement of the microbiota-gut-brain axis in chronic restraint stress: disturbances of the kynurenine metabolic pathway in both the gut and brain

Deng, Yuanyuan; Zhou, Manfei; Wang, Junfeng; Yao, Jiaxi; Yu, Jing; Liu, Wenwei; Wu, Linlin; Gao, Rong

doi:10.1080/19490976.2020.1869501

“…Moreover, METH abuse exhibited depressive symptoms with a wide range of severity 35 . The decreased level of tryptophan was closely associated with depression; our recent study indicated a significant decrease in tryptophan and an increase in a toxic metabolite, kynurenine, in chronic restraint stress‐induced depression in mice 36 . The disturbance of the metabolism of these important amino acids was also consistent with those found in experiments related to animal metabonomics 23,37 .…”

Section: Discussionsupporting

confidence: 75%

Untargeted metabolomics analysis by gas chromatography/time‐of‐flight mass spectrometry of human serum from methamphetamine abusers

Wang

¹

,

Xu

²

,

Xu

³

et al. 2021

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Methamphetamine (METH) abuse has become a global public health problem. However, the potential mechanisms involving METH‐induced metabolic disorders have thus far remained poorly understood. Metabolomics can provide a clue for the cause of apparent changes and consequently be used to investigate the METH‐induced dysregulation of metabolite expression and the mechanism of metabolic disorder mechanism. This laboratory investigation included 80 METH abusers and 80 healthy people. The serum metabolites were detected and analysed by gas chromatography/time‐of‐flight mass spectrometry. Raw data were processed with the software MS DIAL, which includes deconvolution, peak alignment and compound identification. The data matrix was processed by univariate and multivariate analyses for significant metabolite screening with the criteria of variable importance in projection values > 1, fold change > 1.5 and the t test (p value < 0.05). Significant differences in 16 metabolites (deoxycholic acid, cholic acid, hydroxylamine, etc.) in serum were found between the METH abuse group and the control group. Energy metabolic pathways and several amino acid metabolic pathways (alanine, aspartic acid and glutamate metabolism and tryptophan metabolism) were primarily involved. Further analysis indicated that the area under the receiver operating characteristic curve (AUC) was 0.998 for these 16 metabolites. Among the metabolites, three carbohydrates (d‐ribose, cellobiose and maltotriose) had an AUC of 0.975, which were determined as potential markers of abuse. We observed metabolic disturbances in METH abusers, particularly perturbation in energy metabolism and amino acid metabolism, which can provide new insights into the search for biomarkers and the mechanisms underlying the adverse effects of METH on human health.

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“…Since the link between the serotonergic system and HPA axis is well-recognized now 66 , the alterations of behavior and HPA axis activity found in our study could be explained by the high abundance of Alistipes species and their action on the Trp pathway. In addition, our results on the tryptophanase function in the gut microbiota are in line with several studies showing a link between Trp metabolism in the gut and behavioral changes during chronic stress [67][68][69] . These findings in Alistipes make this bacterial genus an important candidate in the interaction between .…”

Section: Discussionsupporting

confidence: 92%

Microbiota and stress: a loop that impacts memory

Kraïmi

¹

,

Lormant

²

,

Calandreau

³

et al. 2021

Preprint

0

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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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“…Since the link between the serotonergic system and HPA axis is well-recognized now (O'Mahony et al, 2015), the alterations of behavior and HPA axis activity found in our study could be explained by the high abundance of Alistipes species and their action on the Trp pathway. In addition, our results on the tryptophanase function in the gut microbiota are in line with several studies showing a link between Trp metabolism in the gut and behavioral changes during chronic stress (Deng et al, 2021;Mir et al, 2020). These findings in Alistipes make this bacterial genus an important candidate in the interaction between the gut microbiota and the stress system and corroborate the implication of microbial Trp metabolism in behavioral and neurological stress-induced changes.…”

Section: Discussionsupporting

confidence: 91%

Microbiota and stress: a loop that impacts memory

Kraïmi

¹

,

Lormant

²

,

Calandreau

³

et al. 2022

Psychoneuroendocrinology

View full text Add to dashboard Cite

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.

show abstract

Involvement of the microbiota-gut-brain axis in chronic restraint stress: disturbances of the kynurenine metabolic pathway in both the gut and brain

Cited by 178 publications

References 52 publications

Untargeted metabolomics analysis by gas chromatography/time‐of‐flight mass spectrometry of human serum from methamphetamine abusers

Untargeted metabolomics analysis by gas chromatography/time‐of‐flight mass spectrometry of human serum from methamphetamine abusers

Microbiota and stress: a loop that impacts memory

Microbiota and stress: a loop that impacts memory

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