Beneficial effect of GABA-rich fermented milk on insomnia involving regulation of gut microbiota

Yu, Leilei; Han, Xiao; Cen, Shi; Duan, Hui; Feng, Saisai; Xue, Yuzheng; Tian, Fengwei; Zhao, Jianxin; Zhang, Hao; Zhai, Qixiao; Chen, Wei

doi:10.1016/j.micres.2020.126409

Cited by 84 publications

(45 citation statements)

References 44 publications

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“…This complex system is in the process of being understood: while produced GABA may serve as additional carbon source for some gut commensal bacteria (Strandwitz et al, 2019) and act as signaling molecule between bacteria (Dagorn et al, 2013), it may also interact with the vast amounts of GABA receptors present in the GIT (Seifi and Swinny, 2019;Zhao et al, 2020) and stimulate the immune system (Zhao et al, 2020). This may explain the positive effects of GABA-enriched foods in attenuating anxiety and insomnia (Yu et al, 2020), and the correlation between bacterially-derived GABA and/or GAD-system genes in mental health, such as reported for autism (Kang et al, 2018;Averina et al, 2020) and depression (Zheng et al, 2016;Strandwitz et al, 2019;Valles-Colomer et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

GABA Production by Human Intestinal Bacteroides spp.: Prevalence, Regulation, and Role in Acid Stress Tolerance

et al. 2021

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The high neuroactive potential of metabolites produced by gut microbes has gained traction over the last few years, with metagenomic-based studies suggesting an important role of microbiota-derived γ-aminobutyric acid (GABA) in modulating mental health. Emerging evidence has revealed the presence of the glutamate decarboxylase (GAD)-encoding gene, a key enzyme to produce GABA, in the prominent human intestinal genus Bacteroides. Here, we investigated GABA production by Bacteroides in culture and metabolic assays combined with comparative genomics and phylogenetics. A total of 961 Bacteroides genomes were analyzed in silico and 17 metabolically and genetically diverse human intestinal isolates representing 11 species were screened in vitro. Using the model organism Bacteroides thetaiotaomicron DSM 2079, we determined GABA production kinetics, its impact on milieu pH, and we assessed its role in mitigating acid-induced cellular damage. We showed that the GAD-system consists of at least four highly conserved genes encoding a GAD, a glutaminase, a glutamate/GABA antiporter, and a potassium channel. We demonstrated a high prevalence of the GAD-system among Bacteroides with 90% of all Bacteroides genomes (96% in human gut isolates only) harboring all genes of the GAD-system and 16 intestinal Bacteroides strains producing GABA in vitro (ranging from 0.09 to 60.84 mM). We identified glutamate and glutamine as precursors of GABA production, showed that the production is regulated by pH, and that the GAD-system acts as a protective mechanism against acid stress in Bacteroides, mitigating cell death and preserving metabolic activity. Our data also indicate that the GAD-system might represent the only amino acid-dependent acid tolerance system in Bacteroides. Altogether, our results suggest an important contribution of Bacteroides in the regulation of the GABAergic system in the human gut.

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Section: Discussionmentioning

confidence: 99%

GABA Production by Human Intestinal Bacteroides spp.: Prevalence, Regulation, and Role in Acid Stress Tolerance

et al. 2021

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“…Future work that specifically focuses on SCFAs would also support the growing body of existing preclinical and emerging human data (Boehme et al, 2019; Burokas et al, 2017; Dalile et al, 2019; Lee et al, 2020). More specifically, preclinical work suggests a link between Ruminococcus- induced increases in SCFAs and improvements in anxiety-related behaviours (Yu et al, 2020), and stress and emotional instability (Provensi et al, 2019). However, important to note is that clinical translation of this work has yielded conflicting results.…”

Section: Discussionmentioning

confidence: 99%

Microbiota links to neural dynamics supporting threat processing

Hall

Harrison

Iyer

et al. 2021

Preprint

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There is growing recognition that the composition of the gut microbiota influences behaviour, including responses to threat. The cognitive-interoceptive appraisal of threat-related stimuli relies on dynamic neural computations between the anterior insular (AIC) and the dorsal anterior cingulate (dACC) cortices. If, to what extent, and how microbial consortia influence the activity of this cortical threat processing circuitry is unclear. We addressed this question by combining a threat processing task, neuroimaging, 16S rRNA profiling, and computational modelling in healthy participants. Results showed interactions between high-level ecological indices with threat-related AIC-dACC neural dynamics. At finer taxonomic resolutions, the abundance of Ruminococcus was differentially linked to connectivity between, and activity within the AIC and dACC during threat updating. Functional inference analysis provides a strong rationale to motivate future investigations of microbiota-derived metabolites in the observed relationship with threat-related brain processes.

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“…Depletion in either of these neurotransmitters contributes to the development of various neuropsychiatric disorders including depression. Most antidepressants work by restoring the levels of monoamine neurotransmitters (i.e., 5-HT, DA and NE) [115][116][117][118]. The gut microbiota is involved in the modulation of neurotransmitters via either neural, humoral or immune-mediated pathways.…”

Section: Inflammationmentioning

confidence: 99%

“…In its sequential study, probiotics Lactobacillus plantarum and Bifidobacterium adolescentis, which were ascertained as the most efficient GABA-producers with anti-depressive potential, improved depressive behavior in mice models with an efficacy comparable to fluoxetine [90]. Studies have shown that the administration of Lactobacillus brevis, one of the main GABA-producers among Lactobacillus species, significantly improved insomnia in mice models and mediated anti-depressive effects, comparable to fluoxetine [89,91,92,116].…”

Section: Inflammationmentioning

confidence: 99%

Exploring the Role and Potential of Probiotics in the Field of Mental Health: Major Depressive Disorder

et al. 2021

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The field of probiotic has been exponentially expanding over the recent decades with a more therapeutic-centered research. Probiotics mediated microbiota modulation within the microbiota–gut–brain axis (MGBA) have been proven to be beneficial in various health domains through pre-clinical and clinical studies. In the context of mental health, although probiotic research is still in its infancy stage, the promising role and potential of probiotics in various mental disorders demonstrated via in-vivo and in-vitro studies have laid a strong foundation for translating preclinical models to humans. The exploration of the therapeutic role and potential of probiotics in major depressive disorder (MDD) is an extremely noteworthy field of research. The possible etio-pathological mechanisms of depression involving inflammation, neurotransmitters, the hypothalamic–pituitary–adrenal (HPA) axis and epigenetic mechanisms potentially benefit from probiotic intervention. Probiotics, both as an adjunct to antidepressants or a stand-alone intervention, have a beneficial role and potential in mitigating anti-depressive effects, and confers some advantages compared to conventional treatments of depression using anti-depressants.

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Beneficial effect of GABA-rich fermented milk on insomnia involving regulation of gut microbiota

Cited by 84 publications

References 44 publications

GABA Production by Human Intestinal Bacteroides spp.: Prevalence, Regulation, and Role in Acid Stress Tolerance

GABA Production by Human Intestinal Bacteroides spp.: Prevalence, Regulation, and Role in Acid Stress Tolerance

Microbiota links to neural dynamics supporting threat processing

Exploring the Role and Potential of Probiotics in the Field of Mental Health: Major Depressive Disorder

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