Exploration of microbiota targets for major depressive disorder and mood related traits

Chung, Yu-Chu Ella; Chen, Hsi‐Chung; Chou, Hsiang‐Chin Lori; Chen, I‐Ming; Lee, Meei-Shyuan; Chuang, Li-Chung; Liu, Yen-Wenn; Lu, Mong Liang; Chen, Chun-Hsin; Wu, Chia-Fang; Huang, Ming‐Chyi; Liao, Shih‐Cheng; Ni, Yen‐Hsuan; Lai, Mei‐Shu; Shih, Wei-Liang; Kuo, Po-Hsiu

doi:10.1016/j.jpsychires.2019.01.016

Cited by 119 publications

(162 citation statements)

References 45 publications

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“…Patients with major depressive disorder demonstrate increased amounts of Blautia spp. amongst other bacterial changes 59,60 . Taken together, developmental exposure of California mice to BPA or GEN may result in what might be considered a signature stress "microbiome" profile.…”

Section: Discussionmentioning

confidence: 99%

Developmental exposure of California mice to endocrine disrupting chemicals and potential effects on the microbiome-gut-brain axis at adulthood

Kaur

Sarma

Marshall

et al. 2020

Sci Rep

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Xenoestrogens are chemicals found in plant products, such as genistein (GEN), and in industrial chemicals, e.g., bisphenol A (BPA), present in plastics and other products that are prevalent in the environment. Early exposure to such endocrine disrupting chemicals (EDC) may affect brain development by directly disrupting neural programming and/or through the microbiome-gut-brain axis. To test this hypothesis, California mice (Peromyscus californicus) offspring were exposed through the maternal diet to GEN (250 mg/kg feed weight) or BPA (5 mg/kg feed weight, low dose-LD or 50 mg/kg, upper dose-UD), and dams were placed on these diets two weeks prior to breeding, throughout gestation, and lactation. Various behaviors, gut microbiota, and fecal metabolome were assessed at 90 days of age. The LD but not UD of BPA exposure resulted in individuals spending more time engaging in repetitive behaviors. GEN exposed individuals were more likely to exhibit such behaviors and showed socio-communicative disturbances. BPA and GEN exposed females had increased number of metabolites involved in carbohydrate metabolism and synthesis. Males exposed to BPA or GEN showed alterations in lysine degradation and phenylalanine and tyrosine metabolism. Current findings indicate cause for concern that developmental exposure to BPA or GEN might affect the microbiome-gut-brain axis. Many fetuses and infants are exposed to xenoestrogens, such as bisphenol A (BPA) and genistein (GEN), through the placenta and milk 1-4. Infants that are fed soy-based diets may also be directly exposed to phytoestrogens,

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Section: Discussionmentioning

confidence: 99%

Developmental exposure of California mice to endocrine disrupting chemicals and potential effects on the microbiome-gut-brain axis at adulthood

Kaur

Sarma

Marshall

et al. 2020

Sci Rep

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“…Our correlation analysis showed that there was a positive correlation between white matter integrity and the relative abundance of Holdemania and Eubacterium. These bacteria are both known to be changed in abundances in other disorders: Holdemania is increased in individuals with MDD [67][68][69], and Eubacterium is decreased in children with ASD [70]. However, to our knowledge, this is the first study that found significant correlations between these bacteria and brain structural and functional changes.…”

Section: Discussionmentioning

confidence: 76%

Gut microbiota from persons with attention-deficit/hyperactivity disorder affects the brain in mice

Tengeler¹,

Dam

Wiesmann³

et al. 2020

Microbiome

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Background: The impact of the gut microbiota on host physiology and behavior has been relatively well established. Whether changes in microbial composition affect brain structure and function is largely elusive, however. This is important as altered brain structure and function have been implicated in various neurodevelopmental disorders, like attention-deficit/hyperactivity disorder (ADHD). We hypothesized that gut microbiota of persons with and without ADHD, when transplanted into mice, would differentially modify brain function and/or structure. We investigated this by colonizing young, male, germ-free C57BL/6JOlaHsd mice with microbiota from individuals with and without ADHD. We generated and analyzed microbiome data, assessed brain structure and function by magnetic resonance imaging (MRI), and studied mouse behavior in a behavioral test battery.Results: Principal coordinate analysis showed a clear separation of fecal microbiota of mice colonized with ADHD and control microbiota. With diffusion tensor imaging, we observed a decreased structural integrity of both white and gray matter regions (i.e., internal capsule, hippocampus) in mice that were colonized with ADHD microbiota. We also found significant correlations between white matter integrity and the differentially expressed microbiota. Mice colonized with ADHD microbiota additionally showed decreased resting-state functional MRI-based connectivity between right motor and right visual cortices. These regions, as well as the hippocampus and internal capsule, have previously been reported to be altered in several neurodevelopmental disorders. Furthermore, we also show that mice colonized with ADHD microbiota were more anxious in the open-field test. Conclusions: Taken together, we demonstrate that altered microbial composition could be a driver of altered brain structure and function and concomitant changes in the animals' behavior. These findings may help to understand the mechanisms through which the gut microbiota contributes to the pathobiology of neurodevelopmental disorders.

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“…There is growing evidence associating the gut microbiota in the pathophysiology of depression. Several taxonomic association studies in humans have observed differences in the fecal microbiota composition of MDD patients compared to healthy subjects [7–10]. These studies identified variation in the phyla Bacteroidetes, Proteobacteria, Actinobacteria and Firmicutes , and in the genera Enterobacteriaceae, Alistipes, Faecalibacterium, Bifidobacterium and Blautia , although contradicting results were found regarding the direction of the associations detected between disease and bacterial taxa.…”

Section: The Gut Microbiome Contributes To Depressive Behaviormentioning

confidence: 98%

Gut microbial metabolites in depression: understanding the biochemical mechanisms

et al. 2019

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Gastrointestinal and central function are intrinsically connected by the gut microbiota, an ecosystem that has co-evolved with the host to expand its biotransformational capabilities and interact with host physiological processes by means of its metabolic products. Abnormalities in this microbiota-gut-brain axis have emerged as a key component in the pathophysiology of depression, leading to more research attempting to understand the neuroactive potential of the products of gut microbial metabolism. This review explores the potential for the gut microbiota to contribute to depression and focuses on the role that microbially-derived molecules – neurotransmitters, short-chain fatty acids, indoles, bile acids, choline metabolites, lactate and vitamins – play in the context of emotional behavior. The future of gut-brain axis research lies is moving away from association, towards the mechanisms underlying the relationship between the gut bacteria and depressive behavior. We propose that direct and indirect mechanisms exist through which gut microbial metabolites affect depressive behavior: these include (i) direct stimulation of central receptors, (ii) peripheral stimulation of neural, endocrine, and immune mediators, and (iii) epigenetic regulation of histone acetylation and DNA methylation. Elucidating these mechanisms is essential to expand our understanding of the etiology of depression, and to develop new strategies to harness the beneficial psychotropic effects of these molecules. Overall, the review highlights the potential for dietary interventions to represent such novel therapeutic strategies for major depressive disorder.

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Exploration of microbiota targets for major depressive disorder and mood related traits

Cited by 119 publications

References 45 publications

Developmental exposure of California mice to endocrine disrupting chemicals and potential effects on the microbiome-gut-brain axis at adulthood

Developmental exposure of California mice to endocrine disrupting chemicals and potential effects on the microbiome-gut-brain axis at adulthood

Gut microbiota from persons with attention-deficit/hyperactivity disorder affects the brain in mice

Gut microbial metabolites in depression: understanding the biochemical mechanisms

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