Microbiome Profiling Reveals Gut Dysbiosis in the Metabotropic Glutamate Receptor 5 Knockout Mouse Model of Schizophrenia

Gubert, Carolina; Kong, Geraldine; Uzungil, Volkan; Zeleznikow-Johnston, Ariel M; Burrows, Emma L.; Renoir, Thibault; Hannan, Anthony J

doi:10.3389/fcell.2020.582320

Cited by 18 publications

(18 citation statements)

References 92 publications

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“…A decrease in diversity of family Erysipelotrichaceae and genus Allobaculum , along with a dysbiosis, has been reported in the metabotropic glutamate receptor 5 (mGlu5) knockout mice model of SCZ ( Gubert et al, 2020 ). Further, a significantly low level of Bifidobacterium, Lactobacillus, E. coli , and a higher level of Clostridium coccoides were reported in fecal samples of SCZ individuals compared to healthy subjects ( Cuomo et al, 2018 ).…”

Section: Altered Gut Microbiota Inflammation and Neurodevelopmental D...mentioning

confidence: 99%

Understanding the Role of the Gut Microbiome in Brain Development and Its Association With Neurodevelopmental Psychiatric Disorders

Dash

Syed

Khan

2022

Front. Cell Dev. Biol.

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The gut microbiome has a tremendous influence on human physiology, including the nervous system. During fetal development, the initial colonization of the microbiome coincides with the development of the nervous system in a timely, coordinated manner. Emerging studies suggest an active involvement of the microbiome and its metabolic by-products in regulating early brain development. However, any disruption during this early developmental process can negatively impact brain functionality, leading to a range of neurodevelopment and neuropsychiatric disorders (NPD). In this review, we summarize recent evidence as to how the gut microbiome can influence the process of early human brain development and its association with major neurodevelopmental psychiatric disorders such as autism spectrum disorders, attention-deficit hyperactivity disorder, and schizophrenia. Further, we discuss how gut microbiome alterations can also play a role in inducing drug resistance in the affected individuals. We propose a model that establishes a direct link of microbiome dysbiosis with the exacerbated inflammatory state, leading to functional brain deficits associated with NPD. Based on the existing research, we discuss a framework whereby early diet intervention can boost mental wellness in the affected subjects and call for further research for a better understanding of mechanisms that govern the gut-brain axis may lead to novel approaches to the study of the pathophysiology and treatment of neuropsychiatric disorders.

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Section: Altered Gut Microbiota Inflammation and Neurodevelopmental D...mentioning

confidence: 99%

Understanding the Role of the Gut Microbiome in Brain Development and Its Association With Neurodevelopmental Psychiatric Disorders

Dash

Syed

Khan

2022

Front. Cell Dev. Biol.

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“…Furthermore, we did not measure parameters as feeding behavior, thermogenic parameters, sex specific differences, as well as the predominant cell population responsible for producing the cytokines modulated by the absence of mGluR5 in the adipose tissue. Finally, some evidence show that mGluR5 ablation may affect gut microbiota composition, aging, neurodegeneration, sex-dependent behavior and cognitive functions 55 – 57 . Thus, given the importance of those factors in the metabolism and obesity, as well as in the progress of a neurodegenerative environment, a deeper investigation of the central mechanisms of energy balance, and cognitive function in our model is needed in order to elucidate how peripheral metabolic and immunomodulatory events promoted by absence of mGluR5, may modulate these central highpoints.…”

Section: Discussionmentioning

confidence: 99%

Metabotropic glutamate receptor 5 knockout rescues obesity phenotype in a mouse model of Huntington’s disease

Santos

Ribeiro

Ferreira-Vieira

et al. 2022

Sci Rep

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Obesity represents a global health problem and is characterized by metabolic dysfunctions and a low-grade chronic inflammatory state, which can increase the risk of comorbidities, such as atherosclerosis, diabetes and insulin resistance. Here we tested the hypothesis that the genetic deletion of metabotropic glutamate receptor 5 (mGluR5) may rescue metabolic and inflammatory features present in BACHD mice, a mouse model of Huntington’s disease (HD) with an obese phenotype. For that, we crossed BACHD and mGluR5 knockout mice (mGluR5−/−) in order to obtain the following groups: Wild type (WT), mGluR5−/−, BACHD and BACHD/mGluR5−/− (double mutant mice). Our results showed that the double mutant mice present decreased body weight as compared to BACHD mice in all tested ages and reduced visceral adiposity as compared to BACHD at 6 months of age. Additionally, 12-month-old double mutant mice present increased adipose tissue levels of adiponectin, decreased leptin levels, and increased IL-10/TNF ratio as compared to BACHD mice. Taken together, our preliminary data propose that the absence of mGluR5 reduce weight gain and visceral adiposity in BACHD mice, along with a decrease in the inflammatory state in the visceral adipose tissue (VAT), which may indicate that mGluR5 may play a role in adiposity modulation.

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“…Metabotropic glutamate receptors (mGluRs) exert fine control over glutamate activity. Gut dysbiosis in KO mice indicates a link between glutamate regulation and gut microbiota that was disturbed in the mGlu5 KO mouse, thus resulting in gut dysbiosis [ 21 ].…”

Section: A Tridimensional Relationship Of Gut Microbial Diversity Neu...mentioning

confidence: 99%

Modulation of Gut Microbial Diversity through Non-Pharmaceutical Approaches to Treat Schizophrenia

Munawar

Ahmad

Anwar

et al. 2022

IJMS

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Schizophrenia (SCZ) is a psychotic syndrome with well-defined signs and symptoms but indecisive causes and effective treatment. Unknown underpinning reasons and no cure of the disease profoundly elevate the risk of illness. Gut microbial dysbiosis related metabolic dysfunction is providing a new angle to look at the potential causes and treatment options for schizophrenia. Because of the number of side effects, including gut dysbiosis, of traditional antipsychotic drugs, new alternative therapeutic options are under consideration. We propose that non-pharmacotherapy using biotherapeutic products could be a potent treatment to improve cognitive impairment and other symptoms of schizophrenia. Use of live microorganisms (probiotics), fibers (prebiotics), and polyphenols alone or in a mixture can maintain gut microbial diversity and improve the two-way relationship of the gut microbiota and the central nervous system. Fiber and polyphenol induced management of gut microbiota may positively influence the gut–brain axis by increasing the level of brain-derived neurotrophic factors involved in schizophrenia. Furthermore, we endorse the need for comprehensive clinical assessment and follow-up of psychobiotic (pro and prebiotics) treatment in mental illness to estimate the level of target recovery and disability reduction in schizophrenia.

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Microbiome Profiling Reveals Gut Dysbiosis in the Metabotropic Glutamate Receptor 5 Knockout Mouse Model of Schizophrenia

Cited by 18 publications

References 92 publications

Understanding the Role of the Gut Microbiome in Brain Development and Its Association With Neurodevelopmental Psychiatric Disorders

Understanding the Role of the Gut Microbiome in Brain Development and Its Association With Neurodevelopmental Psychiatric Disorders

Metabotropic glutamate receptor 5 knockout rescues obesity phenotype in a mouse model of Huntington’s disease

Modulation of Gut Microbial Diversity through Non-Pharmaceutical Approaches to Treat Schizophrenia

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