Mitochondria could be a potential key mediator linking the intestinal microbiota to depression

Chen, Jiezhong; Vitetta, Luis

doi:10.1002/jcb.29311

Cited by 27 publications

(22 citation statements)

References 91 publications

(292 reference statements)

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“…Gut microbiota has often been linked with metabolic diseases such as NAFLD, diabetes and obesity [ 3 , 4 ]. Many studies have shown that dysregulation of the intestinal microbiota (gut dysbiosis) can lead to NAFLD [ 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications

Chen¹,

Vitetta

2020

IJMS

Self Cite

194

137

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Gut microbiota dysregulation plays a key role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) through its metabolites. Therefore, the restoration of the gut microbiota and supplementation with commensal bacterial metabolites can be of therapeutic benefit against the disease. In this review, we summarize the roles of various bacterial metabolites in the pathogenesis of NAFLD and their therapeutic implications. The gut microbiota dysregulation is a feature of NAFLD, and the signatures of gut microbiota are associated with the severity of the disease through altered bacterial metabolites. Disturbance of bile acid metabolism leads to underactivation of bile acid receptors FXR and TGR5, causal for decreased energy expenditure, increased lipogenesis, increased bile acid synthesis and increased macrophage activity. Decreased production of butyrate results in increased intestinal inflammation, increased gut permeability, endotoxemia and systemic inflammation. Dysregulation of amino acids and choline also contributes to lipid accumulation and to a chronic inflammatory status. In some NAFLD patients, overproduction of ethanol produced by bacteria is responsible for hepatic inflammation. Many approaches including probiotics, prebiotics, synbiotics, faecal microbiome transplantation and a fasting-mimicking diet have been applied to restore the gut microbiota for the improvement of NAFLD.

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Section: Introductionmentioning

confidence: 99%

Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications

Chen¹,

Vitetta

2020

IJMS

Self Cite

194

137

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“…The probiotic Faecalibacterium prausnitzii is known to confer an antidepressive effect through its ability to produce an abundance of butyrate and reduce IL-6 level [38]. Butyrate, a short-chain fatty acid (SCFA) produced by gut microbiota, confers a protective role on the gut permeability and exerts anti-inflammatory effects on various organs including the brain [114]. Butyrate has been demonstrated to ameliorate depressive symptoms and likened to an anti-depressant in mice models [58].…”

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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“…The development of autism spectrum disorder possibly implicates mediating effects of mitochondrial function induced by colonic butyrate [14]. Neuronal mitochondrial dysfunction (affecting neuronal function and neuron cell numbers) may mediate the effects of gut dysbiosis on depression [51]. Possible pathways include SCFAs, brain inflammatory processes following gut permeability and increased blood lipopolysaccharide (LPS) levels [51].…”

Section: Mitochondrial Functionmentioning

confidence: 99%

Dietary Influences on the Microbiota–Gut–Brain Axis

Barber

Valsamakis

Mastorakos

et al. 2021

IJMS

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Over unimaginable expanses of evolutionary time, our gut microbiota have co-evolved with us, creating a symbiotic relationship in which each is utterly dependent upon the other. Far from confined to the recesses of the alimentary tract, our gut microbiota engage in complex and bi-directional communication with their host, which have far-reaching implications for overall health, wellbeing and normal physiological functioning. Amongst such communication streams, the microbiota–gut–brain axis predominates. Numerous complex mechanisms involve direct effects of the microbiota, or indirect effects through the release and absorption of the metabolic by-products of the gut microbiota. Proposed mechanisms implicate mitochondrial function, the hypothalamus–pituitary–adrenal axis, and autonomic, neuro-humeral, entero-endocrine and immunomodulatory pathways. Furthermore, dietary composition influences the relative abundance of gut microbiota species. Recent human-based data reveal that dietary effects on the gut microbiota can occur rapidly, and that our gut microbiota reflect our diet at any given time, although much inter-individual variation pertains. Although most studies on the effects of dietary macronutrients on the gut microbiota report on associations with relative changes in the abundance of particular species of bacteria, in broad terms, our modern-day animal-based Westernized diets are relatively high in fats and proteins and impoverished in fibres. This creates a perfect storm within the gut in which dysbiosis promotes localized inflammation, enhanced gut wall permeability, increased production of lipopolysaccharides, chronic endotoxemia and a resultant low-grade systemic inflammatory milieu, a harbinger of metabolic dysfunction and many modern-day chronic illnesses. Research should further focus on the colony effects of the gut microbiota on health and wellbeing, and dysbiotic effects on pathogenic pathways. Finally, we should revise our view of the gut microbiota from that of a seething mass of microbes to one of organ-status, on which our health and wellbeing utterly depends. Future guidelines on lifestyle strategies for wellbeing should integrate advice on the optimal establishment and maintenance of a healthy gut microbiota through dietary and other means. Although we are what we eat, perhaps more importantly, we are what our gut microbiota thrive on and they thrive on what we eat.

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Mitochondria could be a potential key mediator linking the intestinal microbiota to depression

Cited by 27 publications

References 91 publications

Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications

Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications

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

Dietary Influences on the Microbiota–Gut–Brain Axis

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