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Journal ArticleDOI: 10.1016/J.PNPBP.2020.110097

Gut microbiota: An intermediary between metabolic syndrome and cognitive deficits in schizophrenia.

02 Mar 2021-Progress in Neuro-psychopharmacology & Biological Psychiatry (Elsevier)-Vol. 106, pp 110097
Abstract: Gut microbiome interacts with the central nervous system tract through the gut-brain axis. Such communication involves neuronal, endocrine, and immunological mechanisms, which allows for the microbiota to affect and respond to various behaviors and psychiatric conditions. In addition, the use of atypical antipsychotic drugs (AAPDs) may interact with and even change the abundance of microbiome to potentially cause adverse effects or aggravate the disorders inherent in the disease. The regulate effects of gut microbiome has been described in several psychiatric disorders including anxiety and depression, but only a few reports have discussed the role of microbiota in AAPDs-induced Metabolic syndrome (MetS) and cognitive disorders. The following review systematically summarizes current knowledge about the gut microbiota in behavior and psychiatric illness, with the emphasis of an important role of the microbiome in the metabolism of schizophrenia and the potential for AAPDs to change the gut microbiota to promote adverse events. Prebiotics and probiotics are microbiota-management tools with documented efficacy for metabolic disturbances and cognitive deficits. Novel therapies for targeting microbiota for alleviating AAPDs-induced adverse effects are also under fast development.

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Topics: Microbiome (59%), Gut flora (57%)
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Open access
Stig Bengmark1Institutions (1)
15 Oct 2012-
Abstract: The microbiota of Westerners is significantly reduced in comparison to rural individuals living a similar lifestyle to our Paleolithic forefathers but also to that of other free-living primates such as the chimpanzee The great majority of ingredients in the industrially produced foods consumed in the West are absorbed in the upper part of small intestine and thus of limited benefit to the microbiota Lack of proper nutrition for microbiota is a major factor under-pinning dysfunctional microbiota, dysbiosis, chronically elevated inflammation, and the production and leakage of endotoxins through the various tissue barriers Furthermore, the over-comsumption of insulinogenic foods and proteotoxins, such as advanced glycation and lipoxidation molecules, gluten and zein, and a reduced intake of fruit and vegetables, are key factors behind the commonly observed elevated inflammation and the endemic of obesity and chronic diseases, factors which are also likely to be detrimental to microbiota As a consequence of this lifestyle and the associated eating habits, most barriers, including the gut, the airways, the skin, the oral cavity, the vagina, the placenta, the blood–brain barrier, etc, are increasingly permeable Attempts to recondition these barriers through the use of so called ‘probiotics’, normally applied to the gut, are rarely successful, and sometimes fail, as they are usually applied as adjunctive treatments, eg in parallel with heavy pharmaceutical treatment, not rarely consisting in antibiotics and chemotherapy It is increasingly observed that the majority of pharmaceutical drugs, even those believed to have minimal adverse effects, such as proton pump inhibitors and anti-hypertensives, in fact adversely affect immune development and functions and are most likely also deleterious to microbiota Equally, it appears that probiotic treatment is not compatible with pharmacological treatments Eco-biological treatments, with plant-derived substances, or phytochemicals, eg curcumin and resveratrol, and pre-, pro- and syn-biotics offers similar effects as use of biologicals, although milder but also free from adverse effects Such treatments should be tried as alternative therapies; mainly, to begin with, for disease prevention but also in early cases of chronic diseases Pharmaceutical treatment has, thus far, failed to inhibit the tsunami of endemic diseases spreading around the world, and no new tools are in sight Dramatic alterations, in direction of a paleolithic-like lifestyle and food habits, seem to be the only alternatives with the potential to control the present escalating crisis The present review focuses on human studies, especially those of clinical relevance

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Topics: Dysbiosis (59%), Gut flora (52%)

10 Citations


Open accessJournal ArticleDOI: 10.3389/FCELL.2020.582320
Abstract: Schizophrenia (SZ) is a psychiatric disorder that constitutes one of the top 10 global causes of disability. More recently, a potential pathogenic role for the gut microbial community (microbiota) has been highlighted, with numerous studies describing dysregulated microbial profiles in SZ patients when compared to healthy controls. However, no animal model of SZ has previously recapitulated the gut dysbiosis observed clinically. Since the metabotropic glutamate receptor 5 (mGlu5) knockout mice provide a preclinical model of SZ with strong face and predictive validity, in the present study we performed gut microbiome profiling of mGlu5 knockout (KO) and wild-type (WT) mice by 16S rRNA sequencing of bacterial genomic DNA from fecal samples, analyzing bacterial diversity and taxonomic composition, as well as gastrointestinal parameters as indicators of gut function. We found a significant genotype difference in microbial beta diversity. Analysis of composition of microbiomes (ANCOM) models were performed to evaluate microbiota compositions, which identified a decreased relative abundance of the Erysipelotrichaceae family and Allobaculum genus in this mouse model of SZ. We also identified a signature of bacteria discriminating between the genotypes (KO and WT), consisting of the Erysipelotrichales, Bacteroidales, and Clostridiales orders and macroscopic gut differences. We thus uncovered global differential community composition in the gut microbiota profile between mGlu5 KO and WT mice, outlining the first evidence for gut dysbiosis in a genetic animal model of SZ. Our findings suggest that this widely used preclinical model of SZ also has substantial utility for investigations of gut dysbiosis and associated signaling via the microbiota-gut-brain axis, as potential modulators of SZ pathogenesis. Our discovery opens up new avenues to explore gut dysbiosis and its proposed links to brain dysfunction in SZ, as well as novel therapeutic approaches to this devastating disorder.

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Topics: Microbiome (53%), Gut flora (53%)

8 Citations


Open accessJournal ArticleDOI: 10.1016/J.COPH.2021.09.003
Lumei Huang1, Beáta Sperlágh1Institutions (1)
Abstract: Schizophrenia is a common psychiatric disorder which affects approximately 1% of the population worldwide. However, the complexity of etiology, treatment resistance and side effects induced by current antipsychotics, relapse prevention, and psychosocial rehabilitation are still to be uncovered. Caffeine, as the world's most widely consumed psychoactive drug, plays a crucial role in daily life. Plenty of preclinical and clinical evidence has illustrated that caffeine consumption could have a beneficial effect on schizophrenia. In this review, we firstly summarize the factors associated with the caffeine-induced beneficial effect. Then, a variety of mechanism of actions independent of adenosine receptor signaling will be discussed with an emphasis on the potential contribution of the microbiome–gut–brain axis to provide more possibilities for future therapeutic, prognosis, and social rehabilitation strategy.

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Topics: Population (52%), Psychoactive drug (52%)

Open accessJournal ArticleDOI: 10.3389/FNSYS.2021.704069
Chong Wang, Teng Zhang, Lei He, Ji-Yong Fu  +3 moreInstitutions (2)
Abstract: Objective: Accumulating evidence indicates that inflammation abnormalities may contribute to aggression behaviors in psychotic patients, however, the possible sources of inflammation remain elusive. We aimed to evaluate the associations among aggression, inflammation, and bacterial translocation (BT) in aggression-affected schizophrenia (ScZ) inpatients with 2 weeks of antipsychotics discontinuation. Methods: Serum specimens collected from 112 aggression and 112 non-aggression individuals with ScZ and 56 healthy adults were used for quantifications of inflammation- or BT-related biomarkers. Aggression severity was assessed by Modified Overt Aggression Scale (MOAS). Results: Proinflammation phenotype dominated and leaky gut-induced BT occurred only in cases with ScZ with a history of aggression, and the MOAS score positively related to levels of C-reactive protein, interleukin (IL)-6, IL-1β, and tumor necrosis factor-α. Furthermore, serum levels of BT-derived lipopolysaccharide (LPS), as well as LPS-responded soluble CD14, were not only positively correlated with levels of above proinflammation mediators but also the total MOAS score and subscore for aggression against objects or others. Conclusion: Our results collectively demonstrate the presence of leaky gut and further correlate BT-derived LPS and soluble CD14 to onset or severity of aggression possibly by driving proinflammation response in inpatients with ScZ, which indicates that BT may be a novel anti-inflammation therapeutic target for aggression prophylaxis.

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Journal ArticleDOI: 10.2174/1381612827666210804110139
Abstract: BACKGROUND Diagnosis of schizophrenia lacks reliable medical diagnostic tests and robust biomarkers applied to clinical practice. Schizophrenic patients undergoing treatment with antipsychotics suffer reduced life expectancy due to metabolic disarrangements that co-exist with their mental illness and predispose them to develop metabolic syndrome, which is also exacerbated by medication. Metabolomics is an emerging and potent technology able to accelerate this biomedical research. AIM This review focus on a detailed vision of the molecular mechanisms involved both in schizophrenia and antipsychotic-induced metabolic syndrome, based on innovative metabolites that consistently change in nascent metabolic syndrome, drug-naive, first episode psychosis and/or schizophrenic patients compared to healthy subjects. Main Lines: Supported by metabolomic approaches, although not exclusively, noteworthy variations are reported mainly through serum samples of patients and controls in several scenes: 1) alterations in fatty acids, inflammatory response indicators, amino acids and biogenic amines, biometals, and gut microbiota metabolites (schizophrenia); 2) alterations in metabolites involved in carbohydrate and gut microbiota metabolism, inflammation and oxidative stress (metabolic syndrome), some of them shared with schizophrenia; 3) alterations of cytokines secreted by adipose tissue, phosphatidylcholines, acylcarnitines, Sirtuin 1, orexin-A, and changes in microbiota composition (antipsychotic-induced metabolic syndrome). CONCLUSION Novel insights into the pathogenesis of schizophrenia and metabolic side-effects associated with its antipsychotic treatment represent an urgent request for scientists and clinicians. Leptin, carnitines, adiponectin, insulin, or interleukin-6 represent some examples of candidate biomarkers. Cutting-edge technologies like metabolomics have the power to strengthen research for achieving preventive, diagnostic, and therapeutical solutions for schizophrenia.

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Topics: Metabolic syndrome (53%), Schizophrenia (52%)

References
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217 results found


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25 Oct 2005-Circulation
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9,226 Citations


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Gökhan S. Hotamisligil1Institutions (1)
14 Dec 2006-Nature
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Open accessJournal ArticleDOI: 10.1038/NATURE07540
22 Jan 2009-Nature
Abstract: The human distal gut harbours a vast ensemble of microbes (the microbiota) that provide important metabolic capabilities, including the ability to extract energy from otherwise indigestible dietary polysaccharides. Studies of a few unrelated, healthy adults have revealed substantial diversity in their gut communities, as measured by sequencing 16S rRNA genes, yet how this diversity relates to function and to the rest of the genes in the collective genomes of the microbiota (the gut microbiome) remains obscure. Studies of lean and obese mice suggest that the gut microbiota affects energy balance by influencing the efficiency of calorie harvest from the diet, and how this harvested energy is used and stored. Here we characterize the faecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers, to address how host genotype, environmental exposure and host adiposity influence the gut microbiome. Analysis of 154 individuals yielded 9,920 near full-length and 1,937,461 partial bacterial 16S rRNA sequences, plus 2.14 gigabases from their microbiomes. The results reveal that the human gut microbiome is shared among family members, but that each person's gut microbial community varies in the specific bacterial lineages present, with a comparable degree of co-variation between adult monozygotic and dizygotic twin pairs. However, there was a wide array of shared microbial genes among sampled individuals, comprising an extensive, identifiable 'core microbiome' at the gene, rather than at the organismal lineage, level. Obesity is associated with phylum-level changes in the microbiota, reduced bacterial diversity and altered representation of bacterial genes and metabolic pathways. These results demonstrate that a diversity of organismal assemblages can nonetheless yield a core microbiome at a functional level, and that deviations from this core are associated with different physiological states (obese compared with lean).

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Topics: Microbiome (64%), Human Microbiome Project (63%), Human microbiome (58%) ... read more

6,178 Citations


Open accessJournal ArticleDOI: 10.1111/J.1464-5491.2006.01858.X
01 May 2006-Diabetic Medicine
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5,065 Citations


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