Gastroenterology issues in schizophrenia: Why the gut matters

Severance, Emily G.

doi:10.1016/j.eurpsy.2016.01.841

Cited by 9 publications

(13 citation statements)

References 86 publications

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“…These overlapped pathways imply that, apart from dysbiotic gut microbiota, dysfunctional immune system may also underpin elevated SCFA production and/or absorption. Previous studies propose that increased SCFA in the systemic circulation may be facilitated by increased intestinal permeability [39, 55, 56], which are apparent in some patients with schizophrenia [57, 58]. Our human data reveal that sCD14, serological surrogate markers for both bacterial translocation and innate immune activation, are upregulated in schizophrenia and positively correlated with circulating SCFAs.…”

Section: Discussionsupporting

confidence: 53%

Role of short-chain fatty acids in the gut-brain axis in schizophrenia: contribution to immune activation and pathophysiology in humans and mice

Zhu

Wang

et al. 2020

Preprint

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Objective: Gut microbiota dysbiosis and aberrant gut-brain functional modules including short-chain fatty acid (SCFA) production and long-lasting immune activation (IA) are presented in schizophrenia. Given the key roles of gut microbiota and SCFA in shaping immunity, we propose that dysbiosis-induced SCFA upregulation could contribute to IA and behavioral symptoms in schizophrenia. Design: Gut microbiota, SCFA, and IA biomarkers were compared between schizophrenic patients and healthy controls. The roles of SCFA in schizophrenia-related IA were analyzed in cultured peripheral blood mononuclear cells (PBMCs) and a mouse model of schizophrenia. The effects of SCFAs on schizophrenia-related phenotypes were analyzed in both human and mouse. Results: Both microbial-derived SCFA and SCFA-producing bacteria were elevated in the guts of schizophrenic patients, and this increased SCFA production in gut was associated with IA in schizophrenia. The microbiome signature underpinning schizophrenia-related IA includes increased diversity and increased SCFA-producing bacteria and inflammation-associated bacteria. The impact of SCFAs on immune responses of cultured PBMC depend on the diagnosis and IA status of donors. Small-molecule serum filtrates from immune-activated schizophrenic patients increased the inflammatory response of PBMCs from healthy volunteers, which can be enhanced and attenuated by SCFAs supplementation and inhibition of SCFA signaling, respectively. Chronically elevated SCFAs in adolescence induced neuroinflammation and schizophrenia-like behaviors in adult mice. Moreover, Gut microbiota chronically elevated SCFAs in adult mice prenatally exposed to IA potentiated their expression of schizophrenia-like behaviors.Conclusion: microbiota-derived SCFAs are important mediators of dysregulated gut-brain axis and participant in pathogenesis via enhance IA in schizophrenia. Summary Significance of this study What is already known about this subject?Schizophrenia pathogenesis goes beyond the brain since increasing peripheral abnormalities are revealed including gut microbiota dysbiosis, GI dysfunction, and systemic immune activation (IA).Systemic IA/inflammation contributes to the neuroinflammation and brain impairment underlying schizophrenia, and adjunctive immunotherapy can improve psychotic symptoms. Short-chain fatty acids (SCFA) mediate the microbiota-gut-brain communication and modulate several pathways involved in schizophrenia, including pathways of immunity and neurotransmitters. What are the new findings?

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Section: Discussionsupporting

confidence: 53%

Role of short-chain fatty acids in the gut-brain axis in schizophrenia: contribution to immune activation and pathophysiology in humans and mice

Zhu

Wang

et al. 2020

Preprint

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“…Furthermore, gastrointestinal inflammation due to a dysfunctional immune response to pathogen infection and food antigens is also prevalent in schizophrenia 44,45 . These intestinal pathological conditions may disrupt the mucosal barrier and decrease immune surveillance towards foreign microbes 7 , increasing the possibility of observing oral bacteria in the gut.…”

Section: Discussionmentioning

confidence: 99%

“…Increasing evidence indicates that schizophrenia may be a systemic disorder with neuropsychiatric conditions in addition to psychosis 5 . Furthermore, the importance of inflammation 6 and the involvement of the gastrointestinal system 7 in schizophrenia have received attention.…”

Section: Introductionmentioning

confidence: 99%

Identification of gut microbiome markers for schizophrenia delineates a potential role of Streptococcus

Zhu

Wang

et al. 2019

Preprint

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46Emerging evidence has linked the gut microbiota to schizophrenia. However, the 47 functional changes in the gut microbiota and the biological role of individual bacterial 48 species in schizophrenia have not been explored systematically. Here, we 49 characterized the gut microbiota in schizophrenia using shotgun metagenomic 50 sequencing of feces from a discovery cohort of 90 drug-free patients and 81 controls, 51 as well as a validation cohort of 45 patients taking antipsychotics and 45 controls. We 52 screened 83 schizophrenia-associated bacterial species and constructed a classifier 53 comprising 26 microbial biomarkers that distinguished patients from controls with a 54 0.896 area under the receiver operating characteristics curve (AUC) in the discovery 55 cohort and 0.765 AUC in the validation cohort. Our analysis of fecal metagenomes 56 revealed that schizophrenia-associated gut-brain modules included short-chain fatty 57 acids synthesis, tryptophan metabolism, and synthesis/degradation of 58 neurotransmitters including glutamate, γ-aminobutyric acid, and nitric oxide. The 59 schizophrenia-enriched gut bacterial species include several oral cavity-resident 60 microbes, such as Streptococcus vestibularis. We transplanted Streptococcus 61 vestibularis into the gut of the mice with antibiotic-induced microbiota depletion to 62 explore its functional role. We observed that this microbe transiently inhabited the 63 mouse gut and this was followed by hyperactivity and deficit in social behaviors, 64 accompanied with altered neurotransmitter levels in peripheral tissues. In conclusion, 65 our study identified 26 schizophrenia-associated bacterial species representing 66 potential microbial targets for future treatment, as well as gut-brain modules, some of 67 which may give rise to new microbial metabolites involved in the development of 68 schizophrenia. 69 70 Schizophrenia is a severe psychiatric disorder associated with hallucinations, 71 delusions, and thought disorders perturbing perception and social interaction 1 . The 72 etiology of schizophrenia is not elucidated, but assumed to be multifactorial involving 73 genetic and environmental factors. Abnormalities of neurotransmitter systems have 74 been extensively studied especially focusing on aberration of signaling involving 75 dopamine, glutamate, and γ-aminobutyric acid (GABA) 2-4 . Increasing evidence 76 indicates that schizophrenia may be a systemic disorder with neuropsychiatric 77 conditions in addition to psychosis 5 . Furthermore, the importance of inflammation 6 78 and the involvement of the gastrointestinal system 7 in schizophrenia have received 79 attention. 80 The gut microbiota is reported to play an important role in neurogenerative 81 processes, and perturbation of the microbiota and microbial products have been 82 demonstrated to affect behavior 8-10 . Changes in the gut microbiota have been 83 associated with neurological 11 and neurodevelopmental disorders 12,13 , including 84 schizophrenia 14 . It was recently reported that fecal tr...

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“…Obecnie stawia się hipotezę, która łączy zaburzenia w składzie mikrobiomu jelitowego ze stanem zapalnym w obrębie układu pokarmowego [69]. Zatem spodziewana jest różnica w mikrobiomie jelitowym u pacjentów cierpiących z powodu zapalnych chorób jelit, a grupą kontrolną [65,70,71] U pacjentów z chorobami zapalnymi jelit obserwowany jest duży udział w składzie flory bakteryjnej bakterii z rodzaju Firmicutes oraz niedobór bakterii z rodzaju Bacteroidetes, aczkolwiek zauważalne jest duże zróżnicowanie w składzie flory jelitowej u osób chorych [65].…”

Section: Znaczenie Mikrobiomu Jelitowegounclassified

“…Currently, a hypothesis has been put forward that connects the abnormal changes in the intestinal microbiome with inflammation within the gastrointestinal tract [69]. Thus, there is expected a difference in the intestinal microbiome in patients suffering from inflammatory bowel diseases, and the control group [65,70,71].…”

Section: The Importance Of the Intestinal Microbiomementioning

confidence: 99%

Review paper. Gluten-related disorders and schizophrenia - potential linking mechanisms, diagnostic and therapeutic challenge

Tomaka

Karakuła-Juchnowicz

Morylowska-Topolska

et al. 2017

Current Problems of Psychiatry

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More and more evidence confirms the theory that the intake of cereal products containing gluten may play an important role in the pathogenesis of many diseases. There are also premises indicating the relationship between the so-called gluten-related diseases and the development and course of mental disorders, including schizophrenia.The aim of this article is to review the literature on the potential relationship between the consumption of gluten and schizophrenia, considering the etiopathogenesis and the role of gluten-free diet in the treatment of schizophrenia.Methods: There were analysed available research papers in PubMed and Google Scholar with the key words: schizophrenia, gluten-related disorders, allergy to grain products, celiac disease, microbiota, immune system, exorphins and time span: 1960-2016 .Conclusions: Existing research results indicate a possible relationship between diet rich in grain products with high gluten content and the occurrence or exacerbation of schizophrenia symptoms. However, further studies are necessary to: 1) identify groups of patients for whom the consumption of cereal products (gluten) is associated with a particular risk of schizophrenia exacerbation, 2) determine the mechanisms relating the consumption of gluten with the mental state of schizophrenic patients, 3) get the possible benefits of implementing gluten-free diet in patients with schizophrenia.Keywords: schizophrenia, gluten, celiac disease, gluten-related disorders, allergy to gluten. StreszczeniePrzybywa dowodów na to, iż w patogenezie wielu chorób istotną rolę może odgrywać spożywanie produktów zbożowych zawierających gluten. Istnieją także przesłanki wskazujące na związek tzw. chorób glutenozależnych z powstawaniem i przebiegiem zaburzeń psychicznych, w tym schizofrenii.Celem niniejszego artykułu jest przegląd literatury na temat potencjalnego związku pomiędzy spożyciem glutenu a schizofrenią, z uwzględnieniem etiopatogenezy oraz roli diety bezglutenowej w terapii schizofrenii.Metoda: Analizie poddano dostępne artykuły z bazy PubMed oraz Google Scholar przy użyciu słów-kluczy: schizofrenia, nadwrażliwość na gluten, alergia na produkty zbożowe, celiakia, mikrobiota, układ immunologiczny, egzorfiny oraz deskryptorów czasowych: 1960-2016 rok.Wnioski: Dotychczasowe wyniki badań wskazują na możliwy związek diety bogatej w produkty zbożowe z dużą zawartością glutenu na występowanie lub zaostrzanie objawów schizofrenii. Konieczne są jednak dalsze badania celem: 1) identyfikacji grup pacjentów, dla których spożywanie produktów zbożowych (glutenu) wiąże się ze szczególnym ryzykiem pogorszenia przebiegu schizofrenii, 2) ustalenia mechanizmów łączących spożywanie glutenu ze stanem psychicznym pacjentów ze schizofrenią, 3) możliwych korzyści z wdrożenia diety bezglutenowej u pacjentów ze schizofrenią.

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Gastroenterology issues in schizophrenia: Why the gut matters

Cited by 9 publications

References 86 publications

Role of short-chain fatty acids in the gut-brain axis in schizophrenia: contribution to immune activation and pathophysiology in humans and mice

Role of short-chain fatty acids in the gut-brain axis in schizophrenia: contribution to immune activation and pathophysiology in humans and mice

Identification of gut microbiome markers for schizophrenia delineates a potential role of Streptococcus

Review paper. Gluten-related disorders and schizophrenia - potential linking mechanisms, diagnostic and therapeutic challenge

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