ArticleLiterature Review

The “psychomicrobiotic”: Targeting microbiota in major psychiatric disorders: A systematic review

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Abstract

The gut microbiota is increasingly considered as a symbiotic partner in the maintenance of good health. Metagenomic approaches could help to discover how the complex gut microbial ecosystem participates in the control of the host's brain development and function, and could be relevant for future therapeutic developments, such as probiotics, prebiotics and nutritional approaches for psychiatric disorders. Previous reviews focused on the effects of microbiota on the central nervous system in in vitro and animal studies. The aim of the present review is to synthetize the current data on the association between microbiota dysbiosis and onset and/or maintenance of major psychiatric disorders, and to explore potential therapeutic opportunities targeting microbiota dysbiosis in psychiatric patients. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

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... However, food poisoning cases due to certain plant toxins are also reported from time to time. In general, the effects will depend on the amount of the plant ingested, the level of toxins present (which can widely vary according to the species, growth conditions and geographical factors, as well as to food processing procedures applied), their mechanism of action and potency, and the susceptibility of the individual, but very severe symptoms and even death may occur (Saravanan et al., 2016;Fletcher and Netzel, 2020). Some examples of toxins found in edible plants are shown in Table 2. Of these, lectins seem to be relevant for causing chronic dysbiosis (see Gut-Microbiota and Toxic Dietary Components section). ...
... The main bacterial toxins found in foods and their toxic effects are shown in Table 3. In addition to their contribution to foodborne disease, marine biotoxins (i.e., brevetoxins, ciguatoxin, domoic acid, okadaic acid, saxitoxin, tetrodotoxin), have become tools to reveal the function of numerous cellular proteins essential for life, such as ion channels and membrane receptors (Chekan et al., 2020;Fletcher and Netzel, 2020). The natural food contaminants most relevant regarding chronic disease and gut microbiota are probably mycotoxins. ...
... According to the evidence, environmental chemicals have toxic effects on gut-microbiota and in the brain through GBA. In this context, several studies have shown that the manipulation of the intestinal microbiota with probiotics and prebiotics, among others, causes changes in the gut microbiota, in the functioning of the GBA, as well as behavioral changes (Fond et al., 2015). This leads to the interesting idea that modulation of the gut microbiota could be an effective strategy to reduce toxic effects of environmental chemicals. ...
Chapter
Environmental pollutants are present everywhere, in every breath and every bite, as well as in the air, food or water. These environmental pollutants may be natural or anthropogenic, and therefore this article focuses on pesticides, heavy metals or toxic dietary components. We will discuss the relationship between these pollutants and the gut microbiota and how it affects certain diseases, for example, through the gut-brain axis. At last, intestinal modulation with prebiotics or probiotics will be introduced under these environmental pollutants conditions.
... Estima-se que 10 14 microrganismos residam no intestino de um adulto, quantia essa equivalente a dez vezes o número de células de todo o corpo humano [1][2][3] . A maior parte desses microrganismos são bactérias -denominadas "comensais" -, que, juntas, somam até 1.000 espécies distintas, e cujas quantidade e variedade pode variar devido a fatores como genética, idade, estresse, uso de fármacos e nutrição 1,4-6 . ...
... A maior parte desses microrganismos são bactérias -denominadas "comensais" -, que, juntas, somam até 1.000 espécies distintas, e cujas quantidade e variedade pode variar devido a fatores como genética, idade, estresse, uso de fármacos e nutrição 1,4-6 . Esses pequenos organismos contêm sua própria carga genética, de modo que o intestino humano apresenta mais de 3 milhões de genes microbiais -número que ultrapassa em muito a quantia de genes humanos (20.000) e que, por isso, têm sido chamados de "metagenoma" [1][2][3] . Projetos de larga escala como o Projeto Microbioma Humano (http:// commonfund.nih.gov/hmp) ...
... Atualmente, sabe-se que o eixo intestino-cérebro é constituído por rotas bidirecionais e, para comunicação, utiliza vias como o sistema nervoso parassimpático (em especial, o nervo vago), o sistema imune, o sistema neuroendócrino e o sistema circulatório -que permite a passagem de metabólitos e neurotransmissores produzidos pelo intestino 1,[8][9][10] . Recentemente, tornou-se evidente que a microbiota intestinal pode influenciar o funcionamento do eixo intestino--cérebro e alterar funções cerebrais e até mesmo o comportamento 2,5,11 . Essa descoberta se deu por diversos estudos realizados com: 1) animais (geralmente, camundongos) livres de germes [12][13][14][15] ; 2) animais tratados com probióticos, prebióticos ou antibióticos [16][17][18][19] ; e 3) transplante fecal [20][21][22] . ...
Article
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Objetivo: Reconhece-se atualmente a relevância do eixo intestino-cérebro para a compreensão de comportamentos e doenças mentais ou psiquiátricas. O presente estudo teve por objetivo analisar os efeitos do consumo de probióticos sobre sintomas depressivos e depressão maior. Métodos: O presente estudo constitui uma revisão de ensaios clínicos randomizados duplos-cegos ou triplos-cegos, placebo-controlados, publicados entre 2010 e 2020. Foi realizada busca por artigos nas bases de dados PubMed, ScienceDirect e Google Scholar. Resultados: Oito artigos compuseram a amostra do presente estudo. Os resultados entre estudos são controversos e indicam que a relação de causalidade entre o consumo de probióticos e o alívio de sintomas depressivos ainda não foi estabelecida. Conclusões: Mais ensaios clínicos randomizados duplos-cegos ou triplos-cegos, placebo-controlados, que controlem potenciais fatores de confusão (p. ex.: dieta, uso de antibióticos), são necessários para verificar consistentemente a relação causal entre o consumo de probióticos e o alívio de sintomas depressivos.
... Colonization of the newborn still begins in the womb, and bacteria have been detected in the umbilical cord, placenta, amniotic fluid, and meconium [13]. This is crucial for the development and functioning of the immune system, such that changes in the process will modify metabolic and immune responses in the host intestine, with the occurrence of chronic inflammation and oxidative stress [2,14,15]. ...
... The microbiota undergoes variations with the life cycle of the host, essentially during the period of intestinal colonization and childhood. Under certain circumstances, a relation of dysbiosis can be established [5,14] when a state in which the microbial composition and function change from its normal beneficial role to a deleterious role, with consequences for the health of the host [15]. ...
... Other studies have shown that pregnant women with a high-fat diet during gestation and breastfeeding had children with dysbiosis, which was maintained even after an isocaloric diet [10]. Dysbiosis promotes an increase in the synthesis of deleterious compounds (ammonia, phenols, indoles, amines, and sulfide) and a reduction of antioxidants [15]. Metabolites produced by commensal bacteria can affect the brain expression of important proteins in cognition, affecting host behavior [14]. ...
Article
Background There is increasing evidence of the influence of the intestinal microbiota on the disease processes of various organs and systems. Dysbiosis, that is, alteration of the composition and function of the microbiota may constitute an important risk factor for the development of mental disorders, namely, schizophrenia. Objective This works aims to review current evidence regarding the pathological mechanisms leading from dysbiosis to schizophrenia and in particular the deficit syndrome in schizophrenia. Methods Scientific articles from PubMed, SCOPUS, EMBASE and Web of Science Core Collection published between September 2017 and December 2020 were included in this review. Results The commensal intestinal flora plays an important role in neurodevelopment. In the presence of dysbiosis, this maturation is disturbed, resulting in the modification of brain structures and inflammatory responses at the intestinal, systemic and at the Central Nervous System (CNS) level. These disturbances may be linked to the development of symptoms of the disease. The microbiota exerts its influence on the CNS through several pathways, in this paper we focused on the membrane hypothesis and the inflammatory hypothesis. We explored the evidence concerning the use of probiotics, prebiotics, and fecal transplants. Conclusion Although there is no consensus regarding the alterations that could constitute a risk factor for schizophrenia, some of the species appear to be more frequently altered and their relationship with the host is dysregulated in patients at risk and with established schizophrenia, particularly in deficit schizophrenia.
... "Prebiotics" is a closely related approach, which involves nutritional modifications that nurture beneficial gut microflora. 44,45 Health-promoting species of gut microbiome contribute to health of the host by activating xenobiotic metabolism system, stimulating mucosal immunity (secretory IgA), inhibiting the growth of endotoxic bacteria, enhancing the expression of mucin, which promotes stability of the mucosal barrier, and synthesizing beneficial substances e.g., short-chain fatty acids, amino acids, antioxidants, and vitamin K. 24,29,44 Evolving knowledge denotes effectiveness of probiotics in the treatment of muscle wasting in cachectic animal models. Oral consumption of probiotics containing lactobacillus (L.) reuteri, L. gasseri, and L. plantarumby cachectic mice was associated with restoration of the normal structure and balance of bacterial phyla in the gut as well as with less intestinal permeability. ...
... "Prebiotics" is a closely related approach, which involves nutritional modifications that nurture beneficial gut microflora. 44,45 Health-promoting species of gut microbiome contribute to health of the host by activating xenobiotic metabolism system, stimulating mucosal immunity (secretory IgA), inhibiting the growth of endotoxic bacteria, enhancing the expression of mucin, which promotes stability of the mucosal barrier, and synthesizing beneficial substances e.g., short-chain fatty acids, amino acids, antioxidants, and vitamin K. 24,29,44 Evolving knowledge denotes effectiveness of probiotics in the treatment of muscle wasting in cachectic animal models. Oral consumption of probiotics containing lactobacillus (L.) reuteri, L. gasseri, and L. plantarumby cachectic mice was associated with restoration of the normal structure and balance of bacterial phyla in the gut as well as with less intestinal permeability. ...
... 24, 31 Evidence denotes that around 35% of lactic acid bacteria in fresh fruits and vegetables can successfully survive gastric conditions and reach the intestine. 24,44 Bee honey contains a variety of health-promoting lactic acid bacteria e.g., Bifidobacterium, Fructobacillus, and Lactobacillaceae. These bacterial species demonstrate strong antimicrobial activity even against the most antibiotic-resistant pathogens. ...
Article
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Current research emphasizes the contribution of gut microbiome to numerous health conditions including cancer and skeletomuscular disorders. Cachexia is a debilitating condition of progressive loss of body tissues. It occurs in up to 80% of patients with tumors, and it impairs their functioning and quality of life and increases morbidity and premature death. Several randomized trials indicate that interventions, which target gut microbiome can correct and revert tissue loss in aged people. However, less is known about the effect of such strategies in cachectic muscle loss. This report briefly sheds the light on the role of gut-muscle axis in cachexia and demonstrates few examples on interventions addressing gut microbiome and their effect on cachectic muscle. It also speculates the literature for the skeletal muscle-promoting activity of bee products, particularly bee honey and propolis (which are quite handy), within the context of cachexia. Implications for future studies are discussed.
... Prenatal exposure to LPS led to the development of ASD-like behavior [245]. Elevated levels of LPS were found in the blood of autistic subjects [246,247]. Animals with maternal immune activation (MIA) presented impaired GI barrier, elevated levels of IL-6, microbial dysbiosis in the intestines, and ASD-related behaviors (e.g., decreased ultrasonic vocalization as a mode of communication, altered olfactory communication, impaired social interactions and increased repetitive marble burying and self-grooming) when compared to the control group [248]. These changes were restored by colonization with Bacteroides fragilis. ...
... In the case of impaired BBB, which can be observed in certain (but not all) autistic subjects [37,254], LPS or SCFAs may cause brain inflammation and thus, further facilitate access to the brain for harmful substances, like heavy metals, that can accumulate there [228,246,255]. Both PET imaging and post-mortem studies revealed enhanced microglial activation in autistic people suggesting the presence of inflammation in the brain [226,256], whereas Erny and colleagues [257] demonstrated that proper functioning of the brain microglia needs the gut microbiome. ...
Article
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Emerging evidence indicates that the gut microbiota play a crucial role in the bidirectional communication between the gut and the brain suggesting that gut microbes may shape neural development, modulate neurotransmission and affect behavior, and thereby contribute to the pathogenesis and/or progression of many neurodevelopmental, neuropsychiatric, and neurological conditions. This review summarizes recent data on the role of microbiota–gut–brain axis in the pathophysiology of neuropsychiatric and neurological disorders including depression, anxiety, schizophrenia, autism spectrum disorders, Parkinson’s disease, migraine, and epilepsy. Also, the involvement of microbiota in gut disorders co-existing with neuropsychiatric conditions is highlighted. We discuss data from both in vivo preclinical experiments and clinical reports including: (1) studies in germ-free animals, (2) studies exploring the gut microbiota composition in animal models of diseases or in humans, (3) studies evaluating the effects of probiotics, prebiotics or antibiotics treatment as well as (4) the effects of fecal microbiota transplantation.
... Treatments for IBS and depressive symptoms are restricted by limited knowledge of underlying pathophysiology and lack of observable biomarkers (Canavan et al., 2014;Strawbridge et al., 2017). Emerging research suggests that dysbiosis of the gut microbiome may contribute to pathophysiology and offer a new target for treatment and symptom management for both IBS and depressive symptoms (Fond et al., 2015;Kennedy et al., 2014;Slyepchenko et al., 2017). Associations among IBS, depressive symptoms, and the gut microbiome each have been established independently, but the intersection of all three phenomenon has been less studied and therefore, is the focus of this review. ...
... This axis is the proposed mechanism that explains a connection between gut microbes, IBS, and depressive symptoms (Mayer et al., 2014;Rieder et al., 2017). The implication that the microbiome may be a new target for both treatment of IBS and depressive symptoms has prompted investigation of novel treatments including prebiotics, probiotics, and fecal transplants (Fond et al., 2015;Slyepchenko et al., 2017). ...
Article
Irritable bowel syndrome (IBS) is associated with depressive symptoms, but this relationship is poorly understood. Emerging research suggests that gut microbes are associated with symptoms in persons with IBS. The purpose of this integrative review is to describe the state of the science of the microbial relationship between IBS and depressive symptoms. PubMed, CINAHL, PsychINFO, and Web of Science were searched using “irritable bowel syndrome,” “microbiome,” “depression,” and related terms. Included articles were published in peer reviewed journals in English from 2009 to 2018. Studies on inflammatory bowel conditions, extra-intestinal microbiomes, or animal models were excluded. Fourteen quantitative studies met inclusion criteria, were critically appraised, and were analyzed using the Whittemore and Knafl method. Analysis revealed a consistently lower microbial biodiversity and lower proportions of Bifidobacterium and Lactobacillus in persons with IBS and co-occurring depressive symptoms. Inclusion of participants with moderate or greater depressive symptoms scores distinguished the studies which reported microbe differences in depressive symptoms. The results of this integrative review underscore the need for studies with larger samples and inclusion of a larger range of depressive symptoms guided by an overarching conceptual framework, such as the biopsychosocial ecology framework. This effort needs to be combined with longitudinal designs in order to identify related microbial markers.
... Under physiological conditions, they occur in specific quantities and proportions (Świerczyńska, 2020). Their abnormal composition or abnormal mutual relationship, called dysbiosis, prevents normal functioning of microbiota and contributes to the development of pathological processes (Fond et al., 2015). Dysbiosis affects the functioning of many organs and systems, including the central nervous system, through numerous interactions taking place along the pathway of the gut-brain axis (especially through increased permeability of the intestinal barrier) (Donaldson et al., 2016;Fond et al., 2015). ...
... Their abnormal composition or abnormal mutual relationship, called dysbiosis, prevents normal functioning of microbiota and contributes to the development of pathological processes (Fond et al., 2015). Dysbiosis affects the functioning of many organs and systems, including the central nervous system, through numerous interactions taking place along the pathway of the gut-brain axis (especially through increased permeability of the intestinal barrier) (Donaldson et al., 2016;Fond et al., 2015). Leaky intestinal epithelium enables the free flow of proinflammatory bacterial endotoxins, which affects the neuronal activity of the brain (in the limbic system) (Jiang et al., 2015;Marchesi et al., 2016). ...
Article
Although research into the aetiology and pathogenesis of eating disorders has been ongoing for many years, it has not yet been possible to identify all the factors responsible for their development. Current research does not focus on a single risk factor, but looks for correlations between them. This article presents selected aspects of the pathogenesis and risk factors of specific eating disorders. Family and individual factors, social and cultural factors, and biological factors are described. Particular attention has been paid to the aspect of parenting styles and behaviours exhibited, e.g. excessive punishment and emotional coldness. The coexistence of personality disorders with specific and non-specific eating disorders is also described. The social aspect highlights the development of social media and their impact on selfesteem, body dissatisfaction, and promotion of pathological thinness. Cultural factors include progressive “westernisation” and the rapid increase in the prevalence of eating disorders in the areas of the world where they did not previously exist. Among biological factors, publications on appetite neuromodulators, genetic factors, gut microbiota disorders, and the so-called brain-gut axis were analysed. Modern science is not as yet able to answer the question of which of the mentioned factors has the greatest impact on the development of eating disorders, however, ongoing research offers hope for effective treatment of these diseases in the future. Knowing the factors predisposing to their occurrence will allow early identification of risk groups and undertaking preventive and therapeutic actions, including psychotherapy and pharmacotherapy.
... They are products by live or attenuated microorganisms, such as bacteria or yeast, and they are commercially available diversifying from each other according to bacterial composition, and biological activity. The probiotics have many health benefits, such as competitive inhibition of non-commensal bacterial growth, improving immunity, and the production of many of the essential vitamins and cofactors needed for human health [131][132][133]. ...
... In any case, probiotics affect the homeostasis of the central nervous system [132][133][134]. It is very likely that the neurochemical and behavioral effects are mediated by the vagus nerve, as a communication pathway used by bacteria in the activation of communication between the intestine and the brain. ...
Article
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Adiponectin is an adipokine produced by adipose tissue. It has numerous beneficial effects. In particular, it improves metabolic effects and glucose homeostasis, lipid profile, and is involved in the regulation of cytokine profile and immune cell production, having anti-inflammatory and immune-regulatory effects. Adiponectin’s role is already known in immune diseases and also in neurodegenerative diseases. Neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, are a set of diseases of the central nervous system, characterized by a chronic and selective process of neuron cell death, which occurs mainly in relation to oxidative stress and neuroinflammation. Lifestyle is able to influence the development of these diseases. In particular, unhealthy nutrition on gut microbiota, influences its composition and predisposition to develop many diseases such as neurodegenerative diseases, given the importance of the “gut-brain” axis. There is a strong interplay between Adiponectin, gut microbiota, and brain-gut axis. For these reasons, a healthy diet composed of healthy nutrients such as probiotics, prebiotics, polyphenols, can prevent many metabolic and inflammatory diseases such as neurodegenerative diseases and obesity. The special Adiponectin role should be taken into account also, in order to be able to use this component as a therapeutic molecule.
... The GI microbiota, by its interaction with the host, plays an important role in maintaining health but it can also facilitate disease development (Hold and Hansen 2019). In animal models of gut dysbiosis, defined as a shift in microbial composition and function (Fond et al. 2015), it may affect such organs as the brain, lungs, and kidneys (Lukovic et al. 2019). Due to the high prevalence of GI cancers, relatively well-known effects of gut microbiota composition on GI tract functioning and easy access to fecal sampling, the most studies on the bacterial role in oncogenesis relate to the gut. ...
... Critchfield et al. (2011),Elson and Alexander (2015),Fond et al. (2015) and Karakula-Juchnowicz et al.(2016) Since the innate immune system can recognize such bacterial components as LPS, flagellin and peptidoglycan, gut microbiota dysbiosis can influence innate and adaptive immune responses involved in the tumor formation process Meng et al. (2018), Palm et al. (2015) and Vijay-Kumar and Gewirtz (2009) Bacterial metabolites Obesity in mice can result in the increased growth of Clostridia spp. producing deoxycholic acid, which can cause DNA damage and thus promote development of HCC Yoshimoto et al. (2013) and Raza et al. (2019) ...
Article
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Disturbances in gastrointestinal (GI) microbiota could play a significant role in the development of GI cancers, but the underlying mechanisms remain largely unclear. While some bacteria seem to facilitate carcinogenesis, others appear to be protective. So far only one bacterium ( Helicobacter pylori ) has been classified by the International Agency for Cancer Research as carcinogenic in humans but many other are the subject of intense research. Most studies on the role of microbiota in GI tract oncogenesis focus on pancreatic and colorectal cancers with the following three species: Helicobacter pylori, Escherichia coli , and Porphyromonas gingivalis as likely causative factors. This review summarizes the role of bacteria in GI tract oncogenesis.
... 78 It was demonstrated that the effect of the microbiome is not limited to general neurotransmission but is also involved in psychiatric, neurodevelopmental and neurodegenerative diseases. [79][80][81] The modulation of behavioural outcomes in psychiatric diseases is mediated by mechanisms such as neuropeptide synthesis, modulating neurotransmitter metabolizing enzymes and decreased absorption of biochemicals essential for the production of secondary metabolites required for communication via the gut-brain axis. 80 Furthermore, the gut microbiota has also been shown to play a role in postnatal brain development. ...
... [79][80][81] The modulation of behavioural outcomes in psychiatric diseases is mediated by mechanisms such as neuropeptide synthesis, modulating neurotransmitter metabolizing enzymes and decreased absorption of biochemicals essential for the production of secondary metabolites required for communication via the gut-brain axis. 80 Furthermore, the gut microbiota has also been shown to play a role in postnatal brain development. Several studies have reported a decrease in the synthesis of synaptogenic and synaptic scaffolding proteins like post-synaptic density (PSD -95), synaptophysin and Synapsin-1 in germ-free (GF) mice. ...
Article
The microbiome residing in the human gut performs a wide range of biological functions. Recently, it has been elucidated that a change in dietary habits is associated with alteration in the gut microflora which results in increased health risks and vulnerability towards various diseases. Falling in line with the same concept, depression has also been shown to increase its prevalence around the globe, especially in the western world. Various research studies have suggested that changes in the gut microbiome profile further result in decreased tolerance of stress. Although currently available medications help in relieving the symptoms of depressive disorders briefly, these drugs are not able to completely reverse the multifactorial pathology of depression. The discovery of the communication pathway between gut microbes and the brain, i.e. the Gut-Brain Axis, has led to new areas of research to find more effective and safer alternatives to current antidepressants. The use of probiotics and prebiotics has been suggested as being effective in various preclinical studies and clinical trials for depression. Therefore, in the present review, we address the new antidepressant mechanisms via gut microbe alterations and provide insight into how these can provide an alternative to antidepressant therapy without the side effects and risk of adverse drug reactions.
... Up to now, a limited, but significant number of studies, has provided evidence that mood disorders can be associated with marked changes of eCB signaling that can be mechanistically linked to depressive-like behaviors and alterations of microbiota environment. Although the relationship between gut dysbiosis and NPDs is increasingly documented (Fond et al., 2015;Cenit et al., 2017;Marrone and Coccurello, 2019), evidence for the involvement of eCB-microbiota axis in mood and neurodevelopmental disorders (NDDs) are much more limited. By contrast, recent studies have add evidence in support of the idea that alteration of the eCB signaling system can explain that is possible to use fecal microbiota transplantation (FMT) to transfer depression-like symptoms from "donors" to recipient mice (Chevalier et al., 2020). ...
Article
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The latest years have witnessed a growing interest towards the relationship between neuropsychiatric disease in children with autism spectrum disorders (ASD) and severe alterations in gut microbiota composition. In parallel, an increasing literature has focused the attention towards the association between derangement of the endocannabinoids machinery and some mechanisms and symptoms identified in ASD pathophysiology, such as alteration of neural development, immune system dysfunction, defective social interaction and stereotypic behavior. In this narrative review, we put together the vast ground of endocannabinoids and their partnership with gut microbiota, pursuing the hypothesis that the crosstalk between these two complex homeostatic systems (bioactive lipid mediators, receptors, biosynthetic and hydrolytic enzymes and the entire bacterial gut ecosystem, signaling molecules, metabolites and short chain fatty acids) may disclose new ideas and functional connections for the development of synergic treatments combining “gut-therapy,” nutritional intervention and pharmacological approaches. The two separate domains of the literature have been examined looking for all the plausible (and so far known) overlapping points, describing the mutual changes induced by acting either on the endocannabinoid system or on gut bacteria population and their relevance for the understanding of ASD pathophysiology. Both human pathology and symptoms relief in ASD subjects, as well as multiple ASD-like animal models, have been taken into consideration in order to provide evidence of the relevance of the endocannabinoids-microbiota crosstalk in this major neurodevelopmental disorder.
... The clinical studies for schizophrenia tend to be restricted and based on nutrition and probiotics, also utilizing antipsychotics (Fond et al., 2015). Dietary adjustments can influence both the intestinal microflora's composition and behaviour. ...
... Of consequence, some alterations in microbiota composition can change the function of these circuits. Interestingly the aforementioned process occurs simultaneously with the maturation of gut microbiota [42,43]. It has been shown that patients affected by BD present a developmental defect in the synaptic pruning process with consequent anomalies in the modulation of neuronal connectivity at the level of the ventral prefrontal cortex and the limbic cortex [44][45][46][47]. ...
Article
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The gut microbiota is the set of microorganisms that colonize the gastrointestinal tract of living creatures, establishing a bidirectional symbiotic relationship that is essential for maintaining homeostasis, for their growth and digestive processes. Growing evidence supports its involvement in the intercommunication system between the gut and the brain, so that it is called the gut–brain–microbiota axis. It is involved in the regulation of the functions of the Central Nervous System (CNS), behavior, mood and anxiety and, therefore, its implication in the pathogenesis of neuropsychiatric disorders. In this paper, we focused on the possible correlations between the gut microbiota and Bipolar Disorder (BD), in order to determine its role in the pathogenesis and in the clinical management of BD. Current literature supports a possible relationship between the compositional alterations of the intestinal microbiota and BD. Moreover, due to its impact on psychopharmacological treatment absorption, by acting on the composition of the microbiota beneficial effects can be obtained on BD symptoms. Finally, we discussed the potential of correcting gut microbiota alteration as a novel augmentation strategy in BD. Future studies are necessary to better clarify the relevance of gut microbiota alterations as state and disease biomarkers of BD.
... The LDA threshold is set to 2, and one against all (less strict) is selected for multi group comparison. stress on gut microbiota (Fond et al., 2015). Probiotics are not only related to the production of SCFAs (Pane et al., 2018) but have also been shown to reduce the mRNA expression of the GABA receptor and c-fos in the brain by regulating the gut-brain axis via the vagus nerve pathway regulate brain function and stress state Molina-Torres et al., 2019). ...
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Background Athletes will increase their state anxiety under stress situations, which will lead to the decline of sports performance. The improvement of anxiety by probiotics has been reported, but there is a lack of research in the athlete population. The purpose of the current study is to explore the effectiveness of probiotics in improving athletes’ state anxiety and sports performance under stress situations. Methods We conducted this single-arm study in Chongqing Institute of Sports Technology. In the 8-week study, 21 Chongqing young divers (mean age: 9.10 ± 1.80) were given probiotic Bifidobacterium animalis subsp. lactis BB-12 (1 × 10 ⁹ colony-forming units/100 g) daily. The state anxiety and sports performance of athletes were measured before, during, and after the intervention, and the gut microbiota of athletes was measured before and after the intervention. Results The intervention results showed that cognitive state anxiety, somatic state anxiety, and anxiety emotion were improved (cognitive: Z = −3.964, P < 0.001; somatic: Z = −3.079, P = 0.003; anxiety: Z = −2.973, P < 0.001). In terms of gut microbiota, the intervention did not change the gut microbial composition (such as α diversity and β diversity) but increased the abundance of Bifidobacteriaceae . At the 8th week, the performance of athletes under stress was significantly improved (χ ² = 7.88, P = 0.019). Limitations First of all, due to the restriction of the number of subjects in this study, there was no control group. Secondly, although the athletes’ diet was recorded in this study, the influence of this factor on gut microbiota was not eliminated. Finally, the anxiety level of the athletes in this study was obtained through a self-report, lacking physiological data in state anxiety. Conclusion The results show that probiotics intervention can improve the state anxiety of athletes under stress situation and improve the performance of athletes under stress situation.
... Likewise, assumption of tolerance and safety based on the non-pharmacological nature of these therapies should be questioned, since the risks of MTT are still unknown, and long-term effects of probiotics consumption remain unclear to date remain unclear to date. 12 Moreover, because microbiota is subject to dietary and pharmacological changes, novel research should take into consideration dietary status, and prebiotic/probiotic/antibiotic intake prior to enrollment in the study. ...
Article
Background and objectives The identification of findings that suggest a unique dysbiotic microbial signature in Autism Spectrum Disorders (ASD), has drawn the attention towards promising therapies for ASD targeting gut-microbiota. In order to help physicians to make clinical decisions based on significant evidence, this work offers a systematic review of original peer-reviewed studies focused on microbiota-targeted treatments in ASD children. Methods The systematic review was conducted following the PRISMA guidelines. Quality of research was assessed using the National Health and Medical Research Council (NHMRC). Of 110 potential records initially identified, only 9 articles accomplished our inclusion criteria. Results A decrease in specific Clostridiales species and/or an increase in Bacillales was consistent in several studies after the microbiota-targeted interventions, whereas mixed results were seen in other phyla, congruent with different baseline trends in their ASD samples. Behavioral and GI function responses varied across interventions. Conclusion Preliminary data show microbiota-based therapies to have a positive effect on ASD patients. However, further well-designed, large-scale randomized controlled trials with standardized protocols are needed to support the effectiveness and safety of these treatments.
... Since GM may influence host function beyond the gastrointestinal tract, GM is considered as a vital factor involved in the human physiological homeostasis and disease modulation [5][6][7]. Interestingly, there has been a growing evidence which shows a connection between GM and central nervous system: gut functions are affected by the emotional conditions such as stress, and GM may also affect the function of the brain [8][9][10][11][12]. Analysis of the cerebral metabolome demonstrated GM influenced cerebral metabolites such as dopamine and tryptophan, the precursor of serotonin [13]. ...
Article
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Gut microbiota (GM) plays a critical role in health maintenance. Previous reports connected GM with metabolic, immunologic and neurologic pathways. The main purpose of the current investigation was to study whether antibiotic-induced disturbances of GM affects psychological or behavioral conditions on mice as animal model. Mice were exposed to clindamycin or amoxicillin, and their behaviors were evaluated. Antibiotic-treated groups displayed reduced recognition memory and increased depression. No significant changes in the locomotor activity and anxiety were observed. Our data suggested that changes in GM composition by antibiotics may lead to the cognitive and behavioral deficit.
... Moreover, the gut microbiome, composed of bacteria, archaea, and eukaryotes colonized in the human gastrointestinal tract, with an approximate amount of human cells (Sender et al., 2016) is integrated to the GBA, constituting the so-called microbiota-gut-brain axis (MGBA). The gut microbiome has been found to be associated with the development of various diseases including obesity and types 2 diabetes (Allin et al., 2015;Tai et al., 2015), liver disease (Llorente and Schnabl, 2015), intestinal inflammatory syndromes (Goto et al., 2015;Wright et al., 2015), allergic diseases (McCoy and Koller, 2015), CNS diseases (Fond et al., 2015;Felice and O'Mahony, 2017;Bell et al., 2019), and autoimmune diseases (Johnson et al., 2015;Lerner and Matthias, 2015). ...
Article
Gastrointestinal signs and symptoms are the first signs of toxicity due to exposure to fluoride (F). This suggests the possibility that lower levels of subchronic F exposure may affect the gut. The aim of this study was to evaluate changes in the morphology, proteome and microbiome of the ileum of rats, after subchronic exposure to F. Male rats ingested water with 0, 10, or 50 mgF/L for thirty days. Treatment with F, regardless of the dose, significantly decreased the density of HuC/D-IR neurons, whereas CGRP-IR and SP-IR varicosities were significantly increased compared to the control group. Increased VIP-IR varicosities were significantly increased only in the group treated with 50 mgF/L. A significant increase in thickness of the tunica muscularis, as well as in the total thickness of the ileum wall was observed at both F doses when compared to controls. In proteomics analysis, myosin isoforms were increased, and Gastrotopin was decreased in F-exposed mice. In the microbiome metagenomics analysis, Class Clostridia was significantly reduced upon exposure to 10 mgF/L. At the higher F dose of 50 mg/L, Genus Ureaplasma was significantly reduced in comparison with controls. Morphological and proteomics alterations induced by F were marked by changes associated with inflammation, and alterations in the gut microbiome. Further studies are needed to determine whether F exposure increases inflammation with secondary effects of the gut microbiome, and/or whether primary effects of F on the gut microbiome enhance changes associated with inflammation.
... Regulating intestinal flora may be an effective method to prevent and treat psychiatric disorders. 55 ...
Article
Full-text available
Tea polyphenols (TP) are the most bioactive components in tea extracts. It has been reported that TP can regulate the composition and the function of the intestinal flora. Meanwhile, intestinal microorganisms improve the bioavailability of TP, and the corresponding metabolites of TP can regulate intestinal micro-ecology and promote human health more effectively. The dysfunction of the microbiota-gut-brain axis is the main pathological basis of depression, and its abnormality may be the direct cause and potential influencing factor of psychiatric disorders. The interrelationship between TP and intestinal microorganisms is discussed in this review, which will allow us to better evaluate the potential preventive effects of TP on psychiatric disorders by modulating host intestinal microorganisms.
... Since GM may influence host function beyond the gastrointestinal tract, GM is considered as a vital factor involved in the human physiological homeostasis and disease modulation [5][6][7]. Interestingly, there has been a growing evidence which shows a connection between GM and central nervous system: gut functions are affected by the emotional conditions such as stress, and GM may also affect the function of the brain [8][9][10][11][12]. Analysis of the cerebral metabolome demonstrated GM influenced cerebral metabolites such as dopamine and tryptophan, the precursor of serotonin [13]. ...
... Vegetables, especially leafy vegetables, are rich in dietary fibers, which are known to promote the growth of healthy bacteria in the gut [39]. In addition, the surface of fresh vegetables contains probiotic bacteria such as lactic acid bacteria-around 35% of these bacteria can survive gastric conditions and reach the gut to exert therapeutic effects [94]. Furthermore, research signifies the contribution of the complex carbohydrate content of low GI food to glycemic control via a complex mechanism that involves the regulation of gut microbiota [47,63]. ...
Article
Full-text available
Gestational diabetes mellitus (GDM) is a common pregnancy-related condition afflicting 5-36% of pregnancies. It is associated with many morbid maternal and fetal outcomes. Mood dysregulations (MDs, e.g., depression, distress, and anxiety) are common among women with GDM, and they exacerbate its prognosis and hinder its treatment. Hence, in addition to early detection and proper management of GDM, treating the associated MDs is crucial. Maternal hyperglycemia and MDs result from a complex network of genetic, behavioral, and environmental factors. This review briefly explores mechanisms that underlie GDM and prenatal MDs. It also describes the effect of exercise, dietary modification, and intermittent fasting (IF) on metabolic and affective dysfunctions exemplified by a case report. In this patient, interventions such as IF considerably reduced maternal body weight, plasma glucose, and psychological distress without any adverse effects. Thus, IF is one measure that can control GDM and maternal MDs; however, more investigations are warranted.
... In 2016, the intake of probiotics was observed to result in significant improvement in depressive symptoms [317]. A positive effect on the healthy population and depressed patients was observed only on the participants under 60 years, with no effects of probiotics on people aged above 65 years [318]. A variety of probiotics have been investigated in animal models of neurological disorders [319]. ...
... Taking into account modern knowledge about intestinal microbiota and its connection with the disorder of the nervous system development through the gut-brain axis [133][134][135], it can be concluded that during CVD, mediators from the intestine enter the brain with the bloodstream and lymph and activate hypothalamus nuclei. Then, as far as the hypothalamus is a suprasegmental integral center of the ANS, the sympathetic division of the ANS is activated [136,137]. ...
Article
Full-text available
Currently, a bidirectional relationship between the gut microbiota and the nervous system, which is considered as microbiota-gut-brain axis, is being actively studied. This axis is believed to be a key mechanism in the formation of somatovisceral functions in the human body. The gut microbiota determines the level of activation of the hypothalamic–pituitary system. In particular, the intestinal microbiota is an important source of neuroimmune mediators in the pathogenesis of cardiovascular disease. This review reflects the current state of publications in PubMed and Scopus databases until December 2020 on the mechanisms of formation and participation of neuroimmune mediators associated with gut microbiota in the development of cardiovascular disease.
... The clinical studies for schizophrenia tend to be restricted and based on nutrition and probiotics, also utilizing antipsychotics (Fond et al., 2015). Dietary adjustments can influence both the intestinal microflora's composition and behaviour. ...
... Sonuç olarak, bağırsak mikrobiyotası ve bakterilerin insan sağlığı üzerine etkileri önümüzdeki on yıl içinde nörobilimde ilgi odağı olacak gibi görünmektedir. Psikiyatrik bozuklukların tedavisinde mikroorganizmaları "psikomikrobiyotik" adıyla yeni bir ilaç grubu olarak sunan yazarlar da bulunmaktadır (Fond et al, 2015). Bağırsak beyin aksı belki de nöropsikiyatrik bozuklukların tam olarak anlaşılmasını ve tedavi edilmesini sağlayacak bir kayıp halkadır ve mutlaka daha fazla araştırma yapılması gerekmektedir. ...
... The pathophysiology of autism is not fully clear. However, children with ASD often have GI problems, such as indigestion, poor absorption, overgrowth of intestinal pathogenic bacteria and abnormal GI fistula [77]. Finegold et al. [78] reported that in patients with severe autism, Bacteroidetes and Actinobacteria phyla were at a higher level, while Firmicutes and Proteobacteria phyla were more abundant in the healthy individual. ...
Article
Full-text available
Recent advances in molecular genetics and the invention of new technologies led to a development in our knowledge about human microbiota, specifically bacterial one. The microbiota plays a fundamental role in the immunologic, hormonal and metabolic homeostasis of the host. After the initiation of the Human Microbiome Project, it became clear that the human microbiota consists of the 10-100 trillion symbiotic microbial cells harbored by each person, primarily bacteria in the gut, but also in other spots as the skin, mouth, nose, and vagina. Despite of the differences in studying bacterial species, decreased bacterial diversity and persistence has been connected with several diverse human diseases primarily diabetes, IBD (inflammatory bowel disease) and others; attempts were made even to explain psychiatric pathology. Several species emerged as dominant and were clearly linked to certain disorders or accepted as biomarkers of others. The current review aims to discuss key issues of our current knowledge about bacteria in human, the difficulties and methods of its analysis, its contribution to human health and responsibility for human diseases.
... Autism spectrum disorder (ASD) is a neurodevelopmental disorder which includes repetitive patterns of behaviour that influences how a person perceives and socializes with others, causing problems in communication and social interaction (Faras et al. 2010). ASD has been reported to be associated with GIT problems, such as overgrowth of intestinal pathogenic bacteria, abnormal gastrointestinal fistula, indigestion, and poor absorption in children (Fond et al. 2015). Alterations in the composition of the gut microbiota and its metabolites have been demonstrated both in ASD children and animal models of ASD Kushak et al. 2016). ...
... Anyhow, the enterotype can be translated as the "stratification" of the gut microbiota, which gives at the same time particularity of the microbial community for each individual (52). Besides the role played in food and drug digestion, intestinal microbiota have an essential physiological role in motility, IS development (mucosal and systemic), water and fat absorption and distribution, xenobiotic metabolism, and biosynthesis of vitamin K and SCFAs (19,(53)(54)(55)(56)(57). SCFAs seem to have an important role in mediating gut-brain interactions owing to their neuroactive properties and their effects on other gut-brain signaling pathways including the IS and ES (58). ...
Article
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Over the last 10 years, there has been a growing interest in the relationship between gut microbiota, the brain, and neurologic-associated affections. As multiple preclinical and clinical research studies highlight gut microbiota’s potential to modulate the general state of health state, it goes without saying that gut microbiota plays a significant role in neurogenesis, mental and cognitive development, emotions, and behaviors, and in the progression of neuropsychiatric illnesses. Gut microbiota produces important biologic products that, through the gut-brain axis, are directly connected with the appearance and evolution of neurological and psychiatric disorders such as depression, anxiety, bipolar disorder, autism, schizophrenia, Parkinson’s disease, Alzheimer’s disease, dementia, multiple sclerosis, and epilepsy. This study reviews recent research on the link between gut microbiota and the brain, and microbiome’s role in shaping the development of the most common neurological and psychiatric illnesses. Moreover, special attention is paid to the use of probiotic formulations as a potential non-invasive therapeutic opportunity for prevention and management of neuropsychiatric-associated affections.
... Saccharomyces, Escherichia, and Ba cillus secrete norepinephrine; Streptococcus, Entero coccus, Candida, and Escherichia secrete serotonin, whereas Serratia and Bacillus have the potential to secrete dopamine. All these neurotransmitters are known to play a crucial role in mental health (Fond et al., 2015). On the other hand, it is still unclear whether probiotics have a beneficial role in the brain function of healthy elderly (Sharon et al., 2016). ...
Article
Full-text available
The gastrointestinal (GI) microbiota is one of the most complex ecosystems in nature that are mainly comprised of bacteria and other microbes like fungi, protozoa, and viruses. More than 1000 bacterial species have been reported in the gut microbiome, of which most of these species belong to Firmicutes (31.1%), Proteobacteria (29.5%), Actinobacteria (25.9%), or Bacteroidetes (7.1%) phylum. A symbiotic relationship, which plays a critical role in host health, exists between intestinal microflora and its host. With aging, the intestinal microbiota profile changes are observed, generally characterized by the decrease in biodiversity, carriage of commensals, and enrichment of opportunistic pathogens. The dysbiosis associated with aging in the gut microbiota increases the risk of several diseases. Probiotics are defined as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host" and play crucial functions in improving gut health and disease in all age groups, particularly the elderly induvial. This review focuses on the promising effects of probiotics on slowing down the aging process, treating age-related diseases, and improving the quality of life in light of the current clinical studies.
... A further example of the involvement of gut microbiome-eCBome interactions in central neuroinflammatory disorders is depression. Among other psychiatric disorders, depression is indeed associated with dysbiosis, intestinal inflammation and loss of gut integrity [176,177]. In particular, in a mouse model of antimicrobial cocktail-induced dysbiosis, depressive behaviors and reduced social recognition memory as well as increased of gut inflammation were observed [178]. ...
Article
Full-text available
There is growing evidence that perturbation of the gut microbiome, known as “dysbiosis”, is associated with the pathogenesis of human and veterinary diseases that are not restricted to the gastrointestinal tract. In this regard, recent studies have demonstrated that dysbiosis is linked to the pathogenesis of central neuroinflammatory disorders, supporting the existence of the so-called microbiome-gut-brain axis. The endocannabinoid system is a recently recognized lipid signaling system and termed endocannabinoidome monitoring a variety of body responses. Accumulating evidence demonstrates that a profound link exists between the gut microbiome and the endocannabinoidome, with mutual interactions controlling intestinal homeostasis, energy metabolism and neuroinflammatory responses during physiological conditions. In the present review, we summarize the latest data on the microbiome-endocannabinoidome mutual link in health and disease, focalizing the attention on gut dysbiosis and/or altered endocannabinoidome tone that may distort the bidirectional crosstalk between these two complex systems, thus leading to gastrointestinal and metabolic diseases (e.g., idiopathic inflammation, chronic enteropathies and obesity) as well as neuroinflammatory disorders (e.g., neuropathic pain and depression). We also briefly discuss the novel possible dietary interventions based not only on probiotics and/or prebiotics, but also, and most importantly, on endocannabinoid-like modulators (e.g., palmitoylethanolamide) for intestinal health and beyond.
... The LDA threshold is set to 2, and one against all (less strict) is selected for multi group comparison. stress on gut microbiota (Fond et al., 2015). Probiotics are not only related to the production of SCFAs (Pane et al., 2018) but have also been shown to reduce the mRNA expression of the GABA receptor and c-fos in the brain by regulating the gut-brain axis via the vagus nerve pathway regulate brain function and stress state Molina-Torres et al., 2019). ...
... Due to the fast and demanding lifestyle, most of the individuals experience chronic stress, depression and anxiety in early life (Burokas et al. 2014;Caspi et al. 2003;Kendler et al. 2000). The major role in the regulation of mood, anxiety and stress is played by microbiota which was proved by animal studies (Fond et al. 2015). Grigoleit et al. (2011) conducted an experiment using endotoxin lipopolysaccharide, which when administered into healthy individuals results in increased levels of pro-inflammatory cytokines, salivary cortisol and plasma norepinephrine and exaggerated anxiety and depression. ...
Chapter
Microbial colonization commences during birth, and establishment of stable gut microbiota takes place in the first 3–5 years of life. A diverse group of microbiome including virome, facultative anaerobic bacteria (Proteobacteria), microaerophilic bacteria (Lactobacillus) and anaerobic bacteria (Bifidobacterium and Bacteroides) colonize the intestine. The gut comes across various different types of components like diet, allergens, microbial toxins and infectious agents and its interactions with endocrine, circulatory, neural and immune systems resulting in host physiological responses. The autonomic nervous system (NS) and the enteric NS play an important role in the neural control of gastrointestinal function. Probiotics are live microbes, which while administered in adequate amounts provide a benefit to their host. The usage of probiotics along with prebiotics improves intestinal health. In this chapter, we discuss probiotic intervention for the management/control of behaviour disorders of the microbiota-gut-brain axis.
... Moreover, microbiota and its metabolites have been suggested to be involved in the modulation of brain functions, such as emotional behaviors [3] stress-related responsiveness [4], pain [5], and food intake [6]. Consequently, alterations of the ''healthy" microbiota, referred to as dysbiosis, might drive functional and behavioral changes in animals and humans [7,8]. ...
Article
Full-text available
‘Dysbiosis’ of the adult gut microbiota, in response to challenges such as infection, altered diet, stress, and antibiotics treatment has been recently linked to pathological alteration of brain function and behavior. Moreover, gut microbiota composition constantly controls microglia maturation, as revealed by morphological observations and gene expression analysis. However, it is unclear whether microglia functional properties and crosstalk with neurons, known to shape and modulate synaptic development and function, are influenced by the gut microbiota. Here, we investigated how antibiotic-mediated alteration of the gut microbiota influences microglial and neuronal functions in adult mice hippocampus. Hippocampal microglia from adult mice treated with oral antibiotics exhibited increased microglia density, altered basal patrolling activity, and impaired process rearrangement in response to damage. Patch clamp recordings at CA3-CA1 synapses revealed that antibiotics treatment alters neuronal functions, reducing spontaneous postsynaptic glutamatergic currents and decreasing synaptic connectivity, without reducing dendritic spines density. Antibiotics treatment was unable to modulate synaptic function in CX3CR1-deficient mice, pointing to an involvement of microglia–neuron crosstalk through the CX3CL1/CX3CR1 axis in the effect of dysbiosis on neuronal functions. Together, our findings show that antibiotic alteration of gut microbiota impairs synaptic efficacy, suggesting that CX3CL1/CX3CR1 signaling supporting microglia is a major player in in the gut–brain axis, and in particular in the gut microbiota-to-neuron communication pathway.
... Studies found that under stress conditions, probiotics can play a beneficial role by regulating the synthesis and release of a variety of neurotransmitters and bioactive factors including cortisol , serum corticotropin-releasing factor (CRF) (Yang et al., 2016), tumor necrosis factor-α (TNF-α) (Marcos et al., 2004), and to some extent improve the stress-related physical and psychiatric symptoms of the subjects Langkamp-Henken et al., 2015), which is expected to become a potential therapy or auxiliary measure for relieving stress. However, some studies have found that effects of probiotics on cognition and stress resilience in humans are scarce and sometimes contradictory, and there is currently no evidence-based medical evidence of stress-relieving effect for probiotics, so we conducted a systematic review and meta-analysis for the data from all randomized controlled trials conducted in healthy subjects to date, focusing on whether probiotics alleviate the psychological/physiological stress of healthy subjects, and the possible adverse effects of probiotics, which are also important difference between our study and other systematic reviews and meta-analysis of the potential effects of probiotics on K E Y W O R D S gastrointestinal microbiome, healthy volunteers, meta-analysis, probiotics, psychological stress, systematic review mental illness (Fond et al., 2015;Huang, Wang, & Hu, 2016;Liu et al., 2018;Ng, Peters, Ho, Lim, & Yeo, 2018;Pirbaglou et al., 2016;Reis, Ilardi, & Punt, 2018;Wallace & Milev, 2017). ...
Article
Full-text available
Background Probiotics seems to play a beneficial role in stressed populations; thus, a systematic review and meta‐analysis to assess the effects of probiotics on stress in healthy subjects were conducted. Methods Randomized controlled trials on the effects of probiotics on stress in healthy subjects were retrieved from five databases. The effects of probiotics on subjective stress level, stress‐related subthreshold anxiety/depression level, cortisol level, and adverse reactions were analyzed. Separate subgroup analyses were conducted on single‐strain probiotics versus multi‐strain probiotics, and short‐term administration versus long‐term administration. Results Seven studies were included, involving a total of 1,146 subjects. All the studies were rated as low or moderate risk of bias. Our research found that probiotic administration can generally reduce the subjective stress level of healthy volunteers and may improve their stress‐related subthreshold anxiety/depression level, but no significant effect was observed in the subgroup analysis. The effect of probiotics on cortisol level was not significant. Adverse reactions were reported in only one of seven studies, but left undescribed. Conclusion Current evidence suggests that probiotics can reduce subjective stress level in healthy volunteers and may alleviate stress‐related subthreshold anxiety/depression level, without significant effect on cortisol level, and there is not enough support to draw conclusions about adverse effects; thus, more reliable evidence from clinical trials is needed.
... The clinical studies for schizophrenia tend to be restricted and based on nutrition and probiotics, also utilizing antipsychotics (Fond et al., 2015). Dietary adjustments can influence both the intestinal microflora's composition and behaviour. ...
... mikrobiotę skóry, dróg moczowych, przewodu pokarmowego [4]. W ludzkim organizmie jest 10 razy więcej komórek prokariotycznych niż eukariotycznych [4,9]. Wszystkie bakterie, które znajdują się w błonach śluzowych człowieka ważą około 2 kg. ...
Chapter
Streszczenie: Depresja jest poważnym problemem zdrowotnym na świecie. Według WHO około 350 milionów ludzi cierpi z powodu tej choroby. Pomimo tak dużej częstości występowania złożony patomechanizm depresji wciąż wymaga wyjaśnienia. U osób z zaburzeniami psychicznymi, obserwuje się podwyższone markery stanu zapalnego spowodowanego stresem, zaburzeniami składu bioty jelitowej lub infekcjami. Czynniki te powodują dysfunkcję bariery jelitowej, osłabiając połączenia ścisłe pomiędzy komórkami jelit, co może wywoływać translokację bakterii, której następstwem jest aktywacja układu odpornościowego i sekrecja cytokin prozapalnych. Ponadto cytokiny zmniejszają stężenie serotoniny, poprzez aktywację jej transporterów lub wpływ na szlak metaboliczny tryptofanu (Trp), którego metabolity mogą przyczyniać się do wystąpienia zaburzeń psychicznych. Zmiany składu mikrobioty jelitowej powodują również antybiotykoterapia oraz dieta. Celem tego rozdziału jest przedstawienie roli mikrobioty jelitowej w patofizjologii depresji oraz możliwości profilaktyki i leczenia. Kuracja prebiotykami i modyfikacja żywienia mogą pozytywnie wpłynąć na skład bakterii w jelitach, co obniża liczbę przypadków dysfunkcji bariery jelitowej i stanów zapalnych. Słowa kluczowe: mikrobiota jelitowa, depresja, stan zapalny, żywienie. Abstract: Depression is a major global problem, with the disease affecting approximately 350 million people according to WHO data. Despite its high prevalence, the complex pathomechanism of depression still requires to be elucidated. People with mental disorders exhibit increased pro-inflammatory markers induced by stress, the abnormal composition of gut microbiota or infections. These factors can cause the intestinal barrier dysfunction and impair tight junctions between enterocytes, which can in turn trigger the translocation of bacteria, followed by activation of the immune system and the secretion of pro-inflammatory cytokines. In addition, cytokines reduce the level of serotonin through the activation of serotonin transporters or their impact on the metabolic pathway of tryptophan (Trp). In turn, products of Trp metabolism may contribute to the occurrence of mental disorders. Both, an antibiotic therapy as well as a diet, can cause changes in the composition of gut microbiota. The aim of this chapter is to present the role of intestinal microbiota in the pathophysiology of depression and the possibilities of prevention and treatment. Prebiotic treatment and dietary modification can positively affect the composition of gut microbiota which can, in consequence, decrease the number of cases of intestinal barrier dysfunction and inflammation.
... Moreover, microbiota and its metabolites have been suggested to be involved in the modulation of brain functions, such as emotional behaviors [3] stress-related responsiveness [4], pain [5], and food intake [6]. Consequently, alterations of the "healthy" microbiota, referred to as dysbiosis, might drive functional and behavioral changes in animals and humans [7,8]. ...
Preprint
‘Dysbiosis’ of the adult gut microbiota, in response to challenges such as infection, altered diet, stress, and antibiotics treatment has been recently linked to pathological alteration of brain func-tion and behavior. Moreover, gut microbiota composition constantly controls microglia matura-tion as revealed by morphological observations and gene expression analysis. However, it is un-clear whether gut microbiota influences microglia functional properties and crosstalk with neu-rons, known to shape and modulate synaptic development and function. Here, we investigated how antibiotic mediated alteration of the gut microbiota influences microglial and neuronal functions in adult mice hippocampus. Hippocampal microglia from adult mice treated with oral antibiotics exhibited increased microglia density, altered basal patrolling activity, and impaired process rearrangement in response to damage. Patch clamp recordings at CA3-CA1 synapses revealed that antibiotics treatment alters neuronal functions, reducing spontaneous postsynaptic glutamatergic currents and decreasing synaptic connectivity, without reducing dendritic spines density. The effect of dysbiosis on neuronal functions are mediated by microglia-neuron cross-talk through the CX3CL1-CX3CR1 axis, as antibiotics treatment of CX3CR1 deficient mice, mod-ulates microglia density and processes rearrangement leaving unaltered synaptic function. To-gether, our findings show that the antibiotics alteration of gut microbiota impairs synaptic effi-cacy, probably through CX3CL1-CX3CR1 signaling supporting microglia as a major player in in the gut-brain axis, and in particular in the gut microbiota-to-neuron communication pathway.
Article
Full-text available
Modern approaches to management of medical conditions are based on a holistic view, taking into account bidirectional connections between physical and mental health. The current pharmacologically focused model has so far provided modest benefits in addressing the burden of poor mental health. Convincing data suggest that diet quality and select nutrient-based supplements might influence a range of neurochemical modulatory activities, improving the management of mental disorders. Examples of these nutrient-based supplements include omega-3 fatty acids, S-adenosyl methionine, N-acetyl cysteine, zinc, B vitamins (including folic acid), and vitamin D. The traditional Mediterranean diet is considered to be the most beneficial diet in our region. Based on the results of preclinical studies, we are increasingly aware of the role of intestinal microbiota in the pathogenesis and potential treatment of mental disorders. Bidirectional signalling between the brain and the gut microbiome involving vagal neurocrine and endocrine signalling mechanisms influences mental and physical wellbeing. These findings suggest that using prebiotics, probiotics or in the strict sense psychobiotics, as well as incorporating fermented foods in the diet, could have a potential role in the management of mental disorders. As of now, we lack sufficient evidence to implement recommendations for dietary supplements in treatment guidelines, however, this might change in light of emerging data from contemporary research studies, at least for certain indications. Citirajte kot/Cite as: Plemenitaš a. [Nutrition and dietary supplements in psychiatric diseases]. Zdrav Vestn. 2018;87(1-2):81-90.
Chapter
The bacteria in the gastrointestinal tract which forms the gut microbiome plays a vital role in maintaining body homeostasis and health of the host. Any change in the normal gut microbiome composition and function imposes gut dysbiosis, defined as an imbalance of the bacteria in the gut. The central nervous system (CNS) and the gut microbiome are in constant bidirectional communication involving endocrine, neuronal, and immunological mechanisms forming the gut–brain axis (GBA). Emerging preclinical studies suggest that gut dysbiosis may result in GBA dysfunction leading to neurodegenerative and neurodevelopmental diseases, as well as age-related cognitive decline. Therefore, modulation of gut microbiota composition and functionality offers a promising tool for treating or managing gut dysbiosis and in turn achieving a healthy gut–brain axis. Use of prebiotics is gaining attention as the most robust and safe method of achieving such modulation. Prebiotics refer to non-digestible food ingredients predominately some fermentable carbohydrates that can selectively modulate the composition and/or activity of the microbiota of the gut, thus conferring beneficial physiological effects on the host. The metabolism of prebiotics by the gut microbiome induces changes in the gut barrier integrity and promotes the release of metabolites (mainly SCFAs) contributing to the improvement of host health, particularly in the context of GBA. In this chapter, we discuss the concept of prebiotics, microbiota modulation by prebiotics, and the impact prebiotics on GBA.
Book
This second edition volume expands on the previous edition with updates to chapters and new chapters discussing the latest research in neuropsychiatric diseases. The chapters in this book are organized into eleven sections and cover the diversity and utility of animal models of psychiatric disorders, their development, modeling, and pathophysiological and molecular profiles. Part One looks at experimental modeling of neuropsychiatric studies and the usefulness and need of animal models. Parts Two and Three focus on experimental models of neuropsychiatric illnesses, including self-injurious behavior, bipolar disorder, anxiety, and learning and decision-making testing. Parts Four and Five discuss animal models of substance abuse. Part Six describes protocols to examine animal models related to maladaptive eating habits and behaviors. Parts Seven and Eight cover neurodegenerative diseases stemming from natural causes (aging), abnormal genetic backgrounds, or those brought on by trauma. Part Nine talks about inflammatory and metabolic alteration profiles relevant to autism spectrum disorders and depression. Parts Ten and Eleven conclude the book with a discussion on genetics, epigenetics, and system biology in the field of psychiatric disorders. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, Psychiatric Disorders: Methods and Protocols, Second Edition is a useful resource for graduates, postdoctoral workers, and established scientists working in the fields of behavioral and molecular neuropsychiatric research.
Article
The gut microbiota plays a crucial role in the development of the immune system and confers benefits or disease susceptibility to the host. Emerging studies have indicated that the gut microbiota could affect pulmonary health and disease through cross-talk between the gut microbiota and the lungs. Gut microbiota dysbiosis could lead to acute or chronic lung disease, such as asthma, tuberculosis and lung cancer. In addition, the composition of the gut microbiota may be associated with different lung diseases, the prevalence of which also vary by age. Modulation of the gut microbiota through short-chain fatty acids, probiotics and micronutrients may present potential therapeutic strategies to protect against lung diseases. In this review, we will provide an overview of the cross-talk between the gut microbiota and the lungs as well as elucidate the underlying pathogenesis or potential therapeutic strategies of some lung diseases from the point of view of the gut microbiota.
Chapter
Accumulating evidence suggests that microbiota are involved in the physiology and pathology and have implications in health and disease. The role of microbiota in various physiological processes, including the immune system and brain function, is well established. A great deal of studies has suggested the role of gut microbes in the brain’s physiology and pathology. The maturation and development of the human central nervous system (CNS) are regulated by both intrinsic and extrinsic factors, including microbiota. Studies mostly from germ-free animals or animals treated with broad-spectrum antibiotics show that specific microbiota can impact CNS physiology and neurochemical processes. The germ-free mice show neurological deficiencies in learning, memory, recognition, and emotional behaviors. Levels of the essential neurotransmitters such as serotonin, N-methyl-d-aspartate, and brain-derived neurotrophic factor are different from those in commonly grown mice. In humans, evidence for interplay between gastrointestinal pathology and neuropsychiatric conditions was presented in anxiety, depression, and autism. The gut microbiota was involved in the development and homeostasis of CNS in various pathways. In this chapter the roles of microbiota and development and function of the nervous system, gut–brain interactions, neurodegeneration, and potential approaches for treating CNS disorders will be discussed.
Chapter
Schizophrenia and bipolar disorder are severe mental disorders, both placing a significant burden on individuals’ wellbeing and global health generally. The complex interaction of multiple mechanisms, underlying these disorders, still needs further elucidation. Increased activation of components of the immune system may be involved, including alterations in intestinal permeability and the gut microbiome. Probiotics, defined as living microorganisms conferring health benefits to the host when administered in adequate amounts, may have some supportive therapeutic effect in psychiatric disorders.
Article
Full-text available
Traumatic brain injury (TBI) is a damage to the brain from an external force that results in temporary or permanent impairment in brain functions. Unfortunately, not many treatment options are available to TBI patients. Therefore, knowledge of the complex interplay between gut microbiome (GM) and brain health may shed novel insights as it is a rapidly expanding field of research around the world. Recent studies show that GM plays important roles in shaping neurogenerative processes such as blood-brain-barrier (BBB), myelination, neurogenesis, and microglial maturation. In addition, GM is also known to modulate many aspects of neurological behavior and cognition; however, not much is known about the role of GM in brain injuries. Since GM has been shown to improve cellular and molecular functions via mitigating TBI-induced pathologies such as BBB permeability, neuroinflammation, astroglia activation, and mitochondrial dysfunction, herein we discuss how a dysbiotic gut environment, which in fact, contributes to central nervous system (CNS) disorders during brain injury and how to potentially ward off these harmful effects. We further opine that a better understanding of GM-brain (GMB) axis could help assist in designing better treatment and management strategies in future for the patients who are faced with limited options.
Article
Bulimia nervosa (BN) and binge eating disorder (BED) are both eating disorders (EDs) characterised by episodes of overeating in which large amounts of food are consumed in short periods. The aetiology of BN and BED is not fully understood. Psychological and social factors influence the development of BN and BED, but biological factors such as neurohormones that regulate hunger and satiety, or neurotransmitters responsible for mood and anxiety play a significant role in sustaining symptoms. Increasing numbers of studies confirm the relationship between the composition of intestinal microbiota and the regulation of appetite, mood, and body mass. In this manuscript, we will describe the mechanisms by which intestinal dysbiosis can play an important role in the aetiology of binge eating episodes based on current understanding. Understanding the two-way relationship between BN and BED and alterations in the intestinal microbiota suggest the utility of new treatment methods of these disorders aimed at improving the composition of the intestinal microflora.
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Given the importance of understanding the role of neuroinflammation in psychiatric illness, including its emergence and progression, it is of practical value to explore the available tools that noninvasively index neuroinflammatory markers in vivo. Various aspects of neuroinflammation can be probed by magnetic resonance imaging (MRI) measures. These aspects include water content accumulation (T2-weighted anatomical MRI, magnetization transfer imaging and diffusion MRI); blood–brain barrier dysfunction and cellular infiltration (contrast-enhanced anatomical MRI); and molecular/metabolic signatures of neuroinflammation (magnetic resonance spectroscopy). This chapter provides a nontechnical overview of these MRI measures, which have been applied to estimate putative neuroinflammatory processes in psychiatric illness.
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The micro-organisms residing within the gastrointestinal tract, namely gut microbiota, form a dynamic population proper of each individual, mostly composed by bacteria which co-evolved symbiotically with human species. The advances of culture-independent techniques allowed the understanding of the multiple functions of the gut microbiota in human physiology and disease, the latter often recognising a predisposing condition in an imbalanced intestinal microbial ecosystem (dysbiosis). A complex mutual interconnection between the central nervous system (CNS), the intestine and the gut microbiota, known as “microbiota-gut-brain axis”, has been hypothesized to play a pivotal role in maintaining central and peripheral functions, as well as mental health. Thus, dysbiosis with specific microbiota imbalances seems to be strongly associated with the onset psychiatric disorders by altering neurodevelopment, enhancing neurodegeneration, affecting behaviour and mood. Fecal microbiota transplantation (FMT) consists of transferring the fecal matter from a donor into the gastrointestinal tract of a recipient, and it is used to quickly modulate the gut microbiota. This review focuses on the uses of FMT in psychiatric disorders. FMT has been used to induce dysbiosis and to study the disease development, or to heal dysbiosis-related mental disorders. Overall, FMT of impaired microbiota resulted effective in enhancing psychiatric-like disturbances (mainly depression and anxiety) in recipient animals, plausibly by impairing immune system, inflammatory and metabolic pathways, neurochemical processes and neuro-transmission. On the other side, preclinical and clinical data suggest that reversing or mitigating dysbiosis seems a promising strategy to restore behavioural impairments or to obtain psychiatric symptom relief. However, current evidence is limited by the lack of procedural standardization, the paucity of human studies in the vastity of psychiatric conditions and the need of a microbiota-targeted donor-recipient matching.
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Negative emotions and sleep disorders are common health-related concerns faced by many people who live under some sort of pressure in modern society. In the long run, these issues can decline the immunity of a person, which in turn is closely related to the inflammatory signaling pathway that affects the brain. Clinical evidence suggests that the intestinal flora can regulate the host’s sleep and emotional status through the brain intestinal axis. As a dietary factor, tea polyphenols (TP) play a role in regulating mood and sleep. On the one hand, the intestinal flora can promote the metabolism and absorption of TP in the body to thereby improve their bioavailability. On the other hand, TP can modify the abundance of intestinal flora, improve the composition of beneficial flora and inhibit the growth of harmful bacteria. Considering that the epidemiological causes of anxiety, depression and sleep disorders involve the interaction of environmental stress and genetic predisposition in various physiological systems, treatment options that combine the intestinal microbiota and TP may prove superior to the classical pharmacological treatments because intestinal microbiota promotes the production of a variety of bioactive metabolites from dietary polyphenols that can simultaneously regulate the moods and sleep to improve the immunity. In this review, we discussed the relationship among TP, intestinal flora, emotion and sleep, as well as their interactions that promote the effective regulation of emotion and sleep, to ultimately improve the body’s immunity.
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Suicide is a multifaceted phenomenon, related to an everlasting interconnection between biological, psychosocial, sociological, philosophical, and cultural aspects of human life. Immune system, which is constantly responding to changing environments and changing in response to them, seems to play a major role in this interaction. Multiple studies have reported increased risk of suicidal behaviours after or during inflammatory conditions. Individuals that engage in suicidal behaviours also have increased concentrations of inflammatory markers, such as interleukins 1β and 6, tumour necrosis factor α, and C-reactive protein, both in blood and the central nervous system (CNS). Stress, which is frequently mentioned among the major risk factors for suicidal behaviours, is also associated with a wide immune system dysregulation, entailing glucocorticoid system disruption and a low-grade inflammation. Mechanisms connecting systemic inflammation and CNS changes include damage to blood-brain barrier and interoceptive alterations, both resulting in changes in the communication between the periphery and the brain. Meanwhile, in CNS, pro-inflammatory cytokines may activate microglia causing a shift in tryptophan metabolism, preferentially generating cellular energy and toxic by-products of kynurenine pathway rather than serotonin. These changes in brain homeostasis lead to anatomical and functional brain alterations, most notably prefrontal cortex and insula, engendering maladaptive behavioural phenotypes, such as anhedonia and impulsivity that may mediate the association between inflammation and suicide. This chapter will provide a condensed overview of this complex association between inflammation and suicidal behaviours, presenting major findings in this area and explaining key pathways linking them.
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Le microbiote intestinal est un écosystème qui vit en symbiose avec l’organisme humain. Une perturbation de sa composition a des conséquences fonctionnelles pouvant entraîner et entretenir des pathologies. Son implication en santé mentale, notamment dans la physiopathologie de la dépression, fait l’objet d’études. Les pistes évoquées sont concluantes et méritent d’être approfondies pour dessiner, à l’avenir, une nouvelle approche thérapeutique des troubles dépressifs.
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The human gut harbors up to 100 trillion of microorganisms out of which only a few microorganisms could be considered as probiotics. The alteration in the gut microbial composition can cause a considerable effect on central physiology as well as act on behavioral or the physiological phenotype of an individual. Presently, various studies on probiotics have increased our interest in the role played by the brain–gut–microbiota axis in diverse neurodevelopmental disorders such as obesity, depression, and autism. Although the exact etiology and pathology of autism spectrum disorder (ASD) are not understood well; several studies indicate the link between gut microbiota and neurodevelopmental disorders in offspring, including ASD. Certain intestinal bacteria such as Clostridium and Sutterella genera have been reported in abundance in ASD condition, suggesting their crucial role in manifestation of ASD. Similarly, there are also preclinical evidences which mark that the supplementation of probiotics and/or prebiotics results in an improvement in behavior of the children with ASD. The chapter will discuss different mechanisms involved in manifestation and amelioration of ASD by gut microbiota and probiotics–prebiotics, respectively. Therefore the chapter will provide all the available preclinical and animal studies for depicting the current clinical picture of autism by representing the relationship between gut microbiota, probiotics, prebiotics, and their role in ASD.
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Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.
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Irritable bowel syndrome (IBS) has been associated with high prevalence of psychological disorders. However, it remains unclear whether IBS and each of its subtypes (predominant diarrhea IBS-D, constipation IBS-C, mixed IBS-M) are associated with higher anxiety and depressive symptoms levels. This study aimed to determine the associations of IBS and each of its subtypes with anxiety and/or depression. We conducted a systematic review and meta-analysis using five electronic databases (PubMed, PsychINFO, BIOSIS, Science Direct, and Cochrane CENTRAL). We selected case-control studies comparing anxiety and depression levels of patients with IBS to healthy controls, using standardized rating scales. Outcomes were measured as random pooled standardized mean differences (SMD). Ten studies were included in our analysis (885 patients and 1,384 healthy controls). Patients with IBS had significant higher anxiety and depression levels than controls (respectively, SMD = 0.76, 95 % CI 0.47; 0.69, p < 0.01, I2 = 81.7 % and SMD = 0.80, 95 % CI 0.42; 1.19, p < 0.01, I2 = 90.7 %). This significant difference was confirmed for patients with IBS-C and -D subtypes for anxiety, and only in IBS-D patients for depression. However, other IBS subtypes had a statistical trend to be associated with both anxiety and depressive symptomatology, which suggests a lack of power due to the small number of studies included. Patients with IBS had significantly higher levels of anxiety and depression than healthy controls. Anxiety and depression symptomatology should be systematically checked and treated in IBS patients, as psychological factors are important moderators of symptom severity, symptom persistence, decisions to seek treatment, and response to treatment.
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Interactions between the diet and intestinal microbiota play a role in health and disease, including obesity and related metabolic complications. There is great interest to use dietary means to manipulate the microbiota to promote health. Currently, the impact of dietary change on the microbiota and the host metabolism is poorly predictable and highly individual. We propose that the responsiveness of the gut microbiota may depend on its composition, and associate with metabolic changes in the host. Our study involved three independent cohorts of obese adults (n = 78) from Belgium, Finland, and Britain, participating in different dietary interventions aiming to improve metabolic health. We used a phylogenetic microarray for comprehensive fecal microbiota analysis at baseline and after the intervention. Blood cholesterol, insulin and inflammation markers were analyzed as indicators of host response. The data were divided into four training set - test set pairs; each intervention acted both as a part of a training set and as an independent test set. We used linear models to predict the responsiveness of the microbiota and the host, and logistic regression to predict responder vs. non-responder status, or increase vs. decrease of the health parameters. Our models, based on the abundance of several, mainly Firmicute species at baseline, predicted the responsiveness of the microbiota (AUC = 0.77-1; predicted vs. observed correlation = 0.67-0.88). Many of the predictive taxa showed a non-linear relationship with the responsiveness. The microbiota response associated with the change in serum cholesterol levels with an AUC of 0.96, highlighting the involvement of the intestinal microbiota in metabolic health. This proof-of-principle study introduces the first potential microbial biomarkers for dietary responsiveness in obese individuals with impaired metabolic health, and reveals the potential of microbiota signatures for personalized nutrition.
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Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.
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It is our contention that the concept of a probiotic as a living bacterium providing unspecified health benefits is inhibiting the development and establishment of an evidence base for the growing field of pharmacobiotics. We believe this is due in part to the current regulatory framework, lack of a clear definition of a probiotic, the ease with which currently defined probiotics can be positioned in the market place, and the enormous profits earned for minimum investment in research. To avoid this, we believe the following two actions are mandatory: international guidelines by a forum of stakeholders made available to scientists and clinicians, patient organizations, and governments; public research funds made available to the scientific community for performing independent rigorous studies both at the preclinical and clinical levels.
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OBJECTIVES: The clinical and economic burden of Clostridium difficile infection (CDI) is significant. Recurrent CDI management has emerged as a major challenge with suboptimal response to standard therapy. Fecal microbiota transplantation (FMT) has been used as a treatment to reconstitute the normal microbial homeostasis and break the cycle of antibiotic agents that may further disrupt the microbiome. Given the lack of randomized-controlled trials (RCTs) and limitations in previous systematic reviews, we aimed to conduct a systematic review with robust methods to determine the efficacy and safety profile of FMT in CDI.
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Establishing and maintaining beneficial interactions between the host and its associated microbiota are key requirements for host health. Although the gut microbiota has previously been studied in the context of inflammatory diseases, it has recently become clear that this microbial community has a beneficial role during normal homeostasis, modulating the host's immune system as well as influencing host development and physiology, including organ development and morphogenesis, and host metabolism. The underlying molecular mechanisms of host-microorganism interactions remain largely unknown, but recent studies have begun to identify the key signalling pathways of the cross-species homeostatic regulation between the gut microbiota and its host.
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The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder whose pathogenesis is not completely understood. Its high prevalence and the considerable effects on quality of life make IBS a disease with high social cost. Recent studies suggest that low grade mucosal immune activation, increased intestinal permeability and the altered host-microbiota interactions that modulate innate immune response, contribute to the pathophysiology of IBS. However, the understanding of the precise molecular pathophysiology remains largely unknown. In this study our objective was to evaluate the TLR expression as a key player in the innate immune response, in the colonic mucosa of IBS patients classified into the three main subtypes (with constipation, with diarrhea or mixed). TLR2 and TLR4 mRNA expression was assessed by real time RT-PCR while TLRs protein expression in intestinal epithelial cells was specifically assessed by flow cytometry and immunofluorescence. Mucosal inflammatory cytokine production was investigated by the multiplex technology. Here we report that the IBS-Mixed subgroup displayed a significant up-regulation of TLR2 and TLR4 in the colonic mucosa. Furthermore, these expressions were localized in the epithelial cells, opening new perspectives for a potential role of epithelial cells in host-immune interactions in IBS. In addition, the increased TLR expression in IBS-M patients elicited intracellular signaling pathways resulting in increased expression of the mucosal proinflammatory cytokines IL-8 and IL1β. Our results provide the first evidence of differential expression of TLR in IBS patients according to the disease subtype. These results offer further support that microflora plays a central role in the complex pathophysiology of IBS providing novel pharmacological targets for this chronic gastrointestinal disorder according to bowel habits.
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Alterations in intestinal microbiota composition are associated with several chronic conditions, including obesity and inflammatory diseases. The microbiota of older people displays greater inter-individual variation than that of younger adults. Here we show that the faecal microbiota composition from 178 elderly subjects formed groups, correlating with residence location in the community, day-hospital, rehabilitation or in long-term residential care. However, clustering of subjects by diet separated them by the same residence location and microbiota groupings. The separation of microbiota composition significantly correlated with measures of frailty, co-morbidity, nutritional status, markers of inflammation and with metabolites in faecal water. The individual microbiota of people in long-stay care was significantly less diverse than that of community dwellers. Loss of community-associated microbiota correlated with increased frailty. Collectively, the data support a relationship between diet, microbiota and health status, and indicate a role for diet-driven microbiota alterations in varying rates of health decline upon ageing.
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Caffeine is the most widely consumed psychoactive drug worldwide. Indeed the majority of adults consume caffeine on a daily basis, most commonly in the forms of coffee and tea. Coffee, in particular, is the favored caffeine source in the United States, where more than 150 million people drink coffee on a daily basis. Coffee, one of the richest sources of antioxidants in the average American's diet, contains caffeine and other antioxidants that have the potential to confer both beneficial and adverse health effects. A growing body of research shows that coffee drinkers, compared to nondrinkers, may be less likely to develop type 2 diabetes, stroke, depression, death from any cause, and neurodegenerative diseases, including Parkinson's and Alzheimer's. Coffee appears to have a neutral effect on cardiovascular health. Although more research is clearly needed, coffee, when consumed without added cream or sugar, is a calorie-free beverage that may confer health benefits, especially when used in individuals who do not have adverse subjective effects due to its stimulating effects, and when coffee is substituted for less healthy, unnatural, and/or high-calorie beverages, such as colas and other sugary and artificially sweetened sodas and soft drinks.
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Endotoxemia, characterized by an excess of circulating bacterial wall lipopolysaccharide, is associated with systemic inflammation and the metabolic syndrome. Placing 8 healthy subjects on a Western-style diet for 1 month induced a 71% increase in plasma levels of endotoxin activity (endotoxemia), whereas a prudent-style diet reduced levels by 31%. The Western-style diet might, therefore, contribute to endotoxemia by causing changes in gastrointestinal barrier function or the composition of the microbiota. Endotoxemia might also develop in individuals with gastrointestinal barrier impairment. Therapeutic reagents that reduce endotoxemia might reduce systemic inflammation in patients with gastrointestinal diseases or metabolic syndrome.
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The role of the gut microbiota in patho-physiology of irritable bowel syndrome (IBS) is suggested by several studies. However, standard cultural and molecular methods used to date have not revealed specific and consistent IBS-related groups of microbes. To explore the constipated-IBS (C-IBS) gut microbiota using a function-based approach. The faecal microbiota from 14 C-IBS women and 12 sex-match healthy subjects were examined through a combined strictly anaerobic cultural evaluation of functional groups of microbes and fluorescent in situ hybridisation (16S rDNA gene targeting probes) to quantify main groups of bacteria. Starch fermentation by C-IBS and healthy faecal samples was evaluated in vitro. In C-IBS, the numbers of lactate-producing and lactate-utilising bacteria and the number of H(2) -consuming populations, methanogens and reductive acetogens, were at least 10-fold lower (P < 0.05) compared with control subjects. Concomitantly, the number of lactate- and H(2) -utilising sulphate-reducing population was 10 to 100 fold increased in C-IBS compared with healthy subjects. The butyrate-producing Roseburia - E. rectale group was in lower number (0.01 < P < 0.05) in C-IBS than in control. C-IBS faecal microbiota produced more sulphides and H(2) and less butyrate from starch fermentation than healthy ones. A major functional dysbiosis was observed in constipated-irritable bowel syndrome gut microbiota, reflecting altered intestinal fermentation. Sulphate-reducing population increased in the gut of C-IBS and were accompanied by alterations in other microbial groups. This could be responsible for changes in the metabolic output and enhancement in toxic sulphide production which could in turn influence gut physiology and contribute to IBS pathogenesis.
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Paracellular permeability is determined by the complex structures of junctions that are located between the epithelial cells. Already in 1996, it was shown that the human probiotic strain Lactobacillus plantarum 299v and the rat-originating strain Lactobacillus reuteri R2LC could reduce this permeability in a methotrexate-induced colitis model in the rat. Subsequently, many animal models and cell culture systems have shown indications that lactobacilli are able to counteract increased paracellular permeability evoked by cytokines, chemicals, infections, or stress. There have been few human studies focusing on the effect of lactobacilli on intestinal paracellular permeability but recently it has been shown that they could influence the tight junctions. More precisely, short-term administration of L. plantarum WCSF1 to healthy volunteers increased the relocation of occludin and ZO-1 into the tight junction area between duodenal epithelial cells.
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Atypical antipsychotic drugs (AAPDs) such as olanzapine have a serious side effect profile including weight gain and metabolic dysfunction, and a number of studies have suggested a role for gender in the susceptibility to these effects. In recent times, the gut microbiota has been recognised as a major contributor to the regulation of body weight and metabolism. Thus, we investigated the effects of olanzapine on body weight, behaviour, gut microbiota and inflammatory and metabolic markers in both male and female rats. Male and female rats received olanzapine (2 or 4 mg/kg/day) or vehicle for 3 weeks. Body weight, food and water intake were monitored daily. The faecal microbial content was assessed by 454 pyrosequencing. Plasma cytokines (tumour necrosis alpha, interleukin 8 (IL-8), interleuin-6 and interleukin 1-beta (IL-1β)) as well as expression of genes including sterol-regulatory element binding protein-1c and CD68 were analysed. Olanzapine induced significant body weight gain in the female rats only. Only female rats treated with olanzapine (2 mg/kg) had elevated plasma levels of IL-8 and IL-1β, while both males and females had olanzapine-induced increases in adiposity and evidence of macrophage infiltration into adipose tissue. Furthermore, an altered microbiota profile was observed following olanzapine treatment in both genders. This study furthers the theory that gender may impact on the nature of, and susceptibility to, certain side effects of antipsychotics. In addition, we demonstrate, what is to our knowledge the first time, an altered microbiota associated with chronic olanzapine treatment.
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Unlabelled: Gastrointestinal disturbances are commonly reported in children with autism and may be associated with compositional changes in intestinal bacteria. In a previous report, we surveyed intestinal microbiota in ileal and cecal biopsy samples from children with autism and gastrointestinal dysfunction (AUT-GI) and children with only gastrointestinal dysfunction (Control-GI). Our results demonstrated the presence of members of the family Alcaligenaceae in some AUT-GI children, while no Control-GI children had Alcaligenaceae sequences. Here we demonstrate that increased levels of Alcaligenaceae in intestinal biopsy samples from AUT-GI children result from the presence of high levels of members of the genus Sutterella. We also report the first Sutterella-specific PCR assays for detecting, quantitating, and genotyping Sutterella species in biological and environmental samples. Sutterella 16S rRNA gene sequences were found in 12 of 23 AUT-GI children but in none of 9 Control-GI children. Phylogenetic analysis revealed a predominance of either Sutterella wadsworthensis or Sutterella stercoricanis in 11 of the individual Sutterella-positive AUT-GI patients; in one AUT-GI patient, Sutterella sequences were obtained that could not be given a species-level classification based on the 16S rRNA gene sequences of known Sutterella isolates. Western immunoblots revealed plasma IgG or IgM antibody reactivity to Sutterella wadsworthensis antigens in 11 AUT-GI patients, 8 of whom were also PCR positive, indicating the presence of an immune response to Sutterella in some children. Importance: Autism spectrum disorders affect ~1% of the population. Many children with autism have gastrointestinal (GI) disturbances that can complicate clinical management and contribute to behavioral problems. Understanding the molecular and microbial underpinnings of these GI issues is of paramount importance for elucidating pathogenesis, rendering diagnosis, and administering informed treatment. Here we describe an association between high levels of intestinal, mucoepithelial-associated Sutterella species and GI disturbances in children with autism. These findings elevate this little-recognized bacterium to the forefront by demonstrating that Sutterella is a major component of the microbiota in over half of children with autism and gastrointestinal dysfunction (AUT-GI) and is absent in children with only gastrointestinal dysfunction (Control-GI) evaluated in this study. Furthermore, these findings bring into question the role Sutterella plays in the human microbiota in health and disease. With the Sutterella-specific molecular assays described here, some of these questions can begin to be addressed.
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Fecal microbiota transplantation (FMT) has been utilized sporadically for over 50 years. In the past few years, Clostridium difficile infection (CDI) epidemics in the USA and Europe have resulted in the increased use of FMT, given its high efficacy in eradicating CDI and associated symptoms. As more patients request treatment and more clinics incorporate FMT into their treatment repertoire, reports of applications outside of CDI are emerging, paving the way for the use of FMT in several idiopathic conditions. Interest in this therapy has largely been driven by new research into the gut microbiota, which is now beginning to be appreciated as a microbial human organ with important roles in immunity and energy metabolism. This new paradigm raises the possibility that many diseases result, at least partially, from microbiota-related dysfunction. This understanding invites the investigation of FMT for several disorders, including IBD, IBS, the metabolic syndrome, neurodevelopmental disorders, autoimmune diseases and allergic diseases, among others. The field of microbiota-related disorders is currently in its infancy; it certainly is an exciting time in the burgeoning science of FMT and we expect to see new and previously unexpected applications in the near future. Well-designed and well-executed randomized trials are now needed to further define these microbiota-related conditions.
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Clinical and experimental evidence document that inflammation and increased peripheral cytokine levels are associated with depression-like symptoms and neuropsychological disturbances in humans. However, it remains unclear whether and to what extent cognitive functions like memory and attention are affected by and related to the dose of the inflammatory stimulus. Thus, in a cross-over, double-blind, experimental approach, healthy male volunteers were administered with either placebo or bacterial lipopolysaccharide (LPS) at doses of 0.4 (n = 18) or 0.8 ng/kg of body weight (n = 16). Pro- and anti-inflammatory cytokines, norephinephrine and cortisol concentrations were analyzed before and 1, 1.75, 3, 4, 6, and 24 h after injection. In addition, changes in mood and anxiety levels were determined together with working memory (n-back task) and long term memory performance (recall of emotional and neutral pictures of the International Affective Picture System). Endotoxin administration caused a profound transient physiological response with dose-related elevations in body temperature and heart rate, increases in plasma interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α and IL-1 receptor antagonist (IL-1ra), salivary and plasma cortisol, and plasma norepinephrine. These changes were accompanied by dose-related decreased mood and increased anxiety levels. LPS administration did not affect accuracy in working memory performance but improved reaction time in the high-dose LPS condition compared to the control conditon. In contrast, long-term memory performance was impaired selectively for emotional stimuli after administration of the lower but not of the higher dose of LPS. These data suggest the existence of at least two counter-acting mechanisms, one promoting and one inhibiting cognitive performance during acute systemic inflammation.
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Bidirectional signalling between the gastrointestinal tract and the brain is regulated at neural, hormonal, and immunological levels. This construct is known as the brain-gut axis and is vital for maintaining homeostasis. Bacterial colonization of the intestine plays a major role in the post-natal development and maturation of the immune and endocrine systems. These processes are key factors underpinning central nervous system (CNS) signaling. Recent research advances have seen a tremendous improvement in our understanding of the scale, diversity, and importance of the gut microbiome. This has been reflected in the form of a revised nomenclature to the more inclusive brain-gut-enteric microbiota axis and a sustained research effort to establish how communication along this axis contributes to both normal and pathological conditions. In this review, we will briefly discuss the critical components of this axis and the methodological challenges that have been presented in attempts to define what constitutes a normal microbiota and chart its temporal development. Emphasis is placed on the new research narrative that confirms the critical influence of the microbiota on mood and behavior. Mechanistic insights are provided with examples of both neural and humoral routes through which these effects can be mediated. The evidence supporting a role for the enteric flora in brain-gut axis disorders is explored with the spotlight on the clinical relevance for irritable bowel syndrome, a stress-related functional gastrointestinal disorder. We also critically evaluate the therapeutic opportunities arising from this research and consider in particular whether targeting the microbiome might represent a valid strategy for the management of CNS disorders and ponder the pitfalls inherent in such an approach. Despite the considerable challenges that lie ahead, this is an exciting area of research and one that is destined to remain the center of focus for some time to come.
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Gastrointestinal (GI) dysfunction has been reported in a substantial number of children with autism spectrum disorders (ASD). Activation of the mucosal immune response and the presence of abnormal gut microbiota are repeatedly observed in these children. In children with ASD, the presence of GI dysfunction is often associated with increased irritability, tantrums, aggressive behaviour, and sleep disturbances. Moreover, modulating gut bacteria with short-term antibiotic treatment can lead to temporary improvement in behavioral symptoms in some individuals with ASD. Probiotics can influence microbiota composition and intestinal barrier function and alter mucosal immune responses. The administration of probiotic bacteria to address changes in the microbiota might, therefore, be a useful novel therapeutic tool with which to restore normal gut microbiota, reduce inflammation, restore epithelial barrier function, and potentially ameliorate behavioural symptoms associated with some children with ASD. In this review of the literature, support emerges for the clinical testing of probiotics in ASD, especially in the context of addressing GI symptoms.
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The gut microbiota, which is considered a causal factor in metabolic diseases as shown best in animals, is under the dual influence of the host genome and nutritional environment. This study investigated whether the gut microbiota per se, aside from changes in genetic background and diet, could sign different metabolic phenotypes in mice. The unique animal model of metabolic adaptation was used, whereby C57Bl/6 male mice fed a high-fat carbohydrate-free diet (HFD) became either diabetic (HFD diabetic, HFD-D) or resisted diabetes (HFD diabetes-resistant, HFD-DR). Pyrosequencing of the gut microbiota was carried out to profile the gut microbial community of different metabolic phenotypes. Inflammation, gut permeability, features of white adipose tissue, liver and skeletal muscle were studied. Furthermore, to modify the gut microbiota directly, an additional group of mice was given a gluco-oligosaccharide (GOS)-supplemented HFD (HFD+GOS). Despite the mice having the same genetic background and nutritional status, a gut microbial profile specific to each metabolic phenotype was identified. The HFD-D gut microbial profile was associated with increased gut permeability linked to increased endotoxaemia and to a dramatic increase in cell number in the stroma vascular fraction from visceral white adipose tissue. Most of the physiological characteristics of the HFD-fed mice were modulated when gut microbiota was intentionally modified by GOS dietary fibres. The gut microbiota is a signature of the metabolic phenotypes independent of differences in host genetic background and diet.
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Diet strongly affects human health, partly by modulating gut microbiome composition. We used diet inventories and 16S rDNA sequencing to characterize fecal samples from 98 individuals. Fecal communities clustered into enterotypes distinguished primarily by levels of Bacteroides and Prevotella. Enterotypes were strongly associated with long-term diets, particularly protein and animal fat (Bacteroides) versus carbohydrates (Prevotella). A controlled-feeding study of 10 subjects showed that microbiome composition changed detectably within 24 hours of initiating a high-fat/low-fiber or low-fat/high-fiber diet, but that enterotype identity remained stable during the 10-day study. Thus, alternative enterotype states are associated with long-term diet.
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A consortium of researchers, advocates and clinicians announces here research priorities for improving the lives of people with mental illness around the world, and calls for urgent action and investment.
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The normal colonization of the mammalian intestine with commensal microbes is hypothesized to drive the development of the humoral and cellular mucosal immune systems during neonatal life and to maintain the physiologically normal steady state of inflammation in the gut throughout life. Neonatal conventionally reared mice and germ-free, deliberately colonized adult mice (gnotobiotic mice) were used to examine the efficacy of certain intestinal microbes.
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To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, approximately 150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively.
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Study how the dietary intake affects the fecal microbiota of a group of obese individuals after a 6-week very low-energy diet (VLED) and thereafter during a follow-up period of 5, 8, and 12 months. Additionally, we compared two different methods, fluorescent in situ hybridization (FISH) and real-time PCR (qPCR), for the quantification of fecal samples. Sixteen subjects participated in a 12-month dietary intervention which consisted of a VLED high in protein and low in carbohydrates followed by a personalized diet plan, combined with exercise and lifestyle counseling. Fecal samples were analyzed using qPCR, FISH, and denaturing gradient gel electrophoresis. The VLED affected the fecal microbiota, in particular bifidobacteria that decreased approximately two logs compared with the baseline numbers. The change in numbers of the bacterial groups studied followed the dietary intake and not the weight variations during the 12-month intervention. Methanogens were detected in 56 % of the participants at every sampling point, regardless of the dietary intake. Moreover, although absolute numbers of comparable bacterial groups were similar between FISH and qPCR measurements, relative proportions were higher according to FISH results. Changes in the fecal microbial numbers of obese individuals were primarily affected by the dietary intake rather than weight changes.
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The human large intestine contains a microbiota, the components of which are generically complex and metabolically diverse. Its primary function is to salvage energy from carbohydrate not digested in the upper gut. This is achieved through fermentation and absorption of the major products, short chain fatty acids (SCFA), which represent 40-50% of the available energy of the carbohydrate. The principal SCFA, acetate, propionate and butyrate, are metabolized by the colonic epithelium (butyrate), liver (propionate) and muscle (acetate). Intestinal bacteria also have a role in the synthesis of vitamins B and K and the metabolism of bile acids, other sterols and xenobiotics.
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Introduction: Toxoplasma gondii is the most common protozoan parasite in developed nations. Up to 43% of the French population may be infected, depending on eating habits and exposure to cats, and almost one third of the world human's population may be infected. Two types of infection have been described: a congenital form and an acquired form. Although the medical profession treats these latent cases as asymptomatic and clinically unimportant, results of animal studies and recent studies of personality profiles, behavior, and psychomotor performance have led to reconsider this assumption. Preclinical data: Among rats: parasite cysts are more abundant in amygdalar structures than those found in other regions of the brain. Infection does not influence locomotion, anxiety, hippocampal-dependent learning, fear conditioning (or its extinction) and neophobia in rats. Rats' natural predator is the cat, which is also T. gondii's reservoir. Naturally, rats have an aversion to cat urine, but the parasite suppresses this aversion in rats, thus influencing the infection cycle. Tachyzoites may invade different types of nervous cells, such as neurons, astrocytes and microglial cells in the brain, and Purkinje cells in cerebellum. Intracellular tachyzoites manipulate several signs for transduction mechanisms involved in apoptosis, antimicrobial effectors functions, and immune cell maturation. Dopamine levels are 14% higher in mice with chronic infections. These neurochemical changes may be factors contributing to mental and motor abnormalities that accompany or fol