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Abstract

The ability of gut microbiota to communicate with the brain and thus modulate behavior is emerging as an exciting concept in health and disease. The enteric microbiota interacts with the host to form essential relationships that govern homeostasis. Despite the unique enteric bacterial fingerprint of each individual, there appears to be a certain balance that confers health benefits. It is, therefore, reasonable to note that a decrease in the desirable gastrointestinal bacteria will lead to deterioration in gastrointestinal, neuroendocrine or immune relationships and ultimately disease. Therefore, studies focusing on the impact of enteric microbiota on the host and in particular on the central nervous system are essential to our understanding of the influence of this system. Recent studies published in this Journal demonstrate that germ-free mice display alterations in stress-responsivity, central neurochemistry and behavior indicative of a reduction in anxiety in comparison to conventional mice. Such data offer the enticing proposition that specific modulation of the enteric microbiota may be a useful strategy for stress-related disorders and for modulating the co-morbid aspects of gastrointestinal disorders such as irritable bowel syndrome and inflammatory bowel disease.

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... The gut microbiota plays an important role in the bidirectional interactions between the gut and brain. The microbiota-gut-brain axis involves multiple pivotal pathways, including the autonomic nervous system, the enteric nervous system, the neuroendocrine system, and the immune system [1,2]. The disturbance of the commensal gut microbiome not only causes many intestinal diseases but also impairs brain function, leading to neuropsychiatric disorders with abnormal behaviors [1,3]. ...
... The microbiota-gut-brain axis involves multiple pivotal pathways, including the autonomic nervous system, the enteric nervous system, the neuroendocrine system, and the immune system [1,2]. The disturbance of the commensal gut microbiome not only causes many intestinal diseases but also impairs brain function, leading to neuropsychiatric disorders with abnormal behaviors [1,3]. Studies conducted in humans and rodents have demonstrated the significant changes in gut microbiota composition between healthy individuals and those with psychological and emotional disorders [4,5]. ...
... No difference was found in IL-6, IL-2, IL-10, and IgG (p > 0.05) between the lines (Table 2). IgG (mg/mL) 1 IL-6 (pg/mL) 1 IL-2 (pg/mL) 1 IL-10 (pg/mL) 1 TNF-α (ng/mL) 1 The Faith phylogenetic distance was lower in line 63-hens than line 72-hens (p = 0.03, Figure 2A). The observed ASV, Shannon index and Pielou evenness did not differ between the line 63 and line 72 (p > 0.05, Figure 2B-D). ...
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The gut microbiota plays an important role in regulating brain function, influencing psychological and emotional stability. The correlations between conspecific aggression, gut microbiota, and physiological homeostasis were further studied in inbred laying chicken lines, 63 and 72, which were diversely selected for Marek’s disease, and they also behave differently in aggression. Ten sixty-week-old hens from each line were sampled for blood, brain, and cecal content. Neurotransmitters, cytokines, corticosterone, and heterophil/lymphocyte ratios were determined. Cecal microbiota compositions were determined by bacterial 16s rRNA sequencing, and functional predictions were performed. Our data showed that the central serotonin and tryptophan levels were higher in line 63 compared to line 72 (p < 0.05). Plasma corticosterone, heterophil/lymphocyte ratios, and central norepinephrine were lower in line 63 (p < 0.05). The level of tumor necrosis factor α tended to be higher in line 63. Faecalibacterium, Oscillibacter, Butyricicoccus, and Bacteriodes were enriched in line 63 birds, while Clostridiales vadin BB60, Alistipes, Mollicutes RF39 were dominated in line 72. From the predicted bacterial functional genes, the kynurenine pathway was upregulated in line 72. These results suggested a functional linkage of the line differences in serotonergic activity, stress response, innate immunity, and gut microbiota populations.
... The gut-brain axis or brain-gut axis (sometimes used interchangeably) is the biological link between the physiology and these emotions. It is described as a bidirectional communication system between the central nervous system (the brain and spinal cord) and the enteric nervous system [1]. In other words, it is the link between the brain's emotional and rational parts and our intestines' physiology and metabolism. ...
... Abnormal gut-brain axis activity has shown an association with physical and psychological illnesses. In the last decade, seminal work has demonstrated the importance of the gut microbiome and its influence on the system's functionality [1][2][3][4][5]. ...
... Moreover, both groups showed differences in their microbiota composition [5]. Furthermore, the co-occurrence of psychiatric disorders and gastrointestinal conditions have been linked to perturbations of the gut-brain axis systems [1]. For example, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) are typically presented with signs of psychiatric disorders such as anxiety, depression, somatization disorder, and/or bipolar disorder [46][47][48]. ...
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The gut–brain axis is the biological connection between the enteric and the central nervous systems. Given the expansion of the microbial sciences with the new human microbiome field facilitated by the decrease in sequencing costs, we now know more about the role of gut microbiota in human health. In this short review, particular focus is given to the gut–brain axis and its role in psychiatric diseases such as anxiety and depression. Additionally, factors that contribute to changes in the gut–brain axis, including the gut microbiome, nutrition, the host’s genome, and ethnic difference, are highlighted. Emphasis is given to the lack of studies on Hispanic populations, despite the fact this ethnic group has a higher prevalence of anxiety and depression in the US.
... The gut microbiota residing in the gastrointestinal (GI) tract plays an important role in the health status of the host by regulating the cells in local and distant organs, including the brain. Recent studies have demonstrated that the gut microbiota plays a critical role in the regulation of brain function and host immunity [1][2][3][4][5][6]. The biological network of bidirectional communication between the gut microbiota and the brain is referred to as the "microbiota-gut-brain axis" [5,7,8]. ...
... Recent studies have demonstrated that the gut microbiota plays a critical role in the regulation of brain function and host immunity [1][2][3][4][5][6]. The biological network of bidirectional communication between the gut microbiota and the brain is referred to as the "microbiota-gut-brain axis" [5,7,8]. A healthy gut microbiota benefits the host by producing microbial metabolites and neurotransmitters for communication with the host cells, such as intestinal epithelial cells (IECs) and immune cells. ...
... For example, infants with high levels of Bacteroides had better cognitive outcomes, while those who had high alpha diversity (the diversity of species within each individual) of gut microbiota showed lower scores on the overall composite score, visual reception scale, and expressive language scale [13]. Colonization of gut microbiota in early life plays an important role in the development and maturation of the immune and endocrine systems, both of which influence the central nervous system (CNS) function [2,5,6]. Studies on germ-free (GF) animals or broad-spectrum antibiotic-treated animals are commonly utilized to study the microbiota-gut-brain axis, particularly the impact of complete absence of the gut microbiota on development and behavior [2,16,17]. ...
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This review provides an overview of the importance of microbiota in the regulation of gut–brain communication in immune-related neurological disorders. The gastrointestinal (GI) tract hosts a diverse abundance of microbiota, referred to as gut microbiota. The gut microbiota plays a role in the maintenance of GI tract homeostasis and is likely to have multiple effects on brain development and function. The bidirectional communication between the gut microbiota and the brain is termed the microbiota–gut–brain axis. This communication between the intestine and the brain appears to affect human health and behavior, as certain animal studies have demonstrated the association between alterations in the gut microbiota and neurological disorders. Most insights about the microbiota–gut–brain axis come from germ-free animal models, which reveal the importance of gut microbiota in neural function. To date, many studies have observed the impact of the gut microbiota in patients with neurological disorders. Although many studies have investigated the microbiota–gut–brain axis, there are still limitations in translating this research to humans given the complexities of the relationship between the gut microbiota and the brain. In this review, we discuss emerging evidence of how the microbiota–gut–brain axis regulates brain development and function through biological networks, as well as the possible contribution of the microbiota–gut–brain axis in immune-related neurological disorders.
... The intestinal tract is the largest immune organ covered by mucosal epithelium; moreover, it is responsible for nutrient absorption. Furthermore, the intestinal tract is considered the second brain since the enteric nervous system autonomously controls gastrointestinal motility as well as the transport of water and electrolytes without requiring central control [6,7]. The bidirectional communication system between the brain and intestines is crucially involved in maintaining intestinal homeostasis and brain function [7,8]. ...
... Furthermore, the intestinal tract is considered the second brain since the enteric nervous system autonomously controls gastrointestinal motility as well as the transport of water and electrolytes without requiring central control [6,7]. The bidirectional communication system between the brain and intestines is crucially involved in maintaining intestinal homeostasis and brain function [7,8]. The intestinal microbial community influences this communication system through immune, endocrine, and neural pathways [9]. ...
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Mouse studies have reported anti-stress effects of Lactiplantibacillus plantarum SNK12 (SNK). Specifically, oral SNK administration increased mRNA levels of hippocampal neurotrophic factor and gamma-aminobutyric acid receptor in mice with sub-chronic mild stress-induced social defeat; moreover, it improved depressive behavior. We aimed to evaluate the efficacy of SNK ingestion against stress in healthy adults. We used the Uchida–Kraepelin test for the stress load, with a low-dose (50 mg/day), high-dose (150 mg/day), and placebo groups (dextrin). The primary outcome was the psychological evaluation as measured by the Profile of Mood States 2nd Edition (POMS2) using total mood disturbance (TMD) scores. The secondary outcomes were the score of each POMS2 item, salivary cortisol as a stress marker, and autonomic balance with the low frequency (LF)/ high frequency (HF) ratio. Compared with the placebo group, the SNK ingestion group showed significantly lower TMD scores. Additionally, compared with the placebo group, the high-dose group showed significantly lower scores for Tension-Anxiety and Confusion-Bewilderment, while the low-dose group showed significantly lower Anger-Hostility scores, salivary cortisol levels, and LF/HF scores. Our findings suggest that SNK ingestion could relieve stress (negative feelings, anxiety, tension, embarrassment, confusion, anger, and hostility) resulting from the temporary load caused by work and study.
... The human microbiome has been implicated in neuroinflammation in recent times. Changes in the microbiome, especially that of the human gut, can have subtle effects on the individual's brain cognitive capacity and behavior [5]. The changes in the activity of various brain regions in response to microbiome changes suggest that human microbiota and associated products are important determinants of neuronal coordination [6]. ...
... Owing to its neuromodulatory effects and its role in depression, anxiety, and stress response, the microbiome can serve to identify new drug candidates and techniques for treatment-resistant depression (TRD) [8,9]. Various probiotics have shown promising results in animal model studies for treating anxiety and depression [5]. Some probiotics have also been tested for their role in reducing depression and anxiety in human subjects [8,10]. ...
... Their genes and the molecules produced by the microorganisms (e.g., structural elements, metabolites, phages, viruses) are collectively called the microbiome (Berg et al., 2020). The microbiome connects many physiological systems (e.g., endocrine, immune, central nervous systems Garcia-Reyero, 2017;Cusick et al., 2021b) resulting in bidirectional, functional relationships with these systems (Collins and Bercik, 2014;Cryan and O'Mahony, 2011). These bidirectional relationships can influence a large variety of outcomes, from early development (Diaz et al., 2011;Erny et al., 2015), to immune system function , to behavior and survival (Williams et al., 2020). ...
... An individual's experiences during the prenatal period, including exposure to maternal stress (Seckl and Meaney, 2004;Duckworth et al., 2015) and the maternal microbiome (Dominguez-Bello et al., 2010) can have profound, long-term effects on offspring development, the foundation and development of offspring's microbiome, and offspring behavior. The HPA axis and the gut microbiome display bidirectional communication such that alterations in one system may affect the function of the other (Cryan and O'Mahony, 2011;Cryan et al., 2019;Cusick et al., 2021b). In this study, we investigated the interactive effects of maternal stress and manipulations of the maternal microbiome on offspring growth, gut microbiome composition and diversity, stress response, and social behavior. ...
Article
The gut microbiome, a community of commensal, symbiotic and pathogenic bacteria, fungi, and viruses, interacts with many physiological systems to affect behavior. Prenatal experiences, including exposure to maternal stress and different maternal microbiomes, are important sources of organismal variation that can affect offspring development. These physiological systems do not act in isolation and can have long-term effects on offspring development and behavior. Here we investigated the interactive effects of maternal stress and manipulations of the maternal microbiome on offspring development and social behavior using Siberian hamsters, Phodopus sungorus. We exposed pregnant females to either a social stressor, antibiotics, both the social stressor and antibiotics, or no treatment (i.e., control) over the duration of their pregnancy and quantified male and female offspring growth, gut microbiome composition and diversity, stress-induced cortisol concentrations, and social behavior. Maternal antibiotic exposure altered the gut microbial communities of male and female offspring. Maternal treatment also had sex-specific effects on aspects of offspring development and aggressive behavior. Female offspring produced by stressed mothers were more aggressive than other female offspring. Female, but not male, offspring produced by mothers exposed to the combined treatment displayed low levels of aggression, suggesting that alteration of the maternal microbiome attenuated the effects of prenatal stress in a sex-specific manner. Maternal treatment did not affect non-aggressive behavior in offspring. Collectively, our study offers insight into how maternal systems can interact to affect offspring in sex-specific ways and highlights the important role of the maternal microbiome in mediating offspring development and behavior.
... The human microbiome has been implicated in neuroinflammation in recent times. Changes in the microbiome, especially that of the human gut, can have subtle effects on the individual's brain cognitive capacity and behavior [5]. The changes in the activity of various brain regions in response to microbiome changes suggest that human microbiota and associated products are important determinants of neuronal coordination [6]. ...
... Owing to its neuromodulatory effects and its role in depression, anxiety, and stress response, the microbiome can serve to identify new drug candidates and techniques for treatment-resistant depression (TRD) [8,9]. Various probiotics have shown promising results in animal model studies for treating anxiety and depression [5]. Some probiotics have also been tested for their role in reducing depression and anxiety in human subjects [8,10]. ...
Article
The human gut microbiome has been implicated in a host of bodily functions and their regulation, including brain development and cognition. Neuroinflammation is a relatively newer piece of the puzzle and is implicated in the pathogenesis of many neurological disorders. The microbiome of the gut may alter the inflammatory signaling inside the brain through the secretion of short-chain fatty acids, controlling the availability of amino acid tryptophan and altering vagal activation. Studies in Korea and elsewhere highlight a strong link between microbiome dynamics and neurocognitive states, including personality. For these reasons, re-establishing microbial flora of the gut looks critical for keeping neuroinflammation from putting the whole system aflame through probiotics and allotransplantation of the fecal microbiome. However, the numerosity of the microbiome remains a challenge. For this purpose, it is suggested that wherever possible, a fecal microbial auto-transplant may prove more effective. This review summarizes the current knowledge about the role of the microbiome in neuroinflammation and the various mechanism involved in this process. As an example, we have also discussed the autism spectrum disorder and the implication of neuroinflammation and microbiome in its pathogenesis.
... Gut microbiota diversity has been strongly associated with mood-relating behaviors, such as depression (Lin et al., 2009;Winter et al., 2018). Accumulating evidences indicated that gut microbiota influenced central neurochemistry and behavior, which is called the microbiota-gut-brain axis (Cryan and O'Mahony, 2011;Dinan and Cryan, 2017). In the present study, we observed no significant difference in α-diversity (consisting of Shannon and Simpson indices) among the Sham, CMI + Dep, and CMI + Non-Dep groups. ...
Article
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Depression is common among patients who have chronic myocardial infarction (CMI). Despite their frequency, depression and CMI are bidirectional related conditions, each is a risk for the other, and they often co-exist, suggesting shared or interacting pathomechanisms. Accumulating data revealed the effects of gut microbiota in terms of regulating depression via the gut–brain axis. Thus, we investigated the role of gut microbial dysbiosis in CMI-induced depression-like behavior. Hierarchical cluster analysis of sucrose preference test (SPT) results was adopted to classify the CMI rats into depression-like behavior (CMI + Dep) or non-depression-like behavior (CMI + Non-Dep) phenotypes. First, 16S ribosomal RNA sequencing analysis showed both β-diversity and relative abundance of several gut bacteria significantly differed between the CMI + Dep and CMI + Non-Dep rats. Next, transplantation of fecal microbiota from CMI + Dep rats visibly altered the relative abundance of gut microbiota and also induced depression-like behavior in the antibiotics-treated pseudo-germ-free rats. In conclusion, these findings suggested that dysbiosis in gut microbial composition contributed to the onset of CMI-induced depression-like behavior and that exogenous regulation of gut microbiota composition could be a potential therapeutic strategy for CMI and related depression-like behavior.
... Dysbiosis of gut microbiota has been linked to metabolic disorders such as obesity, type 2 diabetes, and chronic inflammatory diseases such as psoriasis via the 'microbiome-gut-brain axis' and 'gut-skin axis' (Benhadou et al. 2018;Cryan and O'Mahony 2011;Wang et al. 2019). Wang et al. confirmed that gut microbiota-derived metabolites may play an important role in the pathogenesis of diseases and could interact with the host through several pathways (Wang et al. 2019). ...
Article
Psoriasis is an immune-mediated inflammatory skin disease associated with multiple comorbidities. Considered one of the most common inflammatory skin diseases among the general population, it not only affects the skin, but also negatively impacts other organs and joints. In addition, psoriasis has been associated with several chronic cardio-metabolic diseases such as obesity, which would seem to be (i) a risk factor for the onset of psoriasis and (ii) a worsening factor of the severity of the disease. Weight loss appears to improve severity in overweight patients. Recently proposed as an obesity management nutritional strategy, the very-low-calorie ketogenic diet (VLCKD) has demonstrated significant effects in reducing inflammatory processes. In the current review, we describe the evidence available on psoriasis and VLCKD, and provide a practical guide to the prescription of VLCKD in the different phases, evaluation and management of possible adverse events, and the importance of physical activity as a lifestyle modification to reduce psoriasis and associated comorbidities. Randomized control trials are, however, necessary to determine the most effective VLCKD protocol for patients with obesity and psoriasis, optimal protocol duration, composition of micronutrients and macronutrients, choice of special supplements, and management of carbohydrate reintroduction.
... On the other hand, gut microbes also regulate the availability of sex steroids in the gut environment, such as oestrogens [22][23][24][25][26][27] and androgens [26,28,29]. Microbiota and their derived metabolites actively participate in host homeostasis via the gut-brain axis, a bi-directional communication highway [26,[30][31][32][33][34], which includes immune, endocrine, neural, and humoral routes [31,35,36]. ...
Article
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Sex steroids, derived mainly from gonads, can shape microbiota composition; however, the impact of gonadectomy and sex on steroid production in the gut (i.e., gut steroids), and its interaction with microbiota composition, needs to be clarified. In this study, steroid environment and gut steroidogenesis were analysed by liquid chromatography tandem mass spectrometry and expression analyses. Gut microbiota composition as branched- and short-chain fatty acids were determined by 16S rRNA gene sequence analysis and gas chromatography flame ionisation detection, respectively. Here, we first demonstrated that levels of pregnenolone (PREG), progesterone (PROG), and isoallopregnanolone (ISOALLO) were higher in the female rat colon, whereas the level of testosterone (T) was higher in males. Sexual dimorphism on gut steroidogenesis is also reported after gonadectomy. Sex, and more significantly, gonadectomy, affects microbiota composition. We noted that a number of taxa and inferred metabolic pathways were associated with gut steroids, such as positive associations between Blautia with T, dihydroprogesterone (DHP), and allopregnanolone (ALLO), whereas negative associations were noted between Roseburia and T, ALLO, PREG, ISOALLO, DHP, and PROG. In conclusion, this study highlights the novel sex-specific association between microbiota and gut steroids with possible relevance for the gut-brain axis.
... Gastrointestinal comorbidities are prevalent in AD [70], but relatively few studies emphasize the connection between exercise and gut microbiota in AD. This complex mass of microbiota [71,72] contributes to several functions through neuronal, immune, endocrine, and metabolic pathways [73,74]. The genomes of all microorganisms can be helpful, but they are also potentially harmful to the human body. ...
Article
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Alzheimer’s disease (AD) is a progressive degenerative disorder and a leading cause of dementia in the elderly. The etiology of AD is multifactorial, including an increased oxidative state, deposition of amyloid plaques, and neurofibrillary tangles of the tau protein. The formation of amyloid plaques is considered one of the first signs of the illness, but only in the central nervous system (CNS). Interestingly, results indicate that AD is not just localized in the brain but is also found in organs distant from the brain, such as the cardiovascular system, gut microbiome, liver, testes, and kidney. These observations make AD a complex systemic disorder. Still, no effective medications have been found, but regular physical activity has been considered to have a positive impact on this challenging disease. While several articles have been published on the benefits of physical activity on AD development in the CNS, its peripheral effects have not been discussed in detail. The provocative question arising is the following: is it possible that the beneficial effects of regular exercise on AD are due to the systemic impact of training, rather than just the effects of exercise on the brain? If so, does this mean that the level of fitness of these peripheral organs can directly or indirectly influence the incidence or progress of AD? Therefore, the present paper aims to summarize the systemic effects of both regular exercise and AD and point out how common exercise-induced adaptation via peripheral organs can decrease the incidence of AD or attenuate the progress of AD.
... The gut microbiome could be the missing link in the conceptualization and treatment of psychological disorders [4]. The microbiome-gut-brain axis (MGBA) provides a network for signals from the brain to influence the motor, sensory, and secretory functions of the gut while simultaneously allowing signals and metabolites from the gut microbiome to influence brain development, biochemistry, function, and behavior [8][9][10]. ...
Article
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Background: Various neurocognitive and mental health-related conditions have been associated with the gut microbiome, implicating a microbiome-gut-brain axis (MGBA). The aim of this systematic review was to identify, categorize, and review clinical evidence supporting medicinal plants for the treatment of mental disorders and studies on their interactions with the gut microbiota. Methods: This review included medicinal plants for which clinical studies on depression, sleeping disorders, anxiety, or cognitive dysfunction as well as scientific evidence of interaction with the gut microbiome were available. The studies were reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Eighty-five studies met the inclusion criteria and covered thirty mental health-related medicinal plants with data on interaction with the gut microbiome. Conclusion: Only a few studies have been specifically designed to assess how herbal preparations affect MGBA-related targets or pathways. However, many studies provide hints of a possible interaction with the MGBA, such as an increased abundance of health-beneficial microorganisms, anti-inflammatory effects, or MGBA-related pathway effects by gut microbial metabolites. Data for Panax ginseng, Schisandra chinensis, and Salvia rosmarinus indicate that the interaction of their constituents with the gut microbiota could mediate mental health benefits. Studies specifically assessing the effects on MGBA-related pathways are still required for most medicinal plants.
... This bidirectional communication modulates the interaction between the brain and the gastrointestinal tract to maintain homeostasis and to create a more comprehensive concept called the "microbiota-gut-brain axis." [162]. ...
Article
Although oxidative agents such as free radicals can fight pathogens, an imbalance of oxidants to anti-oxidant activity can lead to harmful effects in our body known as oxidative stress. Various cellular organelles produce oxidative agents as well as anti-oxidants. The main oxidative stressors are classified under the free radical species; reactive oxygen species and reactive nitrogen species. On the other hand, super oxide dismutase, glutathione peroxidase, catalase and Glutathione are the main enzymatic mechanisms against oxidations. Gut microbiota with trillions of beneficial bacteria plays a considerable role in the production of anti-oxidants. Emerging evidence indicates an association between damaged intestinal flora and oxidative stress. Probiotics as beneficial bacteria are shown to restore damaged intestinal microbiota. Extensive evidence indicates the helpful effects of probiotics on the balance of anti-oxidant/oxidative agents. Since oxidative stressors play an important role in the development of some neurological disorders, intestinal microbiota modification and probiotic supplements are considered as suggested treatments to prevent or even relieve symptoms in the brain diseases. This review considers the beneficial effect of the gut and probiotic bacteria in either fighting the oxidative factors or producing the anti-oxidative biomarkers.
... Probiotics and prebiotics, which can promote the balance of gut microbiota, are of great interest as they also promote anxiety relief (Cryan and O'Mahony, 2011). Decreased anxietylike behavior and plasma corticosterone are observed after prebiotic treatment (fructo-oligosaccharides) in stressed mice (Burokas et al., 2017). ...
Article
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Depression and anxiety are devastating disorders. Understanding the mechanisms that underlie the development of depression and anxiety can provide new hints on novel treatments and preventive strategies. Here, we summarize the latest findings reporting the novel roles of gut microbiota and microRNAs (miRNAs) in the pathophysiology of depression and anxiety. The crosstalk between gut microbiota and the brain has been reported to contribute to these pathologies. It is currently known that some miRNAs can regulate bacterial growth and gene transcription while also modulate the gut microbiota composition, suggesting the importance of miRNAs in gut and brain health. Treatment and prevention strategies for neuropsychiatric diseases, such as physical exercise, diet, and probiotics, can modulate the gut microbiota composition and miRNAs expressions. Nonetheless, there are critical questions to be addressed to understand further the mechanisms involved in the interaction between the gut microbiota and miRNAs in the brain. This review summarizes the recent findings of the potential roles of microbiota and miRNA on the neuropathology of depression and anxiety, and its potential as treatment strategies.
... Factors such as diet, illness, drug, and infection may also change microbiota. [34][35][36] The term "gut-microbiota-brain axis" is defined as a bidirectional communication between the brain and gut bacterial community through multiple systems forming a network (Figure 1). It has a significant role in maintaining the homeostasis of the CNS and gastrointestinal system. ...
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Introduction: Obesity is a major health problem that is associated with many physiological and mental disorders, such as diabetes, stroke, and depression. Gut microbiota has been affirmed to interact with various organs, including the brain. Intestinal microbiota and their metabolites might target the brain directly via vagal stimulation or indirectly through immune-neuroendocrine mechanisms, and they can regulate metabolism, adiposity, homoeostasis and energy balance, and central appetite and food reward signaling, which together have crucial roles in obesity. Studies support the concept of bidirectional signaling within the gut-brain axis (GBA) in the pathophysiology of obesity, mediated by metabolic, endocrine, neural, and immune system mechanisms. Materials and methods: Scopus, PubMed, Google Scholar, and Web of Science databases were searched to find relevant studies. Results: The gut-brain axis (GBA), a bidirectional connection between the gut microbiota and brain, influences physiological function and behavior through three different pathways. Neural pathway mainly consists of the enteric nervous system (ENS) and vagus nerve. Endocrine pathway, however, affects the neuroendocrine system of the brain, particularly the hypothalamus-pituitary-adrenal (HPA) axis and immunological pathway. Several alterations in the gut microbiome can lead to obesity, by modulating metabolic pathways and eating behaviors of the host through GBA. Therefore, novel therapies targeting the gut microbiome, i.e., fecal microbiota transplantation and supplementation with probiotics and prebiotics, can be a potential treatment for obesity. Conclusion: This study corroborates the effect of gut microbiome on physiological function and body weight. The results show that the gut microbiota is becoming a target for new antiobesity therapies.
... We hypothesize that one such driving force may be the microbial flora associated with epithelia (microbiota) or, more specifically, the gut microbiota since the gut contains most of the microbes in mammals. Emerging evidence suggests that gut microbiota plays a pivotal role in brain neurodevelopment and behaviour via the socalled gut-brain axis (Cryan & O'Mahony, 2011). Indeed, studies in human and animal models have identified early postnatal microbial colonization prior to weaning as critical for healthy neurodevelopment, and disruption of colonization in the susceptible periods from weaning to adolescence has been linked to disturbances in brain signalling and neuropsychiatric disorders (Warner, 2019). ...
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μ‐opioid receptors (MOPr) play a critical role in social play, reward, and pain, in a sex and age‐dependent manner. There is evidence to suggest that sex and age differences in brain MOPr density may be responsible for this variability, however, little is known about the factors driving these differences in cerebral MOPr density. Emerging evidence highlights gut microbiota's critical influence and its bidirectional interaction with the brain on neurodevelopment. Therefore, we aimed to determine the impact of gut microbiota on MOPr density in male and female brains at different developmental stages. Quantitative [3H]DAMGO autoradiographic binding was carried out in the forebrain of male and female conventional (CON), and germ‐free (GF) rats at postnatal days (PND) 8, 22, and 116‐150. Significant 'microbiota status x sex,' 'age x brain region' interactions, and microbiota status‐ and age‐dependent effects on MOPr binding were uncovered. Microbiota status influenced MOPr levels in males but not females, with higher MOPr levels observed in GF vs. CON rats overall regions and age groups. In contrast, no overall sex differences were observed in GF or CON rats. Interestingly, within‐age planned comparison analysis conducted in frontal cortical and brain regions associated with reward revealed that this microbiota effect was restricted only to PND22 rats. Thus, this pilot study uncovers the critical sex‐dependent role of gut microbiota in regulating cerebral MOPr density, which is restricted to the sensitive developmental period of weaning. This may have implications in understanding the importance of microbiota during early development on opioid signalling and associated behaviours.
... Recent studies in the field of neuroscience and neuroimmunology [79,85] have revealed that the functional crosstalk between the gut microbiota and brain through GBA signaling is mediated by complex and multiple pathways. The top-to-bottom pathways from the brain to the gut influence sensory, motor, and secretory modalities of the GI tract [86,87], whereas the bottom-to-top signals from the gut to the brain impact cognitive and neurobehavioral functions [8,88]. The precise Cells 2022, 11, 1239 5 of 28 pathways involved in the GBA remain to be fully determined. ...
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Recent research on the gut microbiome has revealed the influence of gut microbiota (GM) on ischemic stroke pathogenesis and treatment outcomes. Alterations in the diversity, abundance, and functions of the gut microbiome, termed gut dysbiosis, results in dysregulated gut–brain signaling, which induces intestinal barrier changes, endotoxemia, systemic inflammation, and infection, affecting post-stroke outcomes. Gut–brain interactions are bidirectional, and the signals from the gut to the brain are mediated by microbially derived metabolites, such as trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs); bacterial components, such as lipopolysaccharide (LPS); immune cells, such as T helper cells; and bacterial translocation via hormonal, immune, and neural pathways. Ischemic stroke affects gut microbial composition via neural and hypothalamic–pituitary–adrenal (HPA) pathways, which can contribute to post-stroke outcomes. Experimental and clinical studies have demonstrated that the restoration of the gut microbiome usually improves stroke treatment outcomes by regulating metabolic, immune, and inflammatory responses via the gut–brain axis (GBA). Therefore, restoring healthy microbial ecology in the gut may be a key therapeutic target for the effective management and treatment of ischemic stroke.
... In hospitalized COVID-19 patients, intestinal dysbiosis was noted with decreased probiotics such as Lactobacillus and Bifidobacterium [68]. Several studies have demonstrated the communication between intestinal bacteria and the nervous system known as the microbiome-gut-brain axis [69][70][71][72][73]. Neufeld et. ...
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The ongoing pandemic resulting from severe acute respiratory syndrome—caused by coronavirus 2 (SARS-CoV-2)—has posed a multitude of healthcare challenges of unprecedented proportions. Intestinal enterocytes have the highest expression of angiotensin-converting enzyme-2 (ACE2), which functions as the key receptor for SARS-CoV-2 entry into cells. As such, particular interest has been accorded to SARS-CoV-2 and how it manifests within the gastrointestinal system. The acute and chronic alimentary clinical implications of infection are yet to be fully elucidated, however, the gastrointestinal consequences from non-SARS-CoV-2 viral GI tract infections, coupled with the generalized nature of late sequelae following COVID-19 disease, would predict that motility disorders are likely to be seen in these patients. Determination of the chronic effects of COVID-19 disease, herein defined as GI disease which is persistent or recurrent more than 3 months following recovery from the acute respiratory illness, will require comprehensive investigations comprising combined endoscopic- and motility-based evaluation. It will be fascinating to ascertain whether the specific post-COVID-19 phenotype is hypotonic or hypertonic in nature and to identify the most vulnerable target portions of the gut. A specific biological hypothesis is that motility disorders may result from SARS-CoV-2-induced angiotensin-converting enzyme 2 (ACE2) depletion. Since SARS-CoV-2 is known to exhibit direct neuronal tropism, the potential also exists for the development of neurogenic motility disorders. This review aims to explore some of the potential pathophysiologic mechanisms underlying motility dysfunction as it relates to ACE2 and thereby aims to provide the foundation for mechanism-based potential therapeutic options.
... The brain-gut axis, which is linked by the immune system, is closely associated with mental disease and neurodevelopmental disorders (94). The mechanism underlying the influence of the intestinal barrier and intestinal flora on brain function may include synapse formation regulation (95), neuronal signaling activation, ROS formation inhibition (96), and blood-brain barrier function regulation via secondary metabolites (97). ...
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Acrylamide (ACR), a potential neurotoxin, is produced by the Maillard reaction between reducing sugars and free amino acids during food processing. Over the past decade, the neurotoxicity of ACR has caused increasing concern, prompting many related studies. This review summarized the relevant literature published in recent years and discussed the exposure to occupational, environmental, and daily ACR contamination in food. Moreover, ACR metabolism and the potential mechanism of ACR-induced neurotoxicity were discussed, with particular focus on the axonal degeneration of the nervous system, nerve cell apoptosis, oxidative stress, inflammatory response, and gut-brain axis homeostasis. Additionally, the limitations of existing knowledge, as well as new perspectives, were examined, specifically regarding the connection between the neurotoxicity caused by ACR and neurodegenerative diseases, NOD-like receptor protein 3 (NLRP3) inflammasome-related neuroinflammation, and microbiota-gut-brain axis signaling. This review might provide systematic information for developing an alternative pathway approach to assess ACR risk.
... In addition, several animal studies reported that the brain does not grow at the same rate with the body in mice models with no microbiome (69). Moreover, it was shown that essential processes of brain such as development, myelination, neurogenesis, and microglial activation are vigorously dependent on gut microbiota combination (70). As explained earlier in previous sections, SARS-COV-2 affects gut microbiota through entering GI system, especially ACE2 receptor in intestine, which consequently causes dysbiosis in the gut (17). ...
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Coronavirus Disease 2019 (COVID-19) is a pandemic disease caused by a new corona virus. COVID-19 affects different people in different ways. COVID-19 could affect the gastrointestinal system via gut microbiota impairment. Gut microbiota could affect lung health through a relationship between gut and lung microbiota, which is named gut-lung axis. Gut microbi-ota impairment plays a role in pathogenesis of various pulmonary disease states, so GI diseases were found to be associated with respiratory diseases. Moreover, most infected people will develop mild to moderate gastrointestinal (GI) symptoms such as diarrhea, vomiting, and stomachache, which is caused by impairment in gut microbiota. Therefore, the current study aimed to review potential role of gut microbiota in patients with COVID-19, its relation with lung axis, Central Nervous System (CNS) axis and improvement with probiotic therapy. Also, this review can be a guide for potential role of gut microbiota in patients with COVID-19.
... Studies from the last decade have demonstrated the importance of the gut commensal bacteria in the regulation of host food metabolism and energy homeostasis, as well as the host immunological response. Notably, the gut microbiome maintains a bidirectional communication with the brain through the microbiome-gut-brain axis, and it is capable of regulating host brain health and behavior (15). While previous studies have largely focused on the bacterial residents (i.e., the bacteriome) of the gut, the fungal microbiome (i.e., the mycobiome) has been less explored. ...
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Huntington's disease (HD) is a neurodegenerative disorder caused by a trinucleotide expansion in the HTT gene, which is expressed throughout the brain and body, including the gut epithelium and enteric nervous system. Afflicted individuals suffer from progressive impairments in motor, psychiatric, and cognitive faculties, as well as peripheral deficits, including the alteration of the gut microbiome. However, studies characterizing the gut microbiome in HD have focused entirely on the bacterial component, while the fungal community (mycobiome) has been overlooked. The gut mycobiome has gained recognition for its role in host homeostasis and maintenance of the gut epithelial barrier. We aimed to characterize the gut mycobiome profile in HD using fecal samples collected from the R6/1 transgenic mouse model (and wild-type littermate controls) from 4 to 12 weeks of age, corresponding to presymptomatic through to early disease stages. Shotgun sequencing was performed on fecal DNA samples, followed by metagenomic analyses. The HD gut mycobiome beta diversity was significantly different from that of wild-type littermates at 12 weeks of age, while no genotype differences were observed at the earlier time points. Similarly, greater alpha diversity was observed in the HD mice by 12 weeks of age. Key taxa, including Malassezia restricta, Yarrowia lipolytica, and Aspergillus species, were identified as having a negative association with HD. Furthermore, integration of the bacterial and fungal data sets at 12 weeks of age identified negative correlations between the HD-associated fungal species and Lactobacillus reuteri. These findings provide new insights into gut microbiome alterations in HD and may help identify novel therapeutic targets.
... The microbial communities encode millions of genes and their associated functions, which work in tandem with human cells to maintain cellular homeostasis (Yatsunenko et al., 2012). A wealth of studies have established the microbiota as an important contributor to essential mammalian functions including metabolism (Trompette et al., 2014), serotonin biosynthesis (Lynch and Pedersen, 2016), neurotransmission (Cryan and O'Mahony, 2011;Surjyadipta and Lukiw Walter, 2013), and immunomodulation (Marcus and Hornef Mathias, 2014;Lloyd Clare and Marsland Benjamin, 2017). The host-microbiota interface is particularly important with evidence suggesting that many chronic inflammatory diseases are associated with significant shifts in the local microbiota towards inflammatory configurations (Hand Timothy et al., 2016). ...
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Background Corynebacterium accolens ( C. accolens ) is a common nasal colonizer, whereas Staphylococcus aureus ( S. aureus ) is typically regarded a pathogenic organism in patients with chronic rhinosinusitis (CRS). This study aims to evaluate the interaction of the two bacteria in vitro . Methods Clinical isolates of C. accolens and S. aureus from sinonasal swabs, as well as primary human nasal epithelial cells (HNECs) cultured from cellular brushings of both healthy and CRS patients were used for this study. The cell-free culture supernatants of all isolates grown alone and in co-cultures were tested for their effects on transepithelial electrical resistance (TER), FITC-Dextran permeability, lactate dehydrogenase (LDH), and IL-6 and IL-8 secretion of HNECs. Confocal scanning laser microscopy and immunofluorescence were also used to visualize the apical junctional complexes. C. accolens cell-free culture supernatants were also tested for antimicrobial activity and growth on planktonic and biofilm S. aureus growth. Results The cell-free culture supernatants of 3\ C. accolens strains (at 60% for S. aureus reference strain and 30% concentration for S. aureus clinical strains) inhibited the growth of both the planktonic S. aureus reference and clinical strains significantly. The C. accolens cell-free culture supernatants caused no change in the TER or FITC-Dextran permeability of the HNEC-ALI cultures, while the cell-free culture supernatants of S. aureus strains had a detrimental effect. Cell-free culture supernatants of C. accolens co-cultured with both the clinical and reference strains of S. aureus delayed the S. aureus -dependent mucosal barrier damage in a dose-dependent manner. Conclusion Corynebacterium accolens cell-free culture supernatants appear to inhibit the growth of the S. aureus planktonic bacteria, and may reduce the mucosal barrier damage caused by S. aureus .
... The gut microbiota can influence the brain and behavior through the blood circulation system, endocrine system, and nervous system, and their mutual influence constitutes the microbe-gut-brain axis (Cryan & O'Mahony, 2011;Foster & McVey Neufeld, 2013). Many studies have shown that changes in the gut microbiota mainly induce ASD directly or indirectly by affecting the immune system pathways, neuroactive pathways, and metabolic pathways Yu & Zhao, 2021). ...
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Objectives Autism spectrum disorder (ASD) is a neurodevelopmental disorder that often occurs in children and seriously affects daily life. In recent years, many studies have shown that intestinal microbial imbalance and intestinal-brain dysfunction may be the critical mechanism for the formation of ASD. This article reviews the changes in the gut microbiota of patients and their impact mechanisms, and the current mechanisms of probiotic and traditional Chinese medicine therapies. Methods A review of contemporary peer-reviewed studies. Pubmed and Cnki were the databases used to identify the studies. Results The majority of the reviewed studies demonstrated that changes in the gut microbiota can directly or indirectly induce ASD by affecting the immune system, nervous system, and endocrine system. Probiotics can improve brain function by affecting the vagus nerve, and improve metabolism by regulating the expression of neuroendocrine hormones. According to the Chinese medicine theory, there are three leading causes of ASD such as deficiency of kidney essence, stagnation of liver qi, and malnutrition of heart spirit. Conclusions The fermentation of Chinese herbal medicine and probiotics can be further studied and may become a new type of treatment for ASD in the future.
... GI dysfunction has been recognized as associated with PD pathogenesis [197]. GM and its metabolites interfere with the host's behavior, immunity, cognition, and metabolism [198][199][200][201]. The changes in the GM composition and its metabolites have been identified as a vital reason for the induction and progression of PD [202]. ...
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Parkinson's disease (PD) is the second-most prevalent neurodegenerative or neuropsychi-atric disease, affecting 1% of seniors worldwide. The gut microbiota (GM) is one of the key access controls for most diseases and disorders. Disturbance in the GM creates an imbalance in the function and circulation of metabolites, resulting in unhealthy conditions. Any dysbiosis could affect the function of the gut, consequently disturbing the equilibrium in the intestine, and provoking pro-inflammatory conditions in the gut lumen, which send signals to the central nervous system (CNS) through the vagus enteric nervous system, possibly disturbing the blood-brain barrier. The neu-roinflammatory conditions in the brain cause accumulation of α-syn, and progressively develop PD. An important aspect of understanding and treating the disease is access to broad knowledge about the influence of dietary supplements on GM. Probiotics are live microorganisms which, when administered in adequate amounts, confer a health benefit on the host. Probiotic supplementation improves the function of the CNS, and improves the motor and non-motor symptoms of PD. Probiotic supplementation could be an adjuvant therapeutic method to manage PD. This review summarizes the role of GM in health, the GM-brain axis, the pathogenesis of PD, the role of GM and diet in PD, and the influence of probiotic supplementation on PD. The study encourages further detailed clinical trials in PD patients with probiotics, which aids in determining the involvement of GM, intestinal mediators, and neurological mediators in the treatment or management of PD.
... In recent years, mounting evidence has suggested that microbially produced neuroactive molecules can modulate the gut-brain axis communication (Cryan and O'Mahony, 2011;Lyte, 2011;Reid, 2011;Cryan and Dinan, 2012). For example, ingestion of a Lactobacillus strain, i.e., L. rhamnosus (JB-1) is able to regulate emotional behaviour and central γ-aminobutyric acid (GABA)ergic system in mouse via vagus nerve pathway (Bravo et al., 2011). ...
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Gut disorders associated to irritable bowel syndrome (IBS) are combined with anxiety and depression. Evidence suggests that microbially produced neuroactive molecules, like γ-aminobutyric acid (GABA), can modulate the gut-brain axis. Two natural strains of Lactococcus lactis and one mutant were characterized in vitro for their GABA production and tested in vivo in rat by oral gavage for their antinociceptive properties. L. lactis NCDO2118 significantly reduced visceral hypersensitivity induced by stress due to its glutamate decarboxylase (GAD) activity. L. lactis NCDO2727 with similar genes for GABA metabolism but no detectable GAD activity had no in vivo effect, as well as the NCDO2118 ΔgadB mutant. The antinociceptive effect observed for the NCDO2118 strain was mediated by the production of GABA in the gastro-intestinal tract and blocked by GABAB receptor antagonist. Only minor changes in the faecal microbiota composition were observed after the L. lactis NCDO2118 treatment. These findings reveal the crucial role of the microbial GAD activity of L. lactis NCDO2118 to deliver GABA into the gastro-intestinal tract for exerting antinociceptive properties in vivo and open avenues for this GRAS (Generally Recognized As safe) bacterium in the management of visceral pain and anxious profile of IBS patients.
... Although the dynamic alterations vary significantly between individuals, a macro equilibrium is a general outcome [25]. While some factors, like autoimmune disease, infection, drugs, illness, and food, may influence the microbiome, beneficial bacteria changes can substantially impact an individual's health [26,27]. ...
Article
One of the most significant illnesses associated with gluten is celiac disease, which encompasses many conditions. It is generally recognized that neurological manifestations can occur either at the time of the disease onset or as the illness continues to develop. One of the main clinical presentations of celiac disease is headache, either in the form of migraine or in an unspecific form. Migraine pathophysiology is intricate and still poorly understood. Several mechanisms involving the gut-brain axis have been proposed to explain this association. These include the interaction of chronic inflammation with inflammatory and vasoactive mediators, the modulation of the intestinal immune environment of the microbiota, and the dysfunction of the autonomic nervous system. However, further research is required to fully comprehend the fundamental mechanisms and pathways at play. This review aims to give a narrative summary of the literature on celiac disease's neurological symptoms, particularly migraines, and to assess any potential associations to dysbiosis, an imbalance in the microbiome.
... It can regulate host immunity, metabolism, neurodevelopment, and behavior (Jasarevic et al., 2017). The gut microbiome modulates central nervous system functioning through the gut-brain axis (Cryan and O'Mahony, 2011;Rhee et al., 2009). This bidirectional axis, involving endocrine, immune, and neural pathways, allows the gut microbiota to impact brain functioning and behaviour, but the extent of these communications is not fully understood yet (Cryan and Dinan, 2012;Gareau et al., 2011). ...
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Adolescence is pivotal for neural and behavioral development across species. During this period, maturation occurs in several biological systems, the most well-recognized being activation of the hypothalamic-pituitary-gonadal axis marking pubertal onset. Increasing comparative studies of sex differences have enriched our understanding of systems integration during neurodevelopment. In recent years, immune signaling has emerged as a key node of interaction between a variety of biological signaling processes. Herein, we review the age- and sex-specific changes that occur in neural, hypothalamic-pituitary, and microbiome systems during adolescence. We then describe how immune signaling interacts with these systems, and review recent preclinical evidence indicating that immune signaling may play a central role in integrating changes in their typical and atypical development during adolescence. Finally, we discuss the translational relevance of these preclinical studies to human health and wellness.
... The intestinal response in IBS mimics one of infection or inflammation and leads to a cascade of inflammatory cells, edema, and release of cytokines [57]. Furthermore, the interplay of a microbiome-gut-brain axis is known to play a role in the disease [58,59]. This constellation of processes illustrates just how hard it may be to model intestinal disease and how our cancer models may very well be missing tissue-defining mechanisms. ...
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The field of cancer research is famous for its incremental steps in improving therapy. The consistent but slow rate of improvement is greatly due to its meticulous use of consistent cancer biology models. However, as we enter an era of increasingly personalized cancer care, including chemo and radiotherapy, our cancer models must be equally able to be applied to all individuals. Patient-derived organoid (PDO) and organ-in-chip (OIC) models based on the micro-physiological bioengineered platform have already been considered key components for preclinical and translational studies. Accounting for patient variability is one of the greatest challenges in the crossover from preclinical development to clinical trials and patient derived organoids may offer a steppingstone between the two. In this review, we highlight how incorporating PDO’s and OIC’s into the development of cancer therapy promises to increase the efficiency of our therapeutics.
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The gut-brain axis describes a bidirectional interplay within the enteric environment between the intestinal epithelium, the mucosal immune system, and the microbiota with the enteric nervous system. This interplay provides a link between exogenous environmental stimuli such as nutrient sensing, and nervous system function, as well as a mechanism of feedback from cortical and sensory centers of the brain to enteric activities. The intestinal epithelium is one of the human body’s largest sources of hormones and neurotransmitters, which have critical effects on neuronal function. The influence of the gut microbiota on these processes appears to be profound; yet to date, it has been insufficiently explored. Disruption of the intestinal microbiota is linked not only to diseases in the gut but also to brain symptomatology, including neurodegenerative and behavioral disorders (Parkinson disease, Alzheimer disease, autism, and anxiety and/or depression). In this review we discuss the cellular wiring of the gut-brain axis, with a particular focus on the epithelial and neuronal interaction, the evidence that has led to our current understanding of the intestinal role in neurologic function, and future directions of research to unravel this important interaction in both health and allergic disease.
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Many studies have shown that stress is associated with gut microbiota. Environmental enrichment (EE) could reduce stress in farm animals; however, limited information is available on the microbial community composition in rabbits raised with or without EE. This study aimed to identify EE influences on the behavior, serum hormonal levels, and cecal microbiota of rabbits. Two hundred Rex rabbits were segregated randomly within four cohorts ( n = 50); reared for 76 d within standardized enclosures (non-enriched) or within cages containing a willow-stick (WS), rubber-duck (RD), or a can of beans (CB). The rabbits’ ingestive, rest, locomotion, exploratory, grooming, and abnormal behavior were observed. The serum hormone levels for rabbits were measured, and cecal specimens were sequencedfrom the V3–V4 region using 16S rRNA amplicons. Environmental enrichment increased feeding and drinking time, promoted exploratory behavior, and reduced abnormal behavior in rabbits. Insulin-like growth factor 1(IGF-1) levels of the enriched cohorts were elevated in comparison to the control cohort. Serum cortisol level for CB cohort was markedly reduced in comparison to the control cohort ( p < 0.05), while dopamine levels for CB cohort peaked. Further, we found that EE mainly affected the dominant microbiota. Several families, such as Erysipelotrichaceae, Tannerellaceae, Enterobacteriaceae, Burkholderiaceae, and Prevotellaceae were markedly reduced within the CB cohort. Bacteria such as Alloprevotella, Bifidobacterium, Enterobacteriaceae, Parabacteroides , and Erysipelatoclostridium were identified as having negative associations with the presence of serum cortisol. EE influenced rabbit behavior and serum hormonal levels, and CB enrichment was the most suitable for rabbits. Further, cecal microbiota composition and diversity were affected by CB enrichment. These findings suggested that CB could be considered for use in rabbit husbandry.
Article
The purpose of the review was to study the effects of stress on the gut microbiota. Results and discussion. The gut microbiota forms a complex microbial community that has a significant impact on human health. The composition of the microbiota varies from person to person, and it changes throughout life. It is known that the microbiome can be altered due to diet, various processes, such as inflammation and/or stress. Like all other areas of medicine, microbiology is constantly growing. The gut microbiota lives in a symbiotic relationship with the human host. It is now believed to interact with almost all human organs, including the central nervous system, in the so-called «gut-brain-microbiome axis». Recently, a growing level of research is showing that microbes play a much bigger role in our lives than previously thought, and can have a myriad of effects on how we behave and think, and even on our mental health. The relationship between the brain and the microbiota is bidirectional and includes endocrine, neuronal, immune, and metabolic pathways. The microbiota interacts with the brain through various mechanisms and mediators, including cytokines, short-chain fatty acids, hormones, and neurotransmitters. According to the hypothalamic-pituitary-adrenocortical axis imbalance theory, hormonal imbalances are closely related to psychiatric illness, anxiety, and stress disorders. Therefore, the gut microbiome is closely related to the development and functioning of this axis. The microbiota can influence neurotransmitter levels in a variety of ways, including the secretion of gamma-aminobutyric acid, norepinephrine, dopamine, and serotonin, and can even regulate serotonin synthesis. These neurotransmitters can influence the hormonal status of the body, and the hormones themselves can influence the formation of the qualitative and quantitative composition of the microbiota. Accordingly, a change in the composition of the intestinal microbiota may be responsible for modifying the hormonal levels of the human body. The endocrine environment in the gut can also be modulated through the neuro-enteroendocrine system. Conclusion. Today, it is known that microbiota changes can be associated with several disorders of the nervous system, such as neuropsychiatric, neurodegenerative and neuroinflammatory processes. Research in recent decades has shown that disorders of the nervous system and mood disorders are associated with changes in the balance of neurotransmitters in the brain. Therefore, understanding the role of microbiota in the development and functioning of the brain is of great importance
Article
Background: As major stress hormones, glucocorticoids (GCs) can directly or indirectly affect the intestinal microflora, although few studies have focused on changes in the composition of the intestinal microflora. In this study, rabbits were randomly divided into two groups, gavage administration with saline, and the same doses of dexamethasone (DEX): 1 mg kg-1 . Seven days later, the microbial diversity of the jejunum contents was analyzed. Results: The gut microflora richness and diversity had no significant difference between the two groups. The proportions of Firmicutes and Bacteroidetes were the most abundant in the jejunum of meat rabbits. DEX-injected led to change the structure of the gut microflora composition and we found that there were six biomarkers with LDA score (Firmicutes, Caproiciproducens, Clostridiales, Clostridia, Psychrobacter, and Psychrobacter_faecalis), moreover, the results of this study provide new insight into alleviating the effects of stress on meat rabbits. Conclusion: It was concluded that glucocorticoids caused changes in the composition of intestinal microflora. This article is protected by copyright. All rights reserved.
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Targeted colonic drug delivery systems are needed for the treatment of endemic colorectal pathologies, such as Crohn's disease, ulcerative colitis, and colorectal cancer. These drug delivery vehicles are difficult to formulate, as they need to remain structurally intact whilst navigating a wide range of physiological conditions across the upper gastrointestinal tract. In this work we show how starch hydrogel bulk structural and molecular level parameters influence their properties as drug delivery platforms. The in vitro protocols mimic in vivo conditions, accounting for physiological concentrations of gastrointestinal hydrolytic enzymes and salts. The structural changes starch gels undergo along the entire length of the human gastrointestinal tract have been quantified, and related to the materials' drug release kinetics for three different drug molecules, and interactions with the large intestinal microbiota. It has been demonstrated how one can modify their choice of starch in order to fine tune its corresponding hydrogel's pharmacokinetic profile.
Chapter
Exclusive breastfeeding is the best way to feed all infants. According to literature, 25 up to 50% of infants develop functional gastrointestinal disorders (FGIDs), and half of them present with a combination of different FGIDs. Although considered as benign transient conditions, FGIDs in infants do have negative short- and long-term health consequences, with a major impact on quality of life of the infant and its family. GI microbiota has been shown to be involved in infantile colic (strong), constipation (moderate), and gastroesophageal reflux (weak evidence). Besides reassurance and anticipatory guidance, nutritional interventions restoring a balanced gastrointestinal microbiota appear to be an effective and safe approach to management in specific scenarios. In those infants that cannot be breastfed, the use of partially hydrolyzed whey proteins, reduced lactose, probiotics, and prebiotics, including human milk oligosaccharides, high levels of magnesium and palm-oil free formulas have been shown to be effective in varying degrees in the prevention and management of specific FGIDs. Dietary interventions can improve the quality of life in FGIDs, particularly in infants. Limited data are available in toddlers. Many toddlers have imbalances in dietary intake, and excess dietary protein may play a role. Recurrent abdominal pain or irritable bowel syndrome is frequent in this age group, with few studies suggesting that interventions with an impact on the gastrointestinal microbiota composition might be beneficial. More data are needed in this age group.
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Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by dopaminergic neuronal loss and α-synuclein (α-syn) aggregation. With the acceleration of population aging process, the incidence of PD is expected to increase, putting a heavy burden on the whole society. Recent studies have found the alterations of gut microbiota (GM) in PD patients and the clinical relevance of these changes, indicating the underlying relationship between GM and PD. Additionally, elevated inflammatory responses originating from the gut play a crucial role in the initiation and progression of PD, which is closely associated with GM. In this review, we will summarize recent studies on the correlation between GM and PD, and discuss the possible pathogenesis of PD mediated by GM and subsequent inflammatory cascades. We will also focus on the promising GM-based therapeutic strategies of PD, including antibiotics, probiotics and/or prebiotics, fecal microbiota transplantation, and dietary interventions, aiming to provide some new therapeutic insights for PD.
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Anorexia nervosa (AN) is characterised by the restriction of energy intake in relation to energy needs and a significantly lowered body weight than normally expected, coupled with an intense fear of gaining weight. Treatment of AN is currently based on psychological and refeeding approaches, but their efficacy remains limited, since 40% of patients after ten years of medical care, still present symptoms of AN. The intestine hosts a large community of microorganisms, called the “microbiota”, which live in symbiosis with the human host. The gut microbiota of a healthy human is dominated by bacteria from two phyla: Firmicutes and majorly Bacteroidetes . However, the proportion in their representation differs on an individual basis and depends on many external factors, such as medical treatment, geographical location, and hereditary, immunological and lifestyle factors. Drastic changes in dietary intake may profoundly impact the composition of the gut microbiota, and the resulting dysbiosis may play a part in the onset and/or maintenance of comorbidities associated with AN, such as gastrointestinal disorders, anxiety, and depression, as well as appetite dysregulation. Furthermore, studies have reported the presence of atypical intestinal microbial composition in patients with AN compared to healthy normal-weight controls. This review addresses the current knowledge about the role of the gut microbiota in the pathogenesis and treatment of AN. The review also focuses on the bidirectional interaction between the gastrointestinal tract and the central nervous system (microbiota-gut-brain axis), considering the potential use of the gut microbiota manipulation in the prevention and treatment of AN.
Article
Motivation Microbiome datasets are often constrained by sequencing limitations. GenBank is the largest collection of publicly available DNA sequences, which is maintained by the National Center of Biotechnology Information (NCBI). The metadata of GenBank records are a largely understudied resource and may be uniquely leveraged to access the sum of prior studies focused on microbiome composition. Here, we developed a computational pipeline to analyze GenBank metadata, containing data on hosts, microorganisms, and their place of origin. This work provides the first opportunity to leverage the totality of GenBank to shed light on compositional data practices that shape how microbiome datasets are formed as well as examine host-microbiome relationships. Results The collected dataset contains multiple kingdoms of microorganisms, consisting of bacteria, viruses, archaea, protozoa, fungi, and invertebrate parasites, and hosts of multiple taxonomical classes, including mammals, birds, and fish. A human data subset of this dataset provides insights to gaps in current microbiome data collection, which is biased towards clinically relevant pathogens. Clustering and phylogenic analysis reveals the potential to use these data to model host taxonomy and evolution, revealing groupings formed by host diet, environment, and coevolution. Availability GenBank Host-Microbiome Pipeline is available at {{https://github.com/bcbi/genbank_holobiome}}. The GenBank loader is available at {{https://github.com/bcbi/genbank_loader}}. Supplementary information Supplementary data are available at Bioinformatics online.
Article
O Transtorno Depressivo Maior (TDM) é um distúrbio psíquico multifatorial, tratado convencionalmente com medicamentos antidepressivos. Os sintomas ocasionados pela própria sintomatologia depressiva e os efeitos colaterais provocados pelos medicamentos são alguns dos fatores que interferem negativamente na adesão dos tratamentos farmacológicos. Atualmente, após os probióticos apresentarem efeitos psicotrópicos, o campo científico tem intensificado esforços para compreender se a suplementação de probióticos serve como tratamento para os transtornos psiquiátricos. Diante disso, o presente estudo formulou o seguinte questionamento: os psicobióticos (probióticos) podem ser denotados como tratamento para o Transtorno Depressivo Maior? Objetivo: responder à questão norteadora através de uma revisão de estudos que suplementaram psicobióticos com a intenção de tratar o Transtorno Depressivo Maior. Metodologia: para esta revisão foi delineado uma busca sistematizada, onde, durante o mês de setembro de 2021, as buscas ocorreram nas bases de dados; Pubmed, Google Scholar, e Scielo, por meio dos descritores “probiotics AND depression AND dysbiosis” em inglês, e em português, e filtragens para a seleção de estudos publicados entre os anos 2005 e 2021. Após a seleção dos materiais, as duplicatas foram gerenciadas no EndNote, e a qualidade metodológica dos estudos randomizados foi avaliada através da ferramenta Risk of Bias-2 (ROB 2). Resultados: houve a predileção de 10 estudos; pré-clínicos (n=4), randomizados (n=5) e piloto aberto (n=1), que cumpriram os critérios de inclusão, e evidenciaram resultados significativos sobre os escores de depressão em escalas psiquiátricas; demonstrando a diminuição da anedonia, reatividade cognitiva, e a insônia de pacientes diagnosticados com o Transtorno Depressivo Maior, além disso, foram observadas mudanças significativas sobre fatores que podem estar associados a patogênese da depressão, como a disbiose, e o estado inflamatório diante a diminuição de biomarcadores inflamatórios. Considerações finais: de acordo com a revisão dos dados, obteve-se a seguinte resposta para a questão norteadora: os psicobióticos podem ser denotados como tratamento para o Transtorno Depressivo Maior. Porém, em razão da necessidade de uma compreensão maior sobre o eixo intestino-cérebro e os mecanismos de ação dos psicobióticos, recomenda-se a suplementação como terapia adjuvante de medicamentos antidepressivos. Sendo assim, estudos com amostras maiores e períodos mais prolongados de intervenção devem ser realizados.
Article
Le trouble dépressif majeur (TDM) est un trouble psychique multifactoriel, traité classiquement par des médicaments antidépresseurs. Les symptômes causés par la symptomatologie dépressive elle-même et les effets secondaires causés par les médicaments sont quelques-uns des facteurs qui interfèrent négativement dans l’adhésion aux traitements pharmacologiques. Actuellement, après que les probiotiques ont montré des effets psychotropes, le domaine scientifique a intensifié ses efforts pour comprendre si la supplémentation en probiotiques sert de traitement pour les troubles psychiatriques. Par conséquent, la présente étude a formulé la question suivante : les psychobiotiques (probiotiques) peuvent-ils être considérés comme un traitement du trouble dépressif majeur ? Objectif : répondre à la question directrice en passant en revue les études qui ont complété les psychobiotiques dans le but de traiter le trouble dépressif majeur. Méthodologie : pour cette revue, une recherche systématique a été conçue, où, au cours du mois de septembre 2021, les recherches ont eu lieu dans les bases de données ; Pubmed, Google Scholar et Scielo, en utilisant les descripteurs « probiotics AND depression AND dysbiosis » en anglais et en portugais, et des filtres pour la sélection des études publiées entre 2005 et 2021. Après sélection des matériaux, les doublons ont été gérés dans EndNote, et le la qualité méthodologique des essais randomisés a été évaluée à l’aide de l’outil Risk of Bias-2 (ROB 2). Résultats : il y avait une préférence pour 10 études ; préclinique (n = 4), randomisée (n = 5) et pilote ouvert (n = 1), qui répondaient aux critères d’inclusion et ont montré des résultats significatifs sur les scores de dépression sur des échelles psychiatriques ; démontrant la diminution de l’anhédonie, de la réactivité cognitive et de l’insomnie chez les patients diagnostiqués avec un trouble dépressif majeur, en outre, des changements significatifs ont été observés sur des facteurs pouvant être associés à la pathogenèse de la dépression, tels que la dysbiose, et l’état inflammatoire face à la diminution des biomarqueurs inflammatoires. Considérations finales : selon l’examen des données, la réponse suivante a été obtenue pour la question directrice : les psychobiotiques peuvent être désignés comme un traitement du trouble dépressif majeur. Cependant, en raison de la nécessité de mieux comprendre l’axe intestin-cerveau et les mécanismes d’action des psychobiotiques, la supplémentation est recommandée comme traitement d’appoint aux antidépresseurs. Par conséquent, des études avec des échantillons plus importants et des périodes d’intervention plus longues doivent être réalisées.
Article
In animal species, the brain-gut axis is a complex bidirectional network between the gastrointestinal (GI) tract and the central nervous system (CNS) consisting of numerous microbial, immune, neuronal, and hormonal pathways that profoundly impact organism development and health. Although nanoplastics (NPs) have been shown to cause intestinal and neural toxicity in fish, the role of the neurotransmitter and intestinal microbiota interactions in the underlying mechanism of toxicity, particularly at environmentally relevant contaminant concentrations, remains unknown. Here, the effect of 44 nm polystyrene nanoplastics (PS-NPs) on the brain-intestine-microbe axis and embryo-larval development in zebrafish (Danio rerio) was investigated. Exposure to 1, 10, and 100 μg/L PS-NPs for 30 days inhibited growth and adversely affected inflammatory responses and intestinal permeability. Targeted metabolomics analysis revealed an alteration of 42 metabolites involved in neurotransmission. The content of 3,4-dihydroxyphenylacetic acid (DOPAC; dopamine metabolite formed by monoamine oxidase activity) was significantly decreased in a dose-dependent manner after PS-NP exposure. Changes in the 14 metabolites correlated with changes to 3 microbial groups, including Proteobacteria, Firmicutes, and Bacteroidetes, as compared to the control group. A significant relationship between Firmicutes and homovanillic acid (0.466, Pearson correlation coefficient) was evident. Eight altered metabolites (l-glutamine (Gln), 5-hydroxyindoleacetic acid (5-HIAA), serotonin, 5-hydroxytryptophan (5-HTP), l-cysteine (Cys), l-glutamic acid (Glu), norepinephrine (NE), and l-tryptophan (l-Trp)) had a negative relationship with Proteobacteria although histamine (His) and acetylcholine chloride (ACh chloride) levels were positively correlated with Proteobacteria. An Associated Network analysis showed that Firmicutes and Bacteroidetes were highly correlated (0.969). Furthermore, PS-NPs accumulated in the gastrointestinal tract of offspring and impaired development of F1 (2 h post-fertilization) embryos, including reduced spontaneous movements, hatching rate, and length. This demonstration of transgenerational deficits is of particular concern. These findings suggest that PS-NPs cause intestinal inflammation, growth inhibition, and restricted development of zebrafish, which are strongly linked to the disrupted regulation within the brain-intestine-microbiota axis. Our study provides insights into how xenobiotics can disrupt the regulation of brain-intestine-microbiota and suggests that these end points should be taken into account when assessing environmental health risks of PS-NPs to aquatic organisms.
Article
Major Depressive Disorder (MDD) is a multifactorial psychic disorder, conventionally treated with antidepressant medications. The symptoms caused by the depressive symptomatology itself and the side effects caused by the medications are some of the factors that negatively interfere in the adherence to pharmacological treatments. Currently, after probiotics have shown psychotropic effects, the scientific field has intensified efforts to understand whether probiotic supplementation serves as a treatment for psychiatric disorders. Therefore, the present study formulated the following question: can psychobiotics (probiotics) be denoted as a treatment for Major Depressive Disorder? Objective: to answer the guiding question through a review of studies that supplemented psychobiotics with the intention of treating Major Depressive Disorder. Methodology: for this review, a systematic search was designed, where, during the month of September 2021, the searches took place in the databases; Pubmed, Google Scholar, and Scielo, using the descriptors “probiotics AND depression AND dysbiosis” in English and Portuguese, and filters for the selection of studies published between 2005 and 2021. After selecting the materials, the duplicates were managed in EndNote, and the methodological quality of randomized trials was assessed using the Risk of Bias-2 (ROB 2) tool. Results: there was a preference for 10 studies; preclinical (n=4), randomized (n=5) and open pilot (n=1), which met the inclusion criteria, and showed significant results on depression scores on psychiatric scales; demonstrating the decrease in anhedonia, cognitive reactivity, and insomnia in patients diagnosed with Major Depressive Disorder, in addition, significant changes were observed on factors that may be associated with the pathogenesis of depression, such as dysbiosis, and the inflammatory state in the face of the decrease of inflammatory biomarkers. Final considerations: according to the data review, the following answer was obtained for the guiding question: psychobiotics can be denoted as a treatment for Major Depressive Disorder. However, due to the need for a better understanding of the gut-brain axis and the mechanisms of action of psychobiotics, supplementation is recommended as an adjunctive therapy to antidepressant drugs. Therefore, studies with larger samples and longer intervention periods should be performed.
Article
Major Depression ist eine multifaktorielle psychische Störung, die konventionell mit Antidepressiva behandelt wird. Die durch die depressive Symptomatik selbst verursachten Symptome und die durch die Medikamente verursachten Nebenwirkungen sind einige der Faktoren, die die Einhaltung pharmakologischer Behandlungen negativ beeinflussen. Nachdem Probiotika psychotrope Wirkungen gezeigt haben, hat der wissenschaftliche Bereich derzeit die Bemühungen intensiviert, um zu verstehen, ob eine probiotische Nahrungsergänzung als Behandlung für psychiatrische Störungen dient. Daher formulierte die vorliegende Studie die folgende Frage: Können Psychobiotika (Probiotika) als Behandlung für Major Depression bezeichnet werden? Ziel: Beantwortung der Leitfrage durch eine Überprüfung von Studien, die Psychobiotika mit der Absicht ergänzen, Major Depression zu behandeln. Methodik: Für diese Überprüfung wurde eine systematische Suche konzipiert, bei der im September 2021 die Suchen in den Datenbanken stattfanden; Pubmed, Google Scholar und Scielo unter Verwendung der Deskriptoren “probiotics AND depression AND dysbiosis” in Englisch und Portugiesisch und Filtern für die Auswahl von Studien, die zwischen 2005 und 2021 veröffentlicht wurden. Nach der Auswahl der Materialien wurden die Duplikate in EndNote verwaltet, und die Die methodische Qualität randomisierter Studien wurde mit dem Werkzeug Risk of Bias-2 (ROB 2) bewertet. Ergebnisse: 10 Studien wurden bevorzugt; präklinisch (n = 4), randomisiert (n = 5) und offener Pilot (n = 1), die die Einschlusskriterien erfüllten und signifikante Ergebnisse bei Depressionswerten auf psychiatrischen Skalen zeigten; die Abnahme der Anhedonie, kognitiven Reaktivität und Schlaflosigkeit bei Patienten mit diagnostizierter Major Depression demonstriert, zusätzlich wurden signifikante Veränderungen bei Faktoren beobachtet, die mit der Pathogenese von Depressionen, wie Dysbiose, und dem Entzündungszustand im Zusammenhang stehen können die Abnahme entzündlicher Biomarker. Abschließende Überlegungen: Nach der Datenrecherche ergab sich folgende Antwort auf die Leitfrage: Psychobiotika können als Behandlung für Major Depression bezeichnet werden. Aufgrund der Notwendigkeit eines besseren Verständnisses der Darm-Hirn-Achse und der Wirkmechanismen von Psychobiotika wird jedoch eine Supplementierung als Begleittherapie zu Antidepressiva empfohlen. Daher sollten Studien mit größeren Stichproben und längeren Interventionszeiträumen durchgeführt werden.
Article
Il Disturbo Depressivo Maggiore (DDM) è un disturbo psichico multifattoriale, convenzionalmente trattato con farmaci antidepressivi. I sintomi causati dalla stessa sintomatologia depressiva e gli effetti collaterali causati dai farmaci sono alcuni dei fattori che interferiscono negativamente nell’aderenza ai trattamenti farmacologici. Attualmente, dopo che i probiotici hanno mostrato effetti psicotropi, il campo scientifico ha intensificato gli sforzi per capire se l’integrazione di probiotici serve come trattamento per i disturbi psichiatrici. Pertanto, il presente studio ha formulato la seguente domanda: gli psicobiotici (probiotici) possono essere indicati come trattamento per il Disturbo Depressivo Maggiore? Obiettivo: rispondere alla domanda guida attraverso una rassegna di studi che integravano la psicobiotica con l’intento di trattare il Disturbo Depressivo Maggiore. Metodologia: per questa revisione è stata progettata una ricerca sistematica, dove, nel mese di settembre 2021, sono state effettuate le ricerche nelle banche dati; Pubmed, Google Scholar e Scielo, utilizzando i descrittori “probiotics AND depression AND dysbiosis” in inglese e portoghese, e filtri per la selezione degli studi pubblicati tra il 2005 e il 2021. Dopo aver selezionato i materiali, i duplicati sono stati gestiti in EndNote e il la qualità metodologica degli studi randomizzati è stata valutata utilizzando lo strumento Risk of Bias-2 (ROB 2). Risultati: c’è stata una preferenza per 10 studi; preclinico (n=4), randomizzato (n=5) e pilota aperto (n=1), che soddisfacevano i criteri di inclusione e mostravano risultati significativi sui punteggi della depressione su scale psichiatriche; dimostrando la diminuzione di anedonia, reattività cognitiva e insonnia nei pazienti con diagnosi di Disturbo Depressivo Maggiore, inoltre, sono stati osservati cambiamenti significativi su fattori che possono essere associati alla patogenesi della depressione, come la disbiosi, e lo stato infiammatorio a fronte di la diminuzione dei biomarcatori infiammatori. Considerazioni finali: secondo la revisione dei dati, alla domanda guida è stata ottenuta la seguente risposta: gli psicobiotici possono essere indicati come trattamento per il Disturbo Depressivo Maggiore. Tuttavia, a causa della necessità di una migliore comprensione dell’asse intestino-cervello e dei meccanismi d’azione degli psicobiotici, l’integrazione è raccomandata come terapia aggiuntiva ai farmaci antidepressivi. Pertanto, dovrebbero essere eseguiti studi con campioni più grandi e periodi di intervento più lunghi.
Article
Большое депрессивное расстройство (БДР) — это многофакторное психическое расстройство, обычно лечится антидепрессантами. Симптомы, вызванные самой депрессивной симптоматикой, и побочные эффекты, вызванные лекарствами, являются одними из факторов, отрицательно влияющих на приверженность к фармакологическому лечению. В настоящее время, после того как пробиотики продемонстрировали психотропные эффекты, научная сфера активизировала усилия, чтобы понять, служат ли пробиотические добавки средством лечения психических расстройств. Таким образом, в настоящем исследовании сформулирован следующий вопрос: можно ли считать психобиотики (пробиотики) средством лечения Большое депрессивное расстройство ? Цель: ответить на главный вопрос посредством обзора исследований, в которых психобиотики добавлялись с целью лечения Большое депрессивное расстройство . Методология: для этого обзора был разработан систематический поиск, где в течение сентября 2021 года поиски проводились в базах данных; Pubmed, Google Scholar и Scielo с использованием дескрипторов «probiotics AND depression AND dysbiosis» на английском и португальском языках и фильтров для отбора исследований, опубликованных в период с 2005 по 2021 год. После выбора материалов дубликаты были обработаны в EndNote, а Методологическое качество рандомизированных исследований оценивали с помощью инструмента Risk of Bias-2 (ROB 2). Результаты: предпочтение было отдано 10 исследованиям; доклинический (n=4), рандомизированный (n=5) и открытый пилотный (n=1), которые соответствовали критериям включения и показали значимые результаты по шкале депрессии по психиатрическим шкалам; продемонстрировав снижение ангедонии, когнитивной реактивности и бессонницы у больных с диагнозом Большое депрессивное расстройство, кроме того, отмечены существенные изменения факторов, которые могут быть связаны с патогенезом депрессии, таких как дисбиоз, воспалительное состояние на фоне снижение воспалительных биомаркеров. Заключительные соображения: по результатам обзора данных получен следующий ответ на наводящий вопрос: психобиотики можно обозначить как средство для лечения Большое депрессивное расстройство. Однако из-за необходимости лучшего понимания оси кишечник-мозг и механизмов действия психобиотиков добавки рекомендуются в качестве дополнительной терапии к антидепрессантам. Поэтому следует проводить исследования с более крупными выборками и более длительными периодами вмешательства.
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Background: Numerous studies have shown that exposure to prenatal maternal stress (PMS) is associated with various psychopathological outcomes of offspring. The accumulating evidence linking bacteria in the gut and neurons in the brain (the microbiota-gut-brain axis) has been aconsensus; however, there is a lack of research on the involvement mechanism of gut microbiota in the regulation of the BDNF/CREB signaling pathway in the hippocampus of prenatally stressed offspring. Methods: Pregnant rats were subjected to chronic unpredictable mild stress (CUMS) to establish the prenatal maternal stress model. The body weight was measured and the behavioral changes were recorded. Offspring were tested to determine emotional state using sucrose preference test (SPT), open-field test (OFT) and suspended tail test (STT). Gut microbiota was evaluated by sequencing the microbial 16S rRNA V3-V4 region, and the interactive analysis of bacterial community structure and diversity was carried out. The expression of hippocampal BDNF, TrkB and CREB mRNA and proteins were respectively measured using RT-PCR and Western blotting. Results: Prenatal maternal stress increased maternal plasma corticosterone levels, slowed maternal weight gain and caused depression-like behaviors (all P < 0.05). In offspring, prenatal maternal stress increased plasma corticosterone levels (P < 0.05) and emotional behavior changes (depression-like state) were observed (P < 0.05). The species abundance, diversity and composition of the offspring's gut microbiota changed after the maternal stress during pregnancy (P < 0.05). Compared with the control group's offspring, the species abundance of Lactobacillaceae was dropped, while the abundance of the Muribaculaceae species abundance was risen. Concurrent, changes in the hippocampal structure of the offspring and decreases in expression of BDNF/CREB signaling were noted (P < 0.05). Conclusions: Prenatal maternal stress leads to high corticosterone status and abnormal emotion behavior of offspring, which may be associated with the abnormal BDNF/CREB signaling in hippocampus of offspring caused by the change of gut microbiota composition.
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An optimally operating microbiome supports protective, metabolic, and immune functions, but disruptions produce metabolites and toxins which can be involved in many conditions. Probiotics have the potential to manage these. However, their use in vulnerable people is linked to possible safety concerns and maintaining their viability is difficult. Interest in postbiotics is therefore increasing. Postbiotics contain inactivated microbial cells or cell components, thus are more stable and exert similar health benefits to probiotics. To review the evidence for the clinical benefits of postbiotics in highly prevalent conditions and consider future potential areas of benefit. There is growing evidence revealing the diverse clinical benefits of postbiotics in many prevalent conditions. Postbiotics could offer a novel therapeutic approach and may be a safer alternative to probiotics. Establishing interaction mechanisms between postbiotics and commensal microorganisms will improve the understanding of potential clinical benefits and may lead to targeted postbiotic therapy.
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In a previous clinical study, a probiotic formulation (PF) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (PF) decreased stress-induced gastrointestinal discomfort. Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychological distress. The aim of the present study was to investigate the anxiolytic-like activity of PF in rats, and its possible effects on anxiety, depression, stress and coping strategies in healthy human volunteers. In the preclinical study, rats were daily administered PF for 2 weeks and subsequently tested in the conditioned defensive burying test, a screening model for anti-anxiety agents. In the clinical trial, volunteers participated in a double-blind, placebo-controlled, randomised parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist (HSCL-90), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale, the Coping Checklist (CCL) and 24 h urinary free cortisol (UFC). Daily subchronic administration of PF significantly reduced anxiety-like behaviour in rats (P < 0·05) and alleviated psychological distress in volunteers, as measured particularly by the HSCL-90 scale (global severity index, P < 0·05; somatisation, P < 0·05; depression, P < 0·05; and anger-hostility, P < 0·05), the HADS (HADS global score, P < 0·05; and HADS-anxiety, P < 0·06), and by the CCL (problem solving, P < 0·05) and the UFC level (P < 0·05). L. helveticus R0052 and B. longum R0175 taken in combination display anxiolytic-like activity in rats and beneficial psychological effects in healthy human volunteers.
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The brain-gut axis is a key regulator of normal intestinal physiology; for example, psychological stress is linked to altered gut barrier function, development of food allergies and changes in behaviour. Whether intestinal events, such as enteric bacterial infections and bacterial colonisation, exert a reciprocal effect on stress-associated behaviour is not well established. To determine the effects of either acute enteric infection or absence of gut microbiota on behaviour, including anxiety and non-spatial memory formation. Behaviour was assessed following infection with the non-invasive enteric pathogen, Citrobacter rodentium in both C57BL/6 mice and germ-free Swiss-Webster mice, in the presence or absence of acute water avoidance stress. Whether daily treatment with probiotics normalised behaviour was assessed, and potential mechanisms of action evaluated. No behavioural abnormalities were observed, either at the height of infection (10 days) or following bacterial clearance (30 days), in C rodentium-infected C57BL/6 mice. When infected mice were exposed to acute stress, however, memory dysfunction was apparent after infection (10 days and 30 days). Memory dysfunction was prevented by daily treatment of infected mice with probiotics. Memory was impaired in germ-free mice, with or without exposure to stress, in contrast to conventionally reared, control Swiss-Webster mice with an intact intestinal microbiota. The intestinal microbiota influences the ability to form memory. Memory dysfunction occurs in infected mice exposed to acute stress, while in the germ-free setting memory is altered at baseline.
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Recent evidence postulates a role of hippocampal neurogenesis in anxiety behavior. Here we report that elevated levels of neurogenesis elicit increased anxiety in rodents. Mice performing voluntary wheel running displayed both highly elevated levels of neurogenesis and increased anxiety in three different anxiety-like paradigms: the open field, elevated O-maze, and dark-light box. Reducing neurogenesis by focalized irradiation of the hippocampus abolished this exercise-induced increase of anxiety, suggesting a direct implication of hippocampal neurogenesis in this phenotype. On the other hand, irradiated mice explored less frequently the lit compartment of the dark-light box test irrespective of wheel running, suggesting that irradiation per se induced anxiety as well. Thus, our data suggest that intermediate levels of neurogenesis are related to the lowest levels of anxiety. Moreover, using c-Fos immunocytochemistry as cellular activity marker, we observed significantly different induction patterns between runners and sedentary controls when exposed to a strong anxiogenic stimulus. Again, this effect was altered by irradiation. In contrast, the well-known induction of brain-derived neurotrophic factor (BDNF) by voluntary exercise was not disrupted by focal irradiation, indicating that hippocampal BDNF levels were not correlated with anxiety under our experimental conditions. In summary, our data demonstrate to our knowledge for the first time that increased neurogenesis has a causative implication in the induction of anxiety.
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The use of probiotics is increasing in popularity for both the prevention and treatment of a variety of diseases. While a growing number of well-conducted, prospective, randomized, controlled, clinical trials are emerging and investigations of underlying mechanisms of action are being undertaken, questions remain with respect to the specific immune and physiological effects of probiotics in health and disease. This Review considers recent advances in clinical trials of probiotics for intestinal disorders in both adult and pediatric populations. An overview of recent in vitro and in vivo research related to potential mechanisms of action of various probiotic formulations is also considered.
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Enquiries among patients on the one hand and experimental and observational studies on the other suggest an influence of stress on inflammatory bowel diseases (IBD). However, since this influence remains hypothetical, further research is essential. We aimed to devise recommendations for future investigations in IBD by means of scrutinizing previously applied methodology. We critically reviewed prospective clinical studies on the effect of psychological stress on IBD. Eligible studies were searched by means of the PubMed electronic library and through checking the bibliographies of located sources. We identified 20 publications resulting from 18 different studies. Sample sizes ranged between 10 and 155 participants. Study designs in terms of patient assessment, control variables, and applied psychometric instruments varied substantially across studies. Methodological strengths and weaknesses were irregularly dispersed. Thirteen studies reported significant relationships between stress and adverse outcomes. Study designs, including accuracy of outcome assessment and repeated sampling of outcomes (i.e. symptoms, clinical, and endoscopic), depended upon conditions like sample size, participants' compliance, and available resources. Meeting additional criteria of sound methodology, like taking into account covariates of the disease and its course, is strongly recommended to possibly improve study designs in future IBD research.
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While bidirectional brain-gut interactions are well known mechanisms for the regulation of gut function in both healthy and diseased states, a role of the enteric flora--including both commensal and pathogenic organisms--in these interactions has only been recognized in the past few years. The brain can influence commensal organisms (enteric microbiota) indirectly, via changes in gastrointestinal motility and secretion, and intestinal permeability, or directly, via signaling molecules released into the gut lumen from cells in the lamina propria (enterochromaffin cells, neurons, immune cells). Communication from enteric microbiota to the host can occur via multiple mechanisms, including epithelial-cell, receptor-mediated signaling and, when intestinal permeability is increased, through direct stimulation of host cells in the lamina propria. Enterochromaffin cells are important bidirectional transducers that regulate communication between the gut lumen and the nervous system. Vagal, afferent innervation of enterochromaffin cells provides a direct pathway for enterochromaffin-cell signaling to neuronal circuits, which may have an important role in pain and immune-response modulation, control of background emotions and other homeostatic functions. Disruption of the bidirectional interactions between the enteric microbiota and the nervous system may be involved in the pathophysiology of acute and chronic gastrointestinal disease states, including functional and inflammatory bowel disorders.
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Chronic fatigue syndrome (CFS) is complex illness of unknown etiology. Among the broad range of symptoms, many patients report disturbances in the emotional realm, the most frequent of which is anxiety. Research shows that patients with CFS and other so-called functional somatic disorders have alterations in the intestinal microbial flora. Emerging studies have suggested that pathogenic and non-pathogenic gut bacteria might influence mood-related symptoms and even behavior in animals and humans. In this pilot study, 39 CFS patients were randomized to receive either 24 billion colony forming units of Lactobacillus casei strain Shirota (LcS) or a placebo daily for two months. Patients provided stool samples and completed the Beck Depression and Beck Anxiety Inventories before and after the intervention. We found a significant rise in both Lactobacillus and Bifidobacteria in those taking the LcS, and there was also a significant decrease in anxiety symptoms among those taking the probiotic vs controls (p = 0.01). These results lend further support to the presence of a gut-brain interface, one that may be mediated by microbes that reside or pass through the intestinal tract.
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New neurons in the adult dentate gyrus are widely held to incorporate into hippocampal circuitry via a stereotypical sequence of morphological and physiological transitions, yet the molecular control over this process remains unclear. We studied the role of brain-derived neurotrophic factor (BDNF)/TrkB signaling in adult neurogenesis by deleting the full-length TrkB via Cre expression within adult progenitors in TrkBlox/lox mice. By 4 weeks after deletion, the growth of dendrites and spines is reduced in adult-born neurons demonstrating that TrkB is required to create the basic organization of synaptic connections. Later, when new neurons normally display facilitated synaptic plasticity and become preferentially recruited into functional networks, lack of TrkB results in impaired neurogenesis-dependent long-term potentiation and cell survival becomes compromised. Because of the specific lack of TrkB signaling in recently generated neurons a remarkably increased anxiety-like behavior was observed in mice carrying the mutation, emphasizing the contribution of adult neurogenesis in regulating mood-related behavior. • BDNF • LTP • neurogenesis • plasticity • dendritogenesis
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Experiments were performed using physiological measures and behavioural parameters to find the acclimatization period in mice to common scientific procedures. Corticosterone levels were significantly elevated in mice killed immediately after being moved to an experimental room (P < 0.05) but levels returned to the normal in less than 1 day, despite mice being exposed to additional stressors such as novel environment, new cages, new bedding material, separation from their cage mates, regrouping, isolation in individually housed mice and a new handler. Behaviours such as rearing, climbing, grooming, feeding and sexual, changed significantly immediately after transportation of mice but most of these behaviours stabilized relatively quickly. In spite of the corticosterone levels, our behavioural observations suggest that even 4 days were not enough to allow the mice to acclimatize fully.
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AIM: To determine whether Salmonella Typhimurium (STM) in gastrointestinal tract can induce the functional activation of brain, whether the vagus nerve involves in signaling immune information from gastrointestinal tract to brain and how it influences the immune function under natural infection condition. METHODS: Animal model of gastrointestinal tract infection in the rat was established by an intubation of Salmonella Typhimurium (STM) into stomach to mimic the condition of natural bacteria infection. Subdiagphragmatic vagotomy was performed in some of the animals 28 days before infection. The changes of Fos expression visualized with immunohistochemistry technique in hypothalamic paraventricular nucleus (PVN) and superaoptic nucleus (SON) were counted. Meanwhile, the percentage and the Mean Intensities of Fluorescent (MIFs) of CD4+ and CD8+ T cells in peripheral blood were measured by using flow cytometry (FCM), and the pathological changes in ileum and mesenteric lymph node were observed in HE stained sections. RESULTS: In bacteria-stimulated groups, inflammatory pathological changes were seen in ileum and mesenteric lymph node. The percentages of CD4+ T cells in peripheral blood were decreased from 42% ± 4.5% to 34% ± 4.9% (P < 0.05) and MIFs of CD8+ T cells were also decreased from 2.9 ± 0.39 to 2.1 ± 0.36 (P < 0.05) with STM stimulation. All of them proved that our STM-infection model was reliable. Fos immunoreactive (Fos-ir) cells in PVN and SON increased significantly with STM stimulation, from 189 ± 41 to 467 ± 62 (P < 0.05) and from 64 ± 21 to 282 ± 47 (P < 0.05) individually, which suggested that STM in gastrointestinal tract induced the functional activation of brain. Subdiagphragmatic vagotomy attenuated Fos expression in PVN and SON induced by STM, from 467 ± 62 to 226 ± 45 (P < 0.05) and from 282 ± 47 to 71 ± 19 (P < 0.05) individually, and restored the decreased percentages of CD4+ T cells induced by STM from 34% ± 4.9% to original level 44% ± 6.0% (P < 0.05). In addition, subdiagphragmatic vagotomy itself also decreased the percentages of CD8+ T cells (from 28% ± 3.0% to 21% ± 5.9%, P < 0.05) and MIFs of CD4+ (from 6.6 ± 0.6 to 4.9 ± 1.0, P < 0.05) and CD8+ T cells (from 2.9 ± 0.39 to1.4 ± 0.34, P < 0.05). Both of them manifested the important role of vagus nerve in transmitting immune information from gut to brain and maintaining the immune balance of the organism. CONCLUSION: Vagus nerve does involve in transmitting abdominal immune information into the brain in STM infection condition and play an important role in maintenance of the immune balance of the organism.
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An increase in inflammatory response and an imbalance between T-helper (Th) 1 and 2 functions have been implicated in major depression. The aims of the present study were to 1) study the relationship between pro- and anti-inflammatory cytokines and between Th1 and Th2 produced cytokines in depressed patients and 2) evaluate and compare the effect of treatments with electroacupuncture (EA) and fluoxetine on these cytokines. 95 outpatients with major depressive disorder were treated for 6 weeks with EA, fluoxetine or placebo. Hamilton Depression Rating Scale (HDRS) and Clinical Global Impression (CGI) were used to assess severity and therapeutic effects. 30 volunteers served as controls. Serum cytokine concentrations were measured by ELISA. Increased proinflammatory cytokine interleukin (IL)-1beta and decreased anti-inflammatory cytokine IL-10 were found in the depressed patients. By contract, Th1 produced proinflammatory cytokines, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma were decreased, and Th2 produced cytokine IL-4 was significantly increased in depressed patients. The ratio of IFN/IL-4 was also increased. Both acupuncture and fluoxetine treatments, but not the placebo, reduced IL-1beta concentrations in responders. However, only acupuncture attenuated TNF-alpha concentration and INF-gamma/IL-4 ratio towards the control level. These results suggest that an imbalance between the pro- and anti-inflammatory cytokines (IL-1 and IL-10), and between Th1 and Th2 cytokines (INF-gamma or TNF-alpha and IL-4) occurred in untreated depressed patients. Both EA and fluoxetine had an anti-inflammatory effect by reducing IL-1beta. EA treatment also restored the balance between Th1 and Th2 systems by increasing TNF-alpha and decreasing IL-4.
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Although many people are aware of the communication that occurs between the gastrointestinal (GI) tract and the central nervous system, fewer know about the ability of the central nervous system to influence the microbiota or of the microbiota's influence on the brain and behavior. Within the GI tract, the microbiota have a mutually beneficial relationship with their host that maintains normal mucosal immune function, epithelial barrier integrity, motility, and nutrient absorption. Disruption of this relationship alters GI function and disease susceptibility. Animal studies suggest that perturbations of behavior, such as stress, can change the composition of the microbiota; these changes are associated with increased vulnerability to inflammatory stimuli in the GI tract. The mechanisms that underlie these alterations are likely to involve stress-induced changes in GI physiology that alter the habitat of enteric bacteria. Furthermore, experimental perturbation of the microbiota can alter behavior, and the behavior of germ-free mice differs from that of colonized mice. Gaining a better understanding of the relationship between behavior and the microbiota could provide insight into the pathogenesis of functional and inflammatory bowel disorders.
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Antidepressant drugs have been suggested to regulate synaptic transmission and structure. We hypothesised that antidepressant-induced changes in synapses and their associated proteins might become more apparent if they were measured under conditions of reduced synapse density. Therefore, in the present study, we examined whether chronic treatment with the antidepressant, fluoxetine alters expression of synaptic proteins in the hippocampus of rodents that underwent ovariectomy, a procedure which reportedly decreases synapse density in the CA1 region of the rat hippocampus. Using Western blotting, we measured changes in hippocampal expression of proteins associated with synapse structure, strength and activity namely, postsynaptic density protein 95 (PSD-95), the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R) subunit GluR1 and phosphosynapsin (Ser9), respectively. We found that fluoxetine treatment increased expression of phosphosynapsin, PSD-95 and synaptic GluR1 (but not total GluR1) in the hippocampus of ovariectomized but not sham rats.
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Adverse early life events are associated with a maladaptive stress response system and might increase the vulnerability to disease in later life. Several disorders have been associated with early life stress, ranging from depression to irritable bowel syndrome. This makes the identification of the neurobiological substrates that are affected by adverse experiences in early life invaluable. The purpose of this study was to assess the effect of early life stress on the brain-gut axis. Male rat pups were stressed by separating them from their mothers for 3 hours daily between postnatal days 2-12. The control group was left undisturbed with their mothers. Behavior, immune response, stress sensitivity, visceral sensation, and fecal microbiota were analyzed. The early life stress increased the number of fecal boli in response to a novel stress. Plasma corticosterone was increased in the maternally separated animals. An increase in the systemic immune response was noted in the stressed animals after an in vitro lipopolysaccharide challenge. Increased visceral sensation was seen in the stressed group. There was an alteration of the fecal microbiota when compared with the control group. These results show that this form of early life stress results in an altered brain-gut axis and is therefore an important model for investigating potential mechanistic insights into stress-related disorders including depression and IBS.