Article
To read the full-text of this research, you can request a copy directly from the authors.

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.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... 99 When PET and functional magnetic resonance imaging (fMRI) are used to evaluate the response of the ACC to rectal distention or to the anticipation of distension, patients with IBS display preferential activation of the MCC and less activation of the pACC than controls. 97,100,101 In IBS, activation of the descending inhibitory pain pathway that originates in the opioid-rich pACC might be supplanted by activation of the MCC, the area associated with fear and unpleasantness. Similar fi ndings occur in patients with somatization 102 and post-traumatic stress disorder (PTSD). ...
... These changes, along with an altered immune response, can result in inflammation and susceptibility to both IBS (particularly postinfection IBS) and IBD. 100 Conversely, alteration of the intestinal microflora can reciprocate back via the braingut axis to affect CNS functioning, including mood, learning, and memory. 101 A useful model highlighting the reciprocal relationship between stress and altered immunity is the condition known as postinfection IBS, which develops in about 10% of patients after a bout of infectious enteritis. ...
... 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]. ...
... 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]. ...
Article
Full-text available
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.
... reuteri-treated relative to HK-treated female, but not male voles, along with the sex-specific effects seen in neurochemical marker expression and microbiome composition (see below) is intriguing, as sex-specific neurochemical regulation of social behaviors have been reported in prairie voles (DeVries et al., 1995;Cho et al., 1999) as well as in rats and mice Kopec et al., 2018;Rigney et al., 2020). Although L. reuteri treatment has also been shown to alter stress-related behaviors in other species (Cryan and O'Mahony, 2011;Marin et al., 2017), we found no effects of L. reuteri on anxiety-like behavior in the present study. These data further indicate that L. reuteri can affect behaviors in a species-and behavior-specific manner. ...
Article
Full-text available
Research on the role of gut microbiota in behavior has grown dramatically. The probiotic L. reuteri can alter social and stress-related behaviors – yet, the underlying mechanisms remain largely unknown. Although traditional laboratory rodents provide a foundation for examining the role of L. reuteri on the gut-brain axis, they do not naturally display a wide variety of social behaviors. Using the highly-social, monogamous prairie vole (Microtus ochrogaster), we examined the effects of L. reuteri administration on behaviors, neurochemical marker expression, and gut-microbiome composition. Females, but not males, treated with live L. reuteri displayed lower levels of social affiliation compared to those treated with heat-killed L. reuteri. Overall, females displayed a lower level of anxiety-like behaviors than males. Live L. reuteri-treated females had lower expression of corticotrophin releasing factor (CRF) and CRF type-2-receptor in the nucleus accumbens, and lower vasopressin 1a-receptor in the paraventricular nucleus of the hypothalamus (PVN), but increased CRF in the PVN. There were both baseline sex differences and sex-by-treatment differences in gut microbiome composition. Live L. reuteri increased the abundance of several taxa, including Enterobacteriaceae, Lachnospiraceae NK4A136, and Treponema. Interestingly, heat-killed L. reuteri increased abundance of the beneficial taxa Bifidobacteriaceae and Blautia. There were significant correlations between changes in microbiota, brain neurochemical markers, and behaviors. Our data indicate that L. reuteri impacts gut microbiota, gut-brain axis and behaviors in a sex-specific manner in socially-monogamous prairie voles. This demonstrates the utility of the prairie vole model for further examining causal impacts of microbiome on brain and behavior.
... Urolithin A thus has properties that would also be beneficial in the treatment of IVDD and LBP. The gut microbiome-IVD axis proposed by Li et al.348 and Rajasekaran et al.349 may serve as an intrinsic delivery system that could be utilized to deliver efficacious gut metabolites such as urolithin A to the IVD in a similar manner to how bioactive gut metabolites are transported by the gut brain axis.[350][351][352] This also gives some credibility to the consumption of diets enriched in probiotic compounds as a potential therapeutic option to promote tissue repair.This proposal warrants further investigation.Cannabidiol (CBD) displays potential in the management of neuropathic LBP. ...
Article
Full-text available
Animal models have been invaluable in the identification of molecular events occurring in and contributing to intervertebral disc (IVD) degeneration and important therapeutic targets have been identified. Some outstanding animal models (murine, ovine, chondrodystrophoid canine) have been identified with their own strengths and weaknesses. The llama/alpaca, horse and kangaroo have emerged as new large species for IVD studies, and only time will tell if they will surpass the utility of existing models. The complexity of IVD degeneration poses difficulties in the selection of the most appropriate molecular target of many potential candidates, to focus on in the formulation of strategies to effect disc repair and regeneration. It may well be that many therapeutic objectives should be targeted simultaneously to effect a favorable outcome in human IVD degeneration. Use of animal models in isolation will not allow resolution of this complex issue and a paradigm shift and adoption of new methodologies is required to provide the next step forward in the determination of an effective repairative strategy for the IVD. AI has improved the accuracy and assessment of spinal imaging supporting clinical diagnostics and research efforts to better understand IVD degeneration and its treatment. Implementation of AI in the evaluation of histology data has improved the usefulness of a popular murine IVD model and could also be used in an ovine histopathological grading scheme that has been used to quantify degenerative IVD changes and stem cell mediated regeneration. These models are also attractive candidates for the evaluation of novel anti‐oxidant compounds that counter inflammatory conditions in degenerate IVDs and promote IVD regeneration. Some of these compounds also have pain‐relieving properties. AI has facilitated development of facial recognition pain assessment in animal IVD models offering the possibility of correlating the potential pain alleviating properties of some of these compounds with IVD regeneration. Animal models of IVD deneration have yielded invaluable information on the pathobiology of this degenerative condition and identified prospective therapeutic targets.The complexity of the degenerative changes and multiple therapeutic targets identified by these models suggests artificial intelligence methodology may be required to unravel these complexities and provide a rationale way forward in the development of effective repair strategies.
... In addition to coordinating and integrating gastrointestinal functions, it also connects the brain and peripheral functions [12]. Many reactions occur in these processes, such as the activation of immune responses, the protection of intestinal permeability, and the transmission of gastrointestinal-endocrine signals [13]. The gut microbiota is currently recognized as a key regulator of a smooth two-way dialogue between the gut and the brain (gut-brain axis). ...
Article
Full-text available
With the increase in human mean age, the prevalence of neurodegenerative diseases (NDs) also rises. This negatively affects mental and physiological health. In recent years, evidence has revealed that anthocyanins could regulate the functioning of the central nervous system (CNS) through the microbiome-gut-brain axis, which provides a new perspective for treating NDs. In this review, the protective effects and mechanisms of anthocyanins against NDs are summarized, especially the interaction between anthocyanins and the intestinal microbiota, and the microbial-intestinal-brain axis system is comprehensively discussed. Moreover, anthocyanins achieve the therapeutic purpose of NDs by regulating intestinal microflora and certain metabolites (protocateic acid, vanillic acid, etc.). In particular, the inhibitory effect of tryptophan metabolism on some neurotransmitters and the induction of blood-brain barrier permeability by butyrate production has a preventive effect on NDs. Overall, it is suggested that microbial-intestinal-brain axis may be a novel mechanism for the protective effect of anthocyanins against NDs.
... The second hit can include secondary immune challenge [41], different kind of stress [30,44,45] or gut dysbiosis induced by antibiotics [11,46]. Antimicrobial treatment can be applied to induce microbiome perturbation under controlled conditions and can therefore be used in animals as a methodological tool to evaluate the effects of the gut microbiota on behavior [14,47]. In mice and rats, antibiotic administration in early life [48][49][50], adolescence [51] and adulthood [52][53][54] has been well studied and shown to alter many factors, including hormone levels, gene expression, anxiety-related responses, exploratory and social behaviors, and cognitive functions. ...
Preprint
Full-text available
The present study investigated whether neonatal exposure to the proinflammatory endotoxin lipopolysaccharide (LPS) followed by antibiotic (ATB)-induced dysbiosis in early adulthood could induce schizophrenia-like behavioral changes in adult male rats. The combination of these two stressors resulted in decreased weight gain, but no significant behavioral abnormalities were observed. LPS treatment resulted in adult rats hypoactivity and induced anxiety-like behavior in the social recognition paradigm, but these behavioral changes were not exacerbated by ATB-induced gut dysbiosis. ATB treatment seriously disrupted the gut bacterial community, but dysbiosis did not affect locomotor activity, social recognition, and acoustic reactivity in adult rats. Fecal bacterial community analyzes showed no differences between the LPS challenge exposed/unexposed rats, while the effect of ATB administration was decisive regardless of prior LPS exposure. ATB treatment resulted in significantly decreased bacterial diversity, suppression of Clostridiales and Bacteroidales, and increases in Lactobacillales, Enterobacteriales, and Burkholderiales. The persistent effect of LPS on some aspects of behavior suggests a long-term effect of early toxin exposure that was not observed in ATB-treated animals. However, an anti-inflammatory protective effect of ATB cannot be assumed because of the increased abundance of pro-inflammatory, potentially pathogenic bacteria (Proteus, Suttrella) and the elimination of the bacterial families Ruminococcaceae and Lachnospiraceae, which are generally considered beneficial for gut health.
... Some of its other beneficial functions include digestion of plant polysaccharides and host glycans in the colon, production of essential vitamins, functional and structural maturation of the GIT and development of the intestinal surface area and microvasculature [18]. Moreover, a healthy gut microbiota influences the gut-brain axis and shapes stress related symptoms such as anxiety and pain [19] and is also implicated in appetite control [20]. ...
Article
Background: The importance of gut microbiota in human health is being increasingly studied. Imbalances in gut microbiota have been associated with infection, inflammation, and obesity. Antibiotic use is the most common and significant cause of major alterations in the composition and function of the gut microbiota and can result in colonization with multidrug-resistant bacteria. Methods: The purpose of this review is to present existing evidence on how microbiota modulation and prevention of gut dysbiosis can serve as tools to combat antimicrobial resistance. Results: While the spread of antibiotic-resistant pathogens requires antibiotics with novel mechanisms of action, the number of newly discovered antimicrobial classes remains very low. For this reason, the application of alternative modalities to combat antimicrobial resistance is necessary. Diet, probiotics/prebiotics, selective oropharyngeal or digestive decontamination, and especially fecal microbiota transplantation (FMT) are under investigation with FMT being the most studied. But, as prevention is better than cure, the implementation of antimicrobial stewardship programs and strict infection control measures along with newly developed chelating agents could also play a crucial role in decreasing colonization with multidrug resistant organisms. Conclusion: New alternative tools to fight antimicrobial resistance via gut microbiota modulation, seem to be effective and should remain the focus of further research and development.
... Although in primary studies the usefulness of the gut microbes was mostly considered in the gastrointestinal tract, however, it was found that, through production of a variety of bioactive substances, this intestinal flora impacts various body organs. Especially, the gut microbiota has a bidirectional communication with the nervous system called as the "microbiota-gut-brain axis" (Cryan and O'Mahony, 2011). This mutual connection occurs through several routs including neural, immune, metabolic and endocrine pathways (Novotny et al., 2019), and an intact gut microbiota is required for proper brain function . ...
Article
Full-text available
Introduction It is well known that the intestinal bacteria substantially affect physiological processes in many body organs. Especially, through a bidirectional communication called as gut-microbiota-brain axis, the gut microbiota deeply influences development and function of the nervous system. Hippocampus, as a part of medial temporal lobe, is known to be involved in cognition, emotion, and anxiety. Growing evidence indicates that the hippocampus is a target of the gut microbiota. We used a broad search linking the hippocampus with the gut microbiota and probiotics. Methods All experimental studies and clinical trials published until end of 2021 were reviewed. Influence of the gut microbiota on the behavioral, electrophysiological, biochemical and histological aspects of the hippocampus were evaluated in this review. Results The effect of disrupted gut microbiota and probiotic supplements on the microbiota-hippocampus link is also considered. Studies show that a healthy gut microbiota is necessary for normal hippocampus dependent learning and memory and synaptic plasticity. The known current mechanisms are production and modulation of neurotrophins, neurotransmitters and receptors, regulation of intracellular molecular processes, normalizing the inflammatory/anti-inflammatory and oxidative/antioxidant factors, and histological stability of the hippocampus. Activity of the hippocampal neuronal circuits as well as behavioral functions of the hippocampus positively respond to different mixtures of probiotic bacteria. Discussion Growing evidence from animal researches indicate a close association between the hippocampus with the gut microbiota and probiotic bacteria as well. However, human studies and clinical trials verifying such a link are scant. Since the most of papers on this topic have been published over the past 3 years, intensive future research awaits.
... 34,35 Importantly, gut microbiota dysbiosis is associated with GI symptoms and also the onset of cytokine induced sickness behaviours, such as lethargy, social withdrawal, anxiety, cognitive dysfunction and anhedonia. 34,36,37 Additionally, recent data suggest that in survivors, chemotherapy affects gut microbiota alpha diversity and taxonomic abundance after treatment has ended, and that certain bacteria are associated with psychosocial and GI symptoms. 19 Hence, chemotherapy induced dysbiosis of the gut microbiota may be one common mechanism by which patients experience comorbid GI symptoms and psychosocial problems following treatment. ...
Article
Full-text available
Background Cancer treatments, such as chemotherapy, may adversely affect gastrointestinal (GI), physical and mental health in survivors of cancer. Objective This study investigated associations between GI, mental and physical health outcomes, and cancer treatment-related variables, such as chemotherapy, in adult cancer survivors. Methods A one-time cross-sectional survey with patient-reported outcomes was used. Cancer survivors (N = 317) aged ≥18 years, living in Canada, who completed cancer treatments were included. Descriptive statistics, correlation, and linear regression analyses are reported. Results Mean age at diagnosis was 40.90 ± 15.40 years. Most survivors received chemotherapy (86.1%). Persistent GI symptoms include constipation (53.6%), diarrhea (50.5%), and bloating/pain (54.9%). Mean GI symptom duration was 30.53 ± 33.42 months. Severity of GI symptom interference was moderate to extreme for 51.9% of survivors. Compared to normative values of 50 in healthy people, survivors scored poorer for mental health (M = 42.72 ± 8.16) and physical health (M = 45.55 ± 7.93), and reported more belly pain (M = 56.10 ± 8.58), constipation (M = 54.38 ± 6.81), diarrhea (M = 55.69 ± 6.77), and gas/bloating (M = 56.08 ± 8.12). Greater GI symptom severity was associated with poorer mental and physical health ( P < .01). Chemotherapy was associated with increased belly pain ( B = 4.83, SE = 1.65, P < .01) and gas/bloating ( B = 3.06, SE = 1.45, P = .04). Conclusion We provide novel evidence that many cancer survivors experience chronic, moderate to severe GI symptoms lasting for years after cancer treatment, which are associated with worse mental and physical health. Chemotherapy is associated with specific GI symptoms. Integrative therapies are needed to address GI symptoms in cancer survivors.
... Known to modulate human host health, intestinal microbiota communicate bidirectionally with the central nervous system through various pathways along the gut-brain axis (GBA). Recent research shows the GBA can influence human host behavior, cognition, and emotions [14] which affects overall health and QOL. Reciprocally, fear of cancer recurrence has been associated with decreased microbial diversity in breast cancer survivors [15]. ...
Article
Full-text available
Purpose To investigate relationships between body size, gut microbiome, and health-related quality of life (QOL) in breast cancer survivors (BCS) in a clinical trial. Methods A cross-sectional substudy was conducted using baseline data from 70 BCS participating in a randomized controlled trial of a lifestyle intervention. Measures included anthropometrics, QOL (Short Form Health-related QOL Survey-36 [SF-36]), and 16S rRNA gene sequencing of fecal microbes. Participants were categorized by body mass index (BMI) into without obesity (≤ 29.9 kg/m²; n = 38) and with obesity (≥ 30.0 kg/m²; n = 32) groups. Differences in bacterial taxa between groups were assessed using Kruskal–Wallis one-way analysis of variance. Spearman and partial correlations explored associations between taxa and SF-36 subscales. Mediation analysis explored the relationship between BMI and SF-36 mental health summary score with alpha diversity as a mediator. Results Most BCS (72.9%) were non-Hispanic White with average age of 61.6 (± 8.7) years. No differences were observed for SF-36 subscales between groups. Physical functioning, vitality, and mental health subscales were negatively associated with Ruminococcus (ρ = − 0.304, p = 0.036; ρ = − 0.361, p = 0.012; ρ = − 0.495, p < 0.001) and Dorea (ρ = − 0.378, p = 0.028; ρ = − 0.33, p = 0.022; ρ = − 0.388, p = 0.006) abundance controlling for BMI. BCS without obesity had a significantly higher relative abundance of Ruminococcus (p = 0.003), Streptococcus (p = 0.049), Roseburia (p = 0.035), and Dorea (p = 0.003). Conclusions Fecal microbial composition differed between BCS with and without obesity, with associations between QOL and several microbial taxa. Several of these genera, previously identified as potentially beneficial, may also influence QOL in BCS. These results support further studies to determine the role of individual microbiota in QOL and obesity in cancer survivors.
... Puetz et al. [76] showed that the gut microbiome is associated with the fear of humans in the red jungle fowl. The ability of gut microbiota to communicate with the brain, possibly through neural, endocrine, and immune pathways, may modulate the behaviour of human beings and animals [77,78]. Probiotics benefit the host by improving GIT activities, thus regulating microbiota-gut-brain activity, including emotional and behavioural reactions [5,16,79]. ...
Article
Full-text available
Catching and crating may elicit stress and fear reactions in poultry because the procedures involve human contact and exposure to a novel environment. This study determined the effects of dietary probiotic supplementation on physiological stress, underlying fear, and growth performance of Pekin ducks subjected to catching and 4 h of crating. The study used a 2 × 2 factorial arrangement; the main factors were diet (basal or basal + probiotic) and crating durations (0 or 4 h). From 1 to 21 days of age (doa), birds were fed a basal or basal + probiotic (CLOSTAT® (Bacillus subtilis) (Kemin Industries, Inc., Des Moines, IA, USA), 1 g/kg) diet. At 21 doa, an equal number of ducklings from each dietary group were caught and crated for 4 h or left undisturbed in the home pens. Birds were examined for serum corticosterone (CORT), heat shock protein (HSP) 70, creatine kinase (CK), triglyceride (TG), glucose (GLU), cholesterol (CHOL), and lactate (LAC) concentrations, heterophil to lymphocyte ratios (HLR), tonic immobility (TI) duration, open-field (OF) test, body weight (BW), and feed conversion ratios (FCR). Diet had no significant (p > 0.05) effect on CORT among the non-crated ducks. However, after catching and crating, birds fed the control diet had significantly (p < 0.05) higher CORT than their probiotic-supplemented counterparts. Catching and crating significantly (p < 0.05) elevated HSP70, HLR, GLU, and CHOL but reduced TG in ducks. Birds fed the probiotic-supplemented diet showed significantly (p < 0.05) lower HSP70, HLR, TG, and CK than those fed the control diet. Probiotic-supplemented ducks showed reduced fear-related behaviours, including TI durations, ambulation latency, and body shaking. Diet had a negligible effect on body weights and FCR of ducks at 21 doa. In brief, catching and crating for 4 h augmented Pekin ducks’ physiological stress and fear reactions, and supplementing birds with probiotics was beneficial in ameliorating these detrimental effects.
... The microorganisms of the gut microbiome are communicating with the brain through the gut-brain axis [9]. A better understanding of the function of the microbiome has expanded the concept of the gut-brain axis to the microbiota-gut-brain axis, accentuating the importance of the microbiome in the gut-brain communication [10]. The microbiotagut-brain axis is controlled by several systems such as the central nervous system, the enteric nervous system and the autonomous nervous system and by neuroendocrine and neuroimmune pathways. ...
Article
Full-text available
The role of the gut microbiome in mental health has been of great interest in the past years, with several breakthroughs happening in the last decade. Its implications in several psychiatric disorders, namely anxiety, depression, autism and schizophrenia, are highlighted. In this review were included relevant studies on rodents, as well as human studies. There seems to be a connection between the gut microbiome and these pathologies, the link being emphasized both in rodents and humans. The results obtained in murine models align with the results acquired from patients; however, fewer studies regarding anxiety were conducted on humans. The process of sequencing and analyzing the microbiome has been conducted in humans for several other pathologies mentioned above. Additionally, the possible beneficial role of probiotics and postbiotics administered as an aid to the psychiatric medication was analyzed.
... Communication between the gut and brain is known as gut-brain axis [277]. Communication between the brain and gut involves neural pathways, such as the enteric nervous system (ENS), vagus, sympathetic, and spinal nerves, as well as humoral pathways involving cytokines, hormones, and neuropeptides as signaling molecules [278]. The ENS controls the functions of the gut and includes blood flow absorption, motility, and secretion, and these four compromise the main function of the gut-brain axis [267]. ...
Chapter
Full-text available
Autoimmune diseases have emerged as a pandemic in our modern societies, especially after World War II. There are currently more than 80 autoimmune diseases that compromise the lives of millions of patients around the world. There is a variety of factors that are involved in the pathogenesis of autoimmune diseases that vary from environmental factors to genetic susceptibility. The GI tract is one of the most susceptible subsystems in human bodies for autoimmune organ-specific diseases. There are five autoimmune GI tract diseases that are most common. This review consists of two chapters. In part I, we shed the light on introducing the concept of autoimmunity, the description of the disease's pathogenesis and the diagnosis, the link between the gut and brain through what is known as the gut-brain axis, and the relationship of this axis in GI autoimmune diseases. In part II, we will shed light on the role of antibodies as markers for the prediction of the disease, artificial intelligence in GI autoimmune diseases, the nutritional role and implications in the five GI autoimmune diseases, and finally the treatment of those diseases.
... Gut microbiota is composed of bacteria, fungi, protozoa, and archaea in the gastrointestinal tract, and their interactions with the host have been extensively investigated [15]. Gut microbiota is involved in many behavioral and physiological processes of the host [16,17], including aggressive behavior [14], the secretion of reproductive hormones (such as T and MT) [18][19][20], spermatogenesis [21], and physiological metabolism [22,23]. Dysbiosis of the microbial communities has been associated with male infertility in humans [24]. ...
Article
Full-text available
Background: Seasonal breeding in mammals has been widely recognized to be regulated by photoperiod, but the association of gut microbiota with photoperiodic regulation of seasonal breeding has never been investigated. Results: In this study, we investigated the association of gut microbiota with photoperiod-induced reproduction in male Brandt’s voles (Lasiopodomys brandtii) through a long-day and short-day photoperiod manipulation experiment and fecal microbiota transplantation (FMT) experiment. We found photoperiod significantly altered reproductive hormone and gene expression levels, and gut microbiota of voles. Specific gut microbes were significantly associated with the reproductive hormones and genes of voles during photoperiod acclimation. Transplantation of gut microbes into recipient voles induced similar changes in three hormones (melatonin, follicle-stimulating hormone, and luteinizing hormone) and three genes (hypothalamic Kiss-1, testicular Dio3, and Dio2/Dio3 ratio) to those in long-day and short-day photoperiod donor voles and altered circadian rhythm peaks of recipient voles. Conclusions: Our study firstly revealed the association of gut microbiota with photoperiodic regulation of seasonal breeding through the HPG axis, melatonin, and Kisspeptin/GPR54 system. Our results may have significant implications for pest control, livestock animal breeding, and human health management.
... The prevalence of MDD has been increasing along side rates of obesity and sugar consumption, which are also linked to inflammation (Ellulu et al., 2017;Greenberg et al., 2021;Stierman et al., 2021;Bentley et al., 2020). The link between gut biome and neuroscience has been a common topic relevant to behavioural consequences and psychological disorders for roughly the past decade (Cryan and O'Mahony, 2011;Lyte, 2013;Moulton et al., 2019). Hsu et al. (2015) used a rat model to find that overconsumption of sugars, specifically high fructose corn syrup (HFCS-55), induced hippocampal and metabolic dysfunction, as well as significant increases in IL-6 and interleukin-1β (IL-1β); especially when consumed during the adolescent period. ...
Article
Full-text available
Given that available antidepressant pharmacotherapies are not optimally effective, there is a need for alternative treatment options that are rooted in a comprehensive understanding of the illness's pathophysiology. Major depressive disorder (MDD) has been historically attributed to monoamine, i.e., serotonin (5-hydroxytryptamine, 5-HT) imbalance and some brain morphological pathologies that have directed treatment towards particular medications that are only minimally effective. MDD pathophysiologies have now been regarded as linked to chronic inflammation and MDD can be treated with compounds that have anti-inflammatory properties. Individuals vulnerable to MDD have increased baseline neuroinflammatory response that is exacerbated by psychogenic stress. When pro-inflammatory mechanisms are chronically hyperactive, dysfunction of brain-related processes occur. We propose that inflammation is one of the primary mechanisms that trigger biological changes leading to MDD. Inflammatory resolution occurs when homeostasis is achieved after an inflammatory response. However, cascading biological events are likely to prevent resolution from occurring and worsen both inflammation and MDD. Novel and alternative pharmacotherapies—e.g., ketamine, cannabinoids, and psychedelics—provide a richer mechanistic perspective on the role of neuroinflammation and neuroprogression by means of rapid, short-term, and long-term symptom relief potentially based on their anti-inflammatory properties. These drugs ultimately decrease proinflammatory cytokine levels that correspond with improved symptoms. However, it is unclear what differentiates these compounds from others in their mechanistic efficacy. Thus, a closer investigation into their anti-inflammatory effects is imperative in order to better elucidate the link between MDD and inflammation, as well as uncover the mechanisms involved in long-term symptom reduction of MDD.
... Not only does the gut microbiome help to maintain gastrointestinal (GI) homeostasis, but the microbiota have important influences on the rest of the body and the brain (Dantzer et al., 2008;Duerkop et al., 2009;Forsythe and Bienenstock, 2010;Cryan and Dinan, 2012). For example, there is bidirectional communication between the gut and the central nervous system (CNS), with the microbiota considered to be essential for the development of the immune system and playing a major role in influencing the nervous system (Cryan and O'Mahony, 2011;Bhuiyan et al., 2021) via bacterial metabolites (Kaur et al., 2019), neurotransmitters (Barrett et al., 2012;Erny et al., 2015) and short-chain fatty acids (SCFAs) (Hoyles et al., 2018;Spichak et al., 2021). In turn, the CNS has a critical role in modulating gut-related metabolism and physiology via the vagus nerve (Wang et al., 2002;Miyauchi et al., 2022). ...
Article
Full-text available
Since the first model of experimental autoimmune encephalomyelitis (EAE) was introduced almost a century ago, there has been an ongoing scientific debate about the risks and benefits of using EAE as a model of multiple sclerosis (MS). While there are notable limitations of translating EAE studies directly to human patients, EAE continues to be the most widely used model of MS, and EAE studies have contributed to multiple key breakthroughs in our understanding of MS pathogenesis and discovery of MS therapeutics. In addition, insights from EAE have led to a better understanding of modifiable environmental factors that can influence MS initiation and progression. In this review, we discuss how MS patient and EAE studies compare in our learning about the role of gut microbiome, diet, alcohol, probiotics, antibiotics, and fecal microbiome transplant in neuroinflammation. Ultimately, the combination of rigorous EAE animal studies, novel bioinformatic approaches, use of human cell lines, and implementation of well-powered, age- and sex-matched randomized controlled MS patient trials will be essential for improving MS patient outcomes and developing novel MS therapeutics to prevent and revert MS disease progression.
... As it is often the case in Science, it is mainly nitive function and brain development [12]. Without 116 further ado, let's see now what the nature of this com-117 munication between microbiome and brain might be. ...
Article
Full-text available
Understanding the brain is not only intrinsically fascinating to apprehend life’s complexity or to further progress in fundamental biosciences, but it is also highly relevant to increase our well-being since the brain exhibits a power over the body that makes it capable both of triggering illness or facilitating the healing process. Considering the dual role at play by the brain, using ascending and descending pathways to combine information issued from the external world and the internal environment, this review challenges the cerebro-centered vision of the brain. In our daily life, we construct a representation of the outside world by transforming chemical, pressure changes, and light waves into tastes, smells, touches, sounds and sights. In doing so, we create our experience of the external world by interpreting our senses through a process called exteroception. But to be compelling, this Descartes’ vision of the brain has to be completed by integration of events from inside our body. The way the brain constructs our inner sensations called interoception, is now starting to be unrevealed. As such, brain sciences have undergone, and will undergo, an important revolution, redefining its boundaries beyond the skull to prefer a more holistic vision carried out by the notion of an embodied brain acting as a coincidence detector to combine sensory experiences with corporeal homeostasis. The goal of this review is to highlight some mechanisms by which the brain activity is controlled by internal cues for better prediction. The gut-brain axis is here taken as a canonical example to discuss about the communication between the milieu intérieur and brain functions that shapes how we feel, and how we think.
... A commonly occurring claim is that LGG and other probiotics can restore a dysbiotic microbiome by recovering the diversity and richness typical of healthy gut microbiota [5]. Dysbiosis is associated with many diseases, including chronic autoimmune inflammatory diseases [6,7], Crohn's disease, chronic diarrhea of the lower bowel [8][9][10][11][12][13][14], cardiovascular diseases [15,16], diabetes, and obesity [17][18][19], as well as stress and anxiety [20][21][22][23][24]. In contrast, some clinical trials and in vivo experiments on animal models have reported probiotics to be ineffective or to even have contradictory outcomes and ascribing side effects with LGG use, such as brain fogginess [25], inefficiency as treatment of acute [26], ileal pouch inflammation [27], and increased incidence of bacteremia, endocarditis, and sepsis-induced dysbiosis [3,28]. ...
Article
Full-text available
The consumption of probiotics is widely encouraged due to reports of their positive effects on human health. In particular, Lacticaseibacillus rhamnosus strain GG (LGG) is an approved probiotic that has been reported to improve health outcomes, especially for gastrointestinal disorders. However, how LGG cooperates with the gut microbiome has not been fully explored. To understand the interaction between LGG and its ability to survive and grow within the gut microbiome, this study introduced LGG into established microbial communities using an in vitro model of the colon. LGG was inoculated into the simulated ascending colon and its persistence in, and transit through the subsequent transverse and descending colon regions was monitored over two weeks. The impact of LGG on the existing bacterial communities was investigated using 16S rRNA sequencing and short-chain fatty acid analysis. LGG was able to engraft and proliferate in the ascending region for at least 10 days but was diminished in the transverse and descending colon regions with little effect on short-chain fatty acid abundance. These data suggest that the health benefits of the probiotic LGG rely on its ability to transiently engraft and modulate the host microbial community.
... Gut microbiota regulates anxietylike and depression-like behavior: Evidences from animal studies Despite the limitations represented mainly by the difference in the composition of the human and murine microbiota, and the difficulty of translate the findings from experimental models to patients where no complete ablation of the microbiota can be achieved, studies on rodents indicate that gut microbiota influences brain function and may impact on the behavior (10). Experimental approaches used to study the microbiotagut-brain axis included the treatment with probiotics/antibiotics, the induction of gut inflammation by injection of enteric bacterial pathogens, the use of germ-free (GF)/gnotobiotic animals and the human diseases-related fecal microbiota transplantation (FMT) (11). The main advantages of studies performed on murine experimental models are the efficacy of behavioral tests to reveal changes similar to what observed in patients affected by anxiety or depression (12), and the possibility to analyze the effects of a single bacterial phylum or species on behavior. ...
Article
Full-text available
Depression and anxiety disorders represent a burdensome clinical issue. Considering the unsatisfactory clinical response of some patients to antidepressant therapy, new personalized approaches are being studied. In recent years, pre-clinical and clinical studies have investigated the role of intestinal microbiota demonstrating the importance of the gut-brain axis in these diseases. Indeed, gut microbes are able to interact with the brain interfering with behavior through some mechanisms such as amino acid metabolism, short–chain fatty acids, vagus nerve, endocrine signaling and immune responses. Experiments of gut microbiota transfer from subjects with major depression to animal models corroborated the causative role of intestinal microbes in mood disorders and anxiety. Furthermore, the incidence of dysbiosis in patients with anxiety and depression suggests a potential role for gut microbiota modulators in the treatment of these disorders. In particular, several probiotics and synbiotics have been shown to be effective in improving clinical symptoms, promising results have emerged also from fecal microbiota transplantation, but the evidence is still limited. These promising results switch on the use of gut microbiota modulators as an adjunctive tool to anti-depressant therapy. Developing pharmaceutical or nutraceutical strategies to modify the composition of gut microbiota may offer novel and personalized therapeutic tools against anxiety and depression.
... Age-related changes to the microbiome include decrease in microbial diversity, increase in pathobionts, and increased gut permeability (Falony et al., 2016;Elderman et al., 2018). Changes in the composition of the microbiome are associated with the development of obesity and related metabolic disorders (Ley, 2010;Tilg and Kaser, 2011), maintenance of gut barrier integrity (Turner, 2009;Jandhyala et al., 2015;Gwak and Chang, 2021), intestinal pro-and antiinflammatory balance (Desai et al., 2016;Bolte et al., 2021), immune and cardio-metabolic health (Hansen et al., 2015;Loṕez et al., 2016;Sanchez-Alcoholado et al., 2017), and homeostasis of the gut-brain axis (Rhee et al., 2009;Cryan and O'Mahony, 2011;Lyte, 2013). To date, a large body of evidence has shown that older people maintain a compositionally distinct microbiota as compared with younger adults; these changes are associated with gradients in clinical frailty and inflammatory status (O'Toole and Jeffery, 2018). ...
Article
Full-text available
The microbiome and immune system have a unique interplay, which influences homeostasis within the organism. Both the microbiome and immune system play important roles in health and diseases of the aged including development of cancer, autoimmune disorders, and susceptibility to infection. Various groups have demonstrated divergent changes in the gut microbiota during aging, yet the compounding factor of biological sex within the context of aging remains incompletely understood, and little is known about the effect of housing location in the composition of gut microbiota in the context of both sex and age. To better understand the roles of sex, aging, and location in influencing the gut microbiome, we obtained normal healthy BALB/cByJ mice from a single source and aged male and female mice in two different geographical locations. The 16S rRNA was analyzed from fecal samples of these mice and cytokine levels were measured from serum. 16S rRNA microbiome analysis indicated that both age and sex play a role in microbiome composition, whereas location plays a lesser role in the diversity present. Interestingly, microbiome changes occurred with alterations in serum expression of several different cytokines including IL-10 and IL-6, which were also both differentially regulated in context to sex and aging. We found both IL-10 and IL-6 play a role in the constitutive expression of pSTAT-3 in CD5+ B-1 cells, which are known to regulate the microbiome. Additionally, significant correlations were found between cytokine expression and significantly abundant microbes. Based on these results, we conclude aging mice undergo sex-associated alterations in the gut microbiome and have a distinct cytokine profile. Further, there is significant interplay between B-1 cells and the microbiome which is influenced by aging in a sex-dependent manner. Together, these results illustrate the complex interrelationship among sex, aging, immunity, housing location, and the gut microbiome.
... The gut-brain axis has been shown to have a crucial role in maintaining intestinal homeostasis and brain function. 73,74 The intestinal microbiome affects communication between the intestines and the brain through immune, endocrine and neural pathways, 75 and evidence suggests that it significantly impacts brain function affecting mood, recognition and behavior. 76 Probiotics have been shown to modulate hippocampus-mediated negative feedback regulation of the hypothalamic-pituitary-adrenal axis, mitigate stress-induced pain and behavior, 77,78 transduce signals to the brain via the afferent vagal nerve and relieve mood disturbances. ...
Article
Full-text available
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.
... Microbiota actively participates in maintaining a healthy state of the organism in adulthood, and its quantitative and qualitative changes may lead to dysbiosis and disease development [2,13]. To date, a number of functions have been associated with the core microbiome, including polysaccharide digestion, immune system development, protection against infection, vitamin synthesis, fat storage, angiogenesis regulation and behavioral development [14,15,16,17]. Interestingly, the genes encoded by the human core microbiome encode proteins necessary for the survival of the host but absent from the human genome, this discovery led to the definition of the microbiome as "our forgotten organ" [18]. ...
Article
Full-text available
The health of the human body is influenced by many external and internal factors, but one of the most important of them is the rich microbiota of the human body. The number of microorganism cells inhabiting the human body exceeds the number of cells that make up the human body. Several different ecosystems coexist in the human body, incl. microbiota of the skin, eye, respiratory tract, urogenital tract and gastrointestinal tract. The composition of microbiota in various parts of the human body, as well as in various parts of a given system or organ, differs significantly from one another. Detailed knowledge of the composition of the human microbiota, as well as its functions for the host organism, is a starting point for further considerations on the meaning of dysbiosis, i.e. changes in the composition of the microbiota, for changing the functioning of the microbiota-host relationship and the development of disease states. It seems that further scientific research on this topic will lead to the recognition of microbiota as a marker and diagnostic tool, and possibly a past therapeutic target for some diseases. This publication attempts to organize and summarize basic information on the human gastrointestinal tract microbiota (GIT microbiota) in health.
... 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). ...
Article
Full-text available
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 .
... 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). ...
Article
Full-text available
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.
... 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]. ...
Article
Full-text available
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.
... The microbiome, the combination of all the microorganisms in a host, has been associated with numerous disease and functional phenotypes in humans (Cho and Blaser, 2012). Studies have examined the microbiome's role in the gut-brain axis, cancer risk, digestion, obesity, immune modulation, drug metabolism, as well as risk for disease or dysfunction (Blacher et al., 2017;Cryan and O'Mahony, 2011;Helmink et al., 2019;Lawrence and Hyde, 2017;Ley, 2010;Zimmermann et al., 2019). Microbiome analyses rely on the identification of the microorganisms within a given sample. ...
Article
Full-text available
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
Full-text available
The central nervous system (CNS) and the gastro-intestinal tract (GIT) form numerous connections that are often referred to in the scientific literature as the brain-gut axis. It includes structures from the enteric nervous system, the sympathetic nervous system and the spinal nerves, the vagus nerve and the endocrine system. A number of neurotransmitters and hormones take part in the formation of the nexuses of the brain-gut axis, one of them being serotonin (5-hydroxytrypt-amine, 5-HT). 5-HT is a neurotransmitter synthesized from tryptophan in the serotonergic neurons of the CNS (10%) and the enterochromaffin cells of the GIT (90%). A number of publications point to the contribution of the intestinal microflora-in particular anaer-obic bacteria, such as Turicibacter sanguinis, Akker-mansia muciniphila, Lactobacillus plantarum, Lac-tobacillus Rhamnosus, and other bacteria of the normal gut microbiome, in the regulation of the levels of 5-HT in the GIT and the brain-gut axis. The coloniza-tion of the GIT with pathogenic bacteria and dysbac-teriosis can cause dysregulation in the brain gut-axis , which in turn can affect the function of the CNS. Research shows that such dysregulations take part in the pathogenesis of a number of gastrointestinal diseases (inflammatory bowel disease) and neuropsychi-atric disorders (depression, anxiety and panic disorders , autism and multiple sclerosis). The aim of our research is to review the existing scientific literature
Article
Full-text available
The gut microbiota plays a key role in the function of the host immune system and neuroimmune diseases. Alterations in the composition of the gut microbiota can lead to pathology and altered formation of microbiota-derived components and metabolites. A series of neuroimmune diseases, such as myasthenia gravis (MG), multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSDs), Guillain–Barré syndrome (GBS), and autoimmune encephalitis (AIE), are associated with changes in the gut microbiota. Microecological therapy by improving the gut microbiota is expected to be an effective measure for treating and preventing some neuroimmune diseases. This article reviews the research progress related to the roles of gut microbiota and fecal microbiota transplantation (FMT) in neuroimmune diseases.
Article
Microorganisms in human life play a huge role: in particular, those that coexist with the host organism, inhabiting the skin, upper respiratory tract, external genitalia and especially the digestive tract. The intestinal microbiota, including bacteriome, mycobiome and virome, not only takes part in the digestion process, but also provides the synthesis of a number of vitamins. The intestinal microbiome also serves as the basis for a system of extensive bidirectional neuroendocrine pathways that connect microbiota with various regions of the central nervous system, the hypothalamic-pituitary-adrenal system, and the peripheral parts of the autonomic nervous system. This system of connections has got the name of gut-brain axis and has attracted close attention of scientists over the past two decades, since a targeted impact on the intestinal flora is potentially capable of changing the nature of nervous system regulatory influences on the whole body. It is especially important to study patterns of functioning of the gut-brain axis in patients with the nervous system pathology, namely neurodegenerative and demyelinating diseases. Methods for their treatment continue to improve, and perhaps the correction of the gut microbiotic composition will serve as an additional therapeutic approach. The review article describes current views on the role of the intestinal microbiota, provides the latest data on the composition of bacteriome, mycobiome, and virome in patients with relapsing-remitting multiple sclerosis.
Book
Full-text available
Sağlıklı yaşam
Chapter
Multiple sclerosis (MS) is a chronic neurodegenerative disorder whose etiology is not fully understood. Genetic factors, environmental factors, and eating habits are involved in the onset and development of the disease. Alterations in the gut microbiota are related to MS development since various studies directly relate it to the immune system and its protection against infections. The complex intestinal microbiota has not yet been fully understood. In particular, dysbiosis has been found in MS, especially in species that produce butyrate, propionate, and short-chain fatty acids, among other bacterial products or metabolites. On the other hand, the virome is one of the most studied, especially Epstein–Barr, Herpes Virus, retrovirus, Rubella, and Varicella-Zoster, some of the most related to multiple sclerosis. This chapter discusses the role of the microbiota and its pathogenesis and management in Multiple Sclerosis.
Article
The aim of this study is to examine the effect of gut microbiota on brain functions, mood and psychiatric disorders such as depression, anxiety and behavioral addictions, neurotransmitter levels, cognitive processes such as self-control, decision making and delayed gratification. In this context, the relevant literature was reviewed and the findings were evaluated. The relationships of the bidirectional communication between the brain-gut axis with cognitive, emotional, behavioral and physiological processes were explained with a diagram. As a result, although more research is needed on this subject, it has been observed that the brain-gut axis is bidirectionally established through neural, stress, endocrine and immune systems. In this bidirectional communication process, there are interactions in the context of cognitive, emotional, behavioral and other physiological factors. These factors both individually enter into bidirectional relationships with the brain and gut microbiota and are affected by the bidirectional communication between the brain and gut.
Article
Full-text available
Recent studies, using high resolution magnetoencephalography (MEG) and electrogastrography (EGG), have shown that during resting state, rhythmic gastric physiological signals are linked with cortical brain oscillations. Yet, gut-brain coupling has not been investigated with electroencephalography (EEG) during cognitive brain engagement or during hunger-related gut engagement. In this study in 14 young adults (7 females, mean ± SD age 25.71 ± 8.32 years), we study gut-brain coupling using simultaneous EEG and EGG during hunger and satiety states measured in separate visits, and compare responses both while resting as well as during a cognitively demanding working memory task. We find that EGG-EEG phase-amplitude coupling (PAC) differs based on both satiety state and cognitive effort, with greater PAC modulation observed in the resting state relative to working memory. We find a significant interaction between gut satiation levels and cognitive states in the left fronto-central brain region, with larger cognitive demand based differences in the hunger state. Furthermore, strength of PAC correlated with behavioral performance during the working memory task. Altogether, these results highlight the role of gut-brain interactions in cognition and demonstrate the feasibility of these recordings using scalable sensors.
Article
Full-text available
Introdução: Os transtornos de ansiedade e depressão atingem boa parte da população e suas causas são variadas. Uma delas é a alimentação inadequada. Em geral, a ingestão de frutas, vegetais e fibras está associada à riqueza e diversidade da microbiota, enquanto o aumento da ingestão de alimentos processados (ricos em gordura e açúcar) aumenta o risco de doenças inflamatórias crônicas, como a depressão. Objetivo: descrever a influência da nutrição no tratamento e prevenção dos transtornos mentais: ansiedade e depressão. Metodologia: revisão bibliográfica de caráter descritivo e qualitativo. Resultados: indivíduos com estes transtornos apresentam deficiências nutricionais de determinadas substâncias e, com alimentação adequada, podem se recuperar dos quadros depressivos e de ansiedade. Conclusão: existe relação direta entre o que ingerimos e a saúde mental e a alimentação auxiliam no tratamento destes transtornos.
Article
Full-text available
Science teaching has been guided by different trends that are still used in the classroom today. More recently, the concern with developing experimental activities began to have a strong presence in teaching projects and teacher training courses. In the municipality of Abaetetuba-PA, located in the Amazon, most education professionals do not pay attention to the fact that everyday situations are directly linked to scientific knowledge. This article was intended to approach methodological actions of everyday life at school, seeking support in the empirical knowledge of students so that they can use the academic knowledge acquired in the classroom to understand and solve problems of daily life. The socioeconomic characteristics of the students were analyzed and ten experiments in the area of science were related to daily life, to the syllabus, and applied to 60 students from the 4th grade of an elementary school in the municipal education network (public) and in a private school. All experiments applied with this methodology had widespread acceptance among students and proved to be effective in students' performance. Through the ANOVA calculation, it was found that there were no significant differences for most of the answers between the students of the two schools.
Article
Full-text available
O presente trabalho busca descrever os aspectos que asseveram o quadro de disbiose intestinal e, consequentemente, o acometimento de depressão e como a modulação intestinal pode colaborar com a melhoria da qualidade de vida de pacientes. A possibilidade de aprofundamento desse estudo colabora com pesquisas que visam reduzir os impactos do desequilíbrio da microbiota na relação do eixo intestino-cérebro. A metodologia consta consiste em uma revisão sistemática de coletas de dados, a partir de pesquisa bibliográfica, na produção publicada em bases da LILACS, PubMed e Google Acadêmico. Estudos apontam que o uso de probióticos e simbióticos de forma prolongada pode afetar positivamente o humor, o fenótipo relacionado à ansiedade e depressão, modular o eixo hipotálamo-pituitária-adrenal, alterar a atividade cerebral e aumentar o neurotransmissor inibitório GABA, reduzindo assim sintomas de ansiedade e depressão. Entretanto, ressalta-se a necessidade de novos estudos para maior controle das variáveis (alimentação, exercícios, grau da depressão). Desta forma, esse recorte científico ressalta um caminho para que a sociedade enfrente os distúrbios relacionados entre cérebro e intestino, destacando-se que estratégias modulatórias podem auxiliar, consideravelmente, na melhora da qualidade de vida dos pacientes afetados pela depressão.
Article
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.
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: Primary biliary cholangitis (PBC) is a cholestatic liver disease characterized by non-suppurative destructive cholangitis of the small intrahepatic bile ducts and female preponderance. Chronic fatigue, a condition marked by extreme tiredness and inability to function because of a lack of energy, is the most common symptom in PBC, affecting up to 80% of patients. However, the pathogenesis of PBC-associated fatigue is unknown, and treatment outcomes are poor. Purpose: We aim to provide an updated summary of pathogenesis and emerging treatments for fatigued PBC patients. Methods: We conducted a structured literature survey and compiled a narrative review. Results: Fatigue is often the most bothersome symptom in PBC patients and is frequently accompanied by cognitive impairment, depressive symptoms, and anxiety. Fatigue is an independent predictor of mortality in PBC. The pathophysiology of these phenomena is complex and poorly understood; therefore, a causal treatment is lacking. Multiple lines of evidence point towards biological, psychological, and social factors that are underlying and modulating the disease burden in fatigued PBC patients. Animal models suggest that an inflammatory liver-brain axis is implicated in the pathogenesis of cholestatic fatigue. The currently available management options for fatigue and cognitive symptoms are mainly supportive. However, specific medical treatment options for relieving fatigue symptoms emerge, including anti-inflammatory treatments. Conclusion: Emerging pathophysiological concepts and experimental therapies may improve outcomes of fatigued PBC patients in the near future.
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.
Article
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
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
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.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
Irritable bowel syndrome (IBS) is a common disorder with widespread prevalence. Due to its heterogeneous pathogenesis, efficacious treatments are lacking. The few medications that are effective for treating global IBS symptoms have either been withdrawn or restricted due to detrimental side effects; thus, safe and effective alternatives are urgently needed. Increasing data have revealed that inflammatory changes may play a role in the development of IBS, and probiotics, commensal organisms with inherent health benefits, may alter that milieu. Although their exact mechanisms of action remain elusive, it is clear that the beneficial properties inherent to each probiotic species are strain specific. Bifidobacterium infantis 35624 ( B infantis 35624; Bifantis, The Procter & Gamble Company, Cincinnati, OH), is a probiotic with unique abilities to reduce intestinal inflammation. Two randomized, controlled trials have validated its efficacy for treating both individual and global IBS symptoms without evidence to suggest an increase in adverse events. B. infantis 35624 appears safe and effective for the treatment of IBS.
Article
Full-text available
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.
Article
Full-text available
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
Article
Full-text available
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.
Article
Full-text available
Monkeys with lesions limited to the hippocampal region (the hippocampus proper, the dentate gyrus, and the subiculum) were impaired on two tasks of recognition memory: delayed nonmatching to sample and the visual paired-comparison task. Recognition memory was impaired in five different groups of monkeys, whether the lesions were made by an ischemic procedure, by radio frequency, or by ibotenic acid. The finding that the hippocampal region is essential for normal recognition memory performance is considered in the context of current ideas about the role of the hippocampus in declarative memory.
Article
Full-text available
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. 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. 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 to 1.4+/-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. 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.
Article
Full-text available
The mechanism of the apparent anti-inflammatory action of probiotic organisms is unclear. Lactobacillus reuteri is effective in inhibiting colitis in interleukin-10 (IL-10)-deficient mice. Nerve growth factor (NGF), in addition to its activity on neuronal cell growth, has significant anti-inflammatory effects in several experimental systems in vitro and in vivo, including a model of colitis. Our experiments were designed to explore the mechanism of effect of L. reuteri in the human epithelial cell lines T84 and HT29 on cytokine and NGF synthesis and IL-8 response to tumor necrosis factor alpha (TNF-α). Epithelial cells were cultured for various times with live and killed L. reuteri and examined by reverse transcription-PCR for NGF, IL-10, and TNF-α-induced IL-8 expression. An enzyme-linked immunosorbent assay was used to quantitate intracellular IL-8 and secreted product. Western blotting and confocal microscopy were used to determine the effects on IκB and NF-κB, respectively. Live but not heat-killed or gamma-irradiated L. reuteri upregulated NGF and dose dependently inhibited constitutive synthesis by T84 and HT29 cells of IL-8 and that induced by TNF-α in terms of mRNA and intracellular and secreted protein. Similarly, L. reuteri inhibited IL-8 synthesis induced by Salmonella enterica serovar Typhimurium. L. reuteri required preincubation and adherence for effect, inhibited translocation of NF-κB to the nuclei of HeLa cells, and prevented degradation of IκB. Neither cellular lysates nor media supernatants had any effect on TNF-α-induced IL-8. The conclusion is that L. reuteri has potent direct anti-inflammatory activity on human epithelial cells, which is likely to be related to the activity of ingested probiotics. L. reuteri also upregulates an unusual anti-inflammatory molecule, NGF, and inhibits NF-κB translocation to the nucleus.
Article
Full-text available
Major depressive disorder (MDD) is an extremely complex and heterogeneous condition. Emerging research suggests that nutritional influences on MDD are currently underestimated. MDD patients have been shown to have elevated levels of pro-inflammatory cytokines, increased oxidative stress, altered gastrointestinal (GI) function, and lowered micronutrient and omega-3 fatty acid status. Small intestinal bacterial overgrowth (SIBO) is likely contributing to the limited nutrient absorption in MDD. Stress, a significant factor in MDD, is known to alter GI microflora, lowering levels of lactobacilli and bifidobacterium. Research suggests that bacteria in the GI tract can communicate with the central nervous system, even in the absence of an immune response. Probiotics have the potential to lower systemic inflammatory cytokines, decrease oxidative stress, improve nutritional status, and correct SIBO. The effect of probiotics on systemic inflammatory cytokines and oxidative stress may ultimately lead to increased brain derived neurotrophic factor (BDNF). It is our contention that probiotics may be an adjuvant to standard care in MDD.
Article
Full-text available
The present study tested whether individual differences in anxiety- and fear-related behaviour are associated with between-subjects variation in postmortem brain levels of selected neurotrophic factors. Naïve C57BL6/J mice of both sexes were subjected either to an elevated plus maze test or to a Pavlovian fear conditioning paradigm. Two days after behavioural assays, the mice were sacrificed for postmortem quantification of the protein levels of brain derived neurotrophic factors (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3) in the hippocampus and amygdala. Significant correlations between behavioural measures and postmortem regional neurotrophic factor contents were revealed. The magnitude of anxiety-like behaviour in the elevated plus maze was positively related to dorsal hippocampal BDNF levels, but negatively related to NGF levels in dorsal hippocampus and in the amygdala. On the other hand, the expression of conditioned fear is positively related to amygdala BDNF and NGF levels, and to dorsal hippocampal NGF levels. Our results add to existing reports in human as well as in animals of correlation between anxiety trait and gross measures of hippocampal volume or activation levels. Moreover, a distinction between spontaneous and learned (or conditioned) anxiety/fear would be relevant to the identification of neurotrophin signalling mechanisms in the hippocampus and amygdala implicated in anxiety and related psychopathology.
Article
Full-text available
Enteric infections, with or without overt diarrhea, have profound effects on intestinal absorption, nutrition, and childhood development as well as on global mortality. Oral rehydration therapy has reduced the number of deaths from dehydration caused by infection with an enteric pathogen, but it has not changed the morbidity caused by such infections. This Review focuses on the interactions between enteric pathogens and human genetic determinants that alter intestinal function and inflammation and profoundly impair human health and development. We also discuss specific implications for novel approaches to interventions that are now opened by our rapidly growing molecular understanding.
Article
Full-text available
Stress has been shown to have both central and peripheral effects, promoting psychological illness (such as anxiety and depression), as well influencing peripheral disease in the intestine. Stress in humans can exacerbate symptoms of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), lowering visceral pain thresholds and decreasing mucosal barrier function. Studies in rodents have revealed that both acute and chronic exposure to stressors can lead to pathophysiology of the small and large intestine, including altered ion secretion and increased epithelial permeability (by both transcellular and paracellular pathways). Prolonged exposure to stress can induce low-grade inflammation, cause ultrastructural epithelial abnormalities, and alter bacterial-host interactions allowing greater microbial translocation. In this review, we discuss the stress response and the effects of both acute and chronic stress to induce pathophysiological damage to the gut. We present the potential pathways involved, and the proposed mechanisms of action mediating the effects. Furthermore, we explore the impact of early life stress on colonic physiology in neonatal rodents and the implications for gut dysfunction in adulthood.
Article
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.
Article
There is a bidirectional relation between the central nervous system and the digestive tract, i.e., the brain-gut axis. Numerous data argue for a dysfunction of the brain-gut axis in the pathophysiology of irritable bowel syndrome (IBS). Visceral hypersensitivity is a marker of IBS as well as of an abnormality of the brain-gut axis. This visceral hypersensitivity is peripheral and/or central in origin and may be the consequence of digestive inflammation or an anomaly of the nociceptive message treatment at the spinal and/or supraspinal level. Stress is involved in the genesis and maintenance of IBS. Disturbances of the autonomic nervous system are observed in IBS as a consequence of brain-gut axis dysfunction. The contribution of the neurosciences, in particular brain imaging techniques, has contributed to the better understanding of IBS physiopathology. The better knowledge of brain-gut axis dysfunction has therapeutic implications, either through drugs and/or cognitive and behavioral therapies.
Article
Indigenous microbiota have several beneficial effects on host physiological functions; however, little is known about whether or not postnatal microbial colonization can affect the development of brain plasticity and a subsequent physiological system response. In a series of experiments using germ-free (GF), specific pathogen-free (SPF), and gnotobiotic mice, we recently demonstrated that gut microbes could affect the development of hypothalamic-pituitary-adrenal (HPA) reaction to stress. In this study, in order to further verify these findings, we performed glucocorticoid-suppression test in GF and SPF mice. In addition, norepinephrine (NE), serotonin (5-HT), and γ-aminobutyric acid (GABA) levels in various lesions of the brain were measured in both groups of mice. As a result, corticosterone pretreatment dose-dependently suppressed plasma ACTH response to restraint stress to a significantly lesser extent in GF mice than in SPF mice. GF mice exhibited increased NE and 5-HT levels in the cortex and hippocampus relative to SPF mice, although there was no difference in GABA concentration in any parts of the brain between either group of mice. These results further support the concept that the series of events in the gastrointestinal tract following postnatal microbial colonization can have a long-lasting impact on the neural processing of sensory information regarding the endocrine–stress axis.
Article
There is a bidirectional relation between the central nervous system and the digestive tract, i.e., the brain-gut axis. Numerous data argue for a dysfunction of the brain-gut axis in the pathophysiology of irritable bowel syndrome (IBS). Visceral hypersensitivity is a marker of IBS as well as of an abnormality of the brain-gut axis. This visceral hypersensitivity is peripheral and/or central in origin and may be the consequence of digestive inflammation or an anomaly of the nociceptive message treatment at the spinal and/or supraspinal level. Stress is involved in the genesis and maintenance of IBS. Disturbances of the autonomic nervous system are observed in IBS as a consequence of brain-gut axis dysfunction. The contribution of the neurosciences, in particular brain imaging techniques, has contributed to the better understanding of IBS physiopathology. The better knowledge of brain-gut axis dysfunction has therapeutic implications, either through drugs and/or cognitive and behavioral therapies.
Article
There is increasing interest in the gut-brain axis and the role intestinal microbiota may play in communication between these two systems. Acquisition of intestinal microbiota in the immediate postnatal period has a defining impact on the development and function of the gastrointestinal, immune, neuroendocrine and metabolic systems. For example, the presence of gut microbiota regulates the set point for hypothalamic-pituitary-adrenal (HPA) axis activity. We investigated basal behavior of adult germ-free (GF), Swiss Webster female mice in the elevated plus maze (EPM) and compared this to conventionally reared specific pathogen free (SPF) mice. Additionally, we measured brain mRNA expression of genes implicated in anxiety and stress-reactivity. Germ-free mice, compared to SPF mice, exhibited basal behavior in the EPM that can be interpreted as anxiolytic. Altered GF behavior was accompanied by a decrease in the N-methyl-D-aspartate receptor subunit NR2B mRNA expression in the central amygdala, increased brain-derived neurotrophic factor expression and decreased serotonin receptor 1A (5HT1A) expression in the dentate granule layer of the hippocampus. We conclude that the presence or absence of conventional intestinal microbiota influences the development of behavior, and is accompanied by neurochemical changes in the brain.
Article
Early life stress has been implicated in many psychiatric disorders ranging from depression to anxiety. Maternal separation in rodents is a well-studied model of early life stress. However, stress during this critical period also induces alterations in many systems throughout the body. Thus, a variety of other disorders that are associated with adverse early life events are often comorbid with psychiatric illnesses, suggesting a common underlying aetiology. Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is thought to involve a dysfunctional interaction between the brain and the gut. Essential aspects of the brain-gut axis include spinal pathways, the hypothalamic pituitary adrenal axis, the immune system, as well as the enteric microbiota. Accumulating evidence suggest that stress, especially in early life, is a predisposing factor to IBS. The objective of this review was to assess and compile the most relevant data on early life stress and alterations at all levels of the brain gut axis. In this review, we describe the components of the brain-gut axis individually and how they are altered by maternal separation. The separated phenotype is characterised by alterations of the intestinal barrier function, altered balance in enteric microflora, exaggerated stress response and visceral hypersensitivity, which are all evident in IBS. Thus, maternally separated animals are an excellent model of brain-gut axis dysfunction for the study of disorders such as IBS and for the development of novel therapeutic interventions.
Article
The concept that intestinal microbial composition not only affects the health of the gut, but also influences centrally-mediated systems involved in mood, is supported by a growing body of literature. Despite the emergent interest in brain-gut communication and its possible role in the pathogenesis of psychiatric disorders such as depression, particularly subtypes with accompanying gastrointestinal (GI) symptoms, there are few studies dedicated to the search for therapeutic solutions that address both central and peripheral facets of these illnesses. This study aims to assess the potential benefits of the probiotic Bifidobacterium infantis in the rat maternal separation (MS) model, a paradigm that has proven to be of value in the study of stress-related GI and mood disorders. MS adult rat offsprings were chronically treated with bifidobacteria or citalopram and subjected to the forced swim test (FST) to assess motivational state. Cytokine concentrations in stimulated whole blood samples, monoamine levels in the brain, and central and peripheral hypothalamic-pituitary-adrenal (HPA) axis measures were also analysed. MS reduced swim behavior and increased immobility in the FST, decreased noradrenaline (NA) content in the brain, and enhanced peripheral interleukin (IL)-6 release and amygdala corticotrophin-releasing factor mRNA levels. Probiotic treatment resulted in normalization of the immune response, reversal of behavioral deficits, and restoration of basal NA concentrations in the brainstem. These findings point to a more influential role for bifidobacteria in neural function, and suggest that probiotics may have broader therapeutic applications than previously considered.
Article
Clinical and preclinical studies have associated gastrointestinal inflammation and infection with altered behavior. We investigated whether chronic gut inflammation alters behavior and brain biochemistry and examined underlying mechanisms. AKR mice were infected with the noninvasive parasite Trichuris muris and given etanercept, budesonide, or specific probiotics. Subdiaphragmatic vagotomy was performed in a subgroup of mice before infection. Gastrointestinal inflammation was assessed by histology and quantification of myeloperoxidase activity. Serum proteins were measured by proteomic analysis, circulating cytokines were measured by fluorescence activated cell sorting array, and serum tryptophan and kynurenine were measured by liquid chromatography. Behavior was assessed using light/dark preference and step-down tests. In situ hybridization was used to assess brain-derived neurotrophic factor (BDNF) expression in the brain. T muris caused mild to moderate colonic inflammation and anxiety-like behavior that was associated with decreased hippocampal BDNF messenger RNA (mRNA). Circulating tumor necrosis factor-α and interferon-γ, as well as the kynurenine and kynurenine/tryptophan ratio, were increased. Proteomic analysis showed altered levels of several proteins related to inflammation and neural function. Administration of etanercept, and to a lesser degree of budesonide, normalized behavior, reduced cytokine and kynurenine levels, but did not influence BDNF expression. The probiotic Bifidobacterium longum normalized behavior and BDNF mRNA but did not affect cytokine or kynurenine levels. Anxiety-like behavior was present in infected mice after vagotomy. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry, which can be normalized by inflammation-dependent and -independent mechanisms, neither of which requires the integrity of the vagus nerve.
Article
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.
Article
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.
Article
Gut microflora-mucosal interactions may be involved in the pathogenesis of irritable bowel syndrome (IBS). To investigate the efficacy of a novel prebiotic trans-galactooligosaccharide in changing the colonic microflora and improve the symptoms in IBS sufferers. In all, 44 patients with Rome II positive IBS completed a 12-week single centre parallel crossover controlled clinical trial. Patients were randomized to receive either 3.5 g/d prebiotic, 7 g/d prebiotic or 7 g/d placebo. IBS symptoms were monitored weekly and scored according to a 7-point Likert scale. Changes in faecal microflora, stool frequency and form (Bristol stool scale) subjective global assessment (SGA), anxiety and depression and QOL scores were also monitored. The prebiotic significantly enhanced faecal bifidobacteria (3.5 g/d P < 0.005; 7 g/d P < 0.001). Placebo was without effect on the clinical parameters monitored, while the prebiotic at 3.5 g/d significantly changed stool consistency (P < 0.05), improved flatulence (P < 0.05) bloating (P < 0.05), composite score of symptoms (P < 0.05) and SGA (P < 0.05). The prebiotic at 7 g/d significantly improved SGA (P < 0.05) and anxiety scores (P < 0.05). The galactooligosaccharide acted as a prebiotic in specifically stimulating gut bifidobacteria in IBS patients and is effective in alleviating symptoms. These findings suggest that the prebiotic has potential as a therapeutic agent in IBS.
Article
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.
Article
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.
Article
Data suggest that subjects with irritable bowel syndrome are more likely to report a recent course of antibiotics. This study tests the hypothesis that a course of antibiotics is a risk factor for an increase in the number of functional bowel complaints over a 4-month period in a general population sample. We initiated a prospective case-control study in three general practices in South London. Consecutive patients aged 16-49 attending their general practitioner with non-GI complaints and given a prescription for antibiotics were invited to participate. Comparison subjects who had not had antibiotics for 1 yr were identified from the practice records by age group, gender, and previous general practitioner visits. Fifty-eight antibiotic and 65 control patients agreed to participate. Questionnaires covering demographic, GI, and psychological data were sent at recruitment and at 4 months. Seventy-four percent of subjects completed the study. The number of symptoms at follow-up compared to that at recruitment. Twenty of 42 antibiotic subjects (48%) versus 11/49 control subjects (22%) demonstrated one or more additional functional bowel symptoms at 4 months (unadjusted odds ratio = 3.14 [1.27-7.75]) (chi2 = 6.4, p = 0.01). Ten of 42 antibiotic subjects (24%) versus 3/49 control subjects (6%) demonstrated two or more additional functional bowel symptoms at 4 months (unadjusted odds ratio = 4.79 [1.22-18.80]) (chi2 = 5.8, p = 0.02). Functional bowel symptoms come and go, but subjects who are given a course of antibiotics are more than three times as likely to report more bowel symptoms 4 months later than controls.