Depression is a long-term, related to stress neuropsychiatric disorder, leading to psychological health issues including worthlessness, anhedonia, sleep and appetite disturbances, dysregulated HPA axis, neuronal cell death, and alterations in the gut microbiota (GM). Dysregulated HPA axis increases level of glucocorticoids that induce proinflammatory response with activation of abnormal kynurenine pathway via metabolizing indoleamine-2,3-dioxygenase (IDO). Kynurenine pathway leads to excitotoxicity of N-methyl-D-aspartate (NMDA) receptor responsible for neuronal cell death. Further, probiotics supplementation gained attention from researchers and clinicians to treat neuropsychiatric diseases. GM alteration remains a key reason for depression; however, there is limited information about the role of probiotics on depression involving glucocorticoid receptor and NMDA excitotoxicity through IDO. Chronic unpredictable mild stress (CUMS) model was prepared to check the role of Lactobacillus fermentum ATCC 9338 (LF) and 1-methyl-D-tryptophan (1-MT) in depression. Herein, mice were placed into experimental groups: control, CUMS stressed, CUMS vehicle, CUMS LF, CUMS 1-MT, and CUMS UT (untreated). Results showed that peroral administration of 1 × 108 CFU/day/mouse LF and intraperitoneal dose of 1-MT (15 mg/kg BW/day) alleviate depressive-like behavior and improve motor coordination and walking patterns. Mice supplemented with LF and 1-MT exhibited a decreased expression of GR and NMDAR2b in the cortex, hippocampus, and medulla. Acetylcholinesterase, SOD, and CAT activities were improved in CUMS mice with supplementation of LF and 1-MT. The GM abundance in LF mice was similar to that in control mice. Such study suggests the roles of LF and 1-MT in depression and oxidative stress, and helpful to understand their therapeutic potential through the HPA axis and IDO.

Major Depressive Disorder (MDD) is a prevalent psychiatric disorder with a profound impact on global health, necessitating a deeper understanding of its pathophysiology. This review synthesizes current evidence linking neurogenesis, particularly in the hippocampal region, with MDD. Accumulating data showed a significant reduction of neurogenesis in the hippocampal region of both MDD patients and various MDD rodent models. We highlight the role of brain-derived neurotrophic factor (BDNF) and its associated signaling pathways in regulating neurogenesis and depressive symptoms. Additionally, the influence of gut microbiota on the neurogenesis in depression is presented, offering a novel perspective on environmental modulation of neurogenesis. This review also underscores the potential antidepressant interventions targeting neurogenesis and BDNF's regulation, such as therapeutic benefits of environmental enrichment, physical activity, and pharmacological agents in enhancing neurogenesis and alleviating depressive symptoms. Together, this systemic review provides a foundation for future research aiming at developing personalized treatments by targeting neurogenesis in MDD, potentially leading to novel biomarkers and therapeutic strategies.

Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric impairments caused by Huntingtin (HTT) gene mutations, resulting in the mutant huntingtin (mHTT) protein. Both innate and adaptive immunities play crucial roles in the pathogenesis of HD. In this chapter, we explore the vital role of the gut microbiota in HD, emphasizing its impact on the immune response and brain health via the gut-brain axis. Dysbiosis influences immune responses and HD pathogenesis through microbial metabolites such as short-chain fatty acids (SCFAs) and pathogen-associated molecular patterns (PAMPs). We discuss advanced mathematical models, telemedicine, and biosensors for tracking HD progression and detecting gut dysbiosis. Nutritional interventions to restore microbiota balance and using artificial intelligence and machine learning to predict disease prognosis and personalized treatments have been highlighted. Based on their unique immune profiles and gut microbiota, personalized medicine has been proposed as a promising strategy for effective HD treatment.

Chronic stress is a widespread problem that significantly affects both physical and mental health, leading to numerous complications such as mood disorders, cognitive impairments, gastrointestinal issues, and chronic diseases. The dysregulation of the hypothalamic pituitary adrenal (HPA) axis and the gut-brain axis underlies several stress related disorders, leading to systemic inflammation, neuroinflammation, dysbiosis, and impaired gut barrier integrity. This review emphasizes the growing significance of probiotics as a potential treatment strategy for addressing chronic stress. Probiotics are living bacteria that provide health benefits when consumed in sufficient quantities, acting via several processes including restoration of gut microbial composition, augmentation of gut barrier integrity, and synthesis bioactive compounds such as neurotransmitters and short-chain fatty acids. These effects lead to reduced systemic and neuroinflammation, enhanced neuroplasticity, and the regulation of stress responsive pathways, including the HPA axis. Moreover, probiotics enhance parasympathetic nervous system activity by modulating vagus signaling. Current review indicates the promise of probiotics in alleviating chronic stress; nonetheless, substantial gaps exist regarding strain specific benefits, appropriate doses, and long-term safety. It is essential to address these constraints by comprehensive, large scale clinical studies and tailored therapies. This review highlights the significance of probiotics as a natural, non-invasive approach to chronic stress management, providing an innovative solution for the worldwide issue of stress related health problems.

Probiotics may improve mood, but their role as adjunctive therapy for major depressive disorder (MDD) is not well understood. This study examines the effects of probiotics on depression severity, brain-derived neurotrophic factor (BDNF), adrenocorticotropic hormone (ACTH), and cortisol levels in MDD patients. Fifty medication-free MDD patients were randomized to receive probiotics with fluoxetine (n = 25) or placebo with fluoxetine (n = 25) for 8 weeks. Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS-24), and fasting blood samples were collected at baseline and study conclusion. Forty-four patients completed the trial. The probiotic group showed a significant reduction in depression severity compared with the placebo group (p = 0.001). No significant differences were observed in serum cortisol (p = 0.46) and ACTH levels (p = 0.44). Plasma BDNF levels increased slightly in the probiotic group but were not statistically significant. Probiotic supplementation with fluoxetine significantly reduces depression severity in MDD patients.

The microbiota-gut-brain-axis (MGBA) plays a role in the aetiology of mental disorders. Depression, a leading cause of disability worldwide, may be improved by probiotics. The aim of this narrative review is to investigate and synthesize the current evidence linking probiotic food supplementation with depressive symptomology.

The gut and the brain communicate and interact via the MGBA through inflammation and the immune system, short chain fatty acid production, neuronal innervation and activation as well as endocrine and neurotransmitter modulation. Dysregulation of gut-brain pathways are caused by gut dysbiosis and implicated in the onset, persistence and exacerbation of depression related symptoms. Modulation of the gut microbiota via administration of probiotics has shown to reduce depressive symptom severity with Bifidobacterium and Lactobacillus strains being the most reported. Probiotics may produce greater benefits in mild depression rather than in chronic, treatment resistant depression. Probiotic supplementation is a promising and safe approach for the prevention of severe depressive disorders in high-risk individuals such as people with subthreshold depression. However, the mechanistic pathways of the MGBA require further investigation and additional human clinical trials are necessary to evaluate the role of probiotics on depression.

Cerebral ischemia/reperfusion (I/R) injury is an important pathophysiological condition of ischemic stroke that involves a variety of physiological and pathological cell death pathways, including autophagy, apoptosis, necroptosis, and phagoptosis, among which autophagy is the most studied. We have reviewed studies published in the past 5 years regarding the association between autophagy and cerebral I/R injury. To the best of our knowledge, this is the first review article summarizing potential candidates targeting autophagic pathways in the treatment of I/R injury post ischemic stroke. The findings of this review may help to better understand the pathogenesis and mechanisms of I/R events and bridge the gap between basic and translational research that may lead to the development of novel therapeutic approaches for I/R injury.

Adult neural stem cells divide to produce neurons that migrate to preexisting neuronal circuits in a process named adult neurogenesis. Adult neurogenesis is one of the most exciting areas of current neuroscience, and it may be involved in a range of brain functions, including cognition, learning, memory, and social and behavior changes. While there is a growing number of multi-omics studies on adult neurogenesis, generalized analyses from a multi-omics perspective are lacking. In this review, we summarize studies related to genomics, metabolomics, proteomics, epigenomics, transcriptomics, and microbiomics of adult neurogenesis, and then discuss their future research priorities and potential neighborhoods. This will provide theoretical guidance and new directions for future research on adult neurogenesis.

The microbiota-gut-brain axis (MGBA) plays a significant role in the maintenance of brain structure and function. The MGBA serves as a conduit between the CNS and the ENS, facilitating communication between the emotional and cognitive centers of the brain via diverse pathways. In the initial stages of this review, we will examine the way how MGBA affects neurogenesis, neuronal dendritic morphology, axonal myelination, microglia structure, brain blood barrier (BBB) structure and permeability, and synaptic structure. Furthermore, we will review the potential mechanistic pathways of neuroplasticity through MGBA influence. The short-chain fatty acids (SCFAs) play a pivotal role in the MGBA, where they can modify the BBB. We will therefore discuss how SCFAs can influence microglia, neuronal, and astrocyte function, as well as their role in brain disorders such as Alzheimer's disease (AD), and Parkinson's disease (PD). Subsequently, we will examine the technical strategies employed to study MGBA interactions, including using germ-free (GF) animals, probiotics, fecal microbiota transplantation (FMT), and antibiotics-induced dysbiosis. Finally, we will examine how particular bacterial strains can affect brain structure and function. By gaining a deeper understanding of the MGBA, it may be possible to facilitate research into microbial-based pharmacological interventions and therapeutic strategies for neurological diseases.

It has been shown that the microflora of the gastrointestinal tract undergoes changes in obese individuals. The present study aimed to investigate the effect of kefir fortified with two strains, Lactobacillus helveticus and Bifidobacterium longum, on depression, appetite, oxidative stress, and inflammatory parameters in overweight and obese elderly individuals.

This study was a double-blind, randomized, and placebo-controlled clinical trial conducted on 67 elderly men aged over 65, who were randomly divided into two groups. One group (n = 35) received one bottle (240 cc) of regular kefir as a placebo, while the intervention group (n = 32) received one bottle of probiotic-fortified kefir for eight weeks. Depression and appetite were evaluated using the Geriatric Depression Scale-15 (GDS-15) and a validated Visual Analogue Scale (VAS), respectively. Oxidative stress parameters were assessed using the standard calorimetric method, and inflammatory parameters were measured via the enzyme-linked immunosorbent assay method (ELISA). The differences between the two groups were compared using the independent samples T-test.

The median age of participant in both groups was 65 years. A significant difference in depression scores and the mean change between the two groups was observed after eight weeks (p = 0.001 and p = 0.042, respectively). Within-group comparison revealed a significant increase in appetite scores in both groups (p < 0.05 for both). Moreover, a significant difference in the changes in total antioxidant capacity (TAC) was noted (p = 0.009). However, no significant differences were observed in other oxidative and inflammatory parameters between the two groups (p˃0.05 for all).

The results demonstrated the positive impact of two specific strains of Bifidobacterium and Lactobacillus on improving depression in the elderly. However, when comparing the two groups, no significant effects were observed on appetite, inflammation, and oxidative stress parameters, except for TAC.

Increasing interest in probiotics for mental health has led to products marketed to consumers claiming psychological benefits. This study aimed to identify mental health claims on probiotic supplements and to provide a narrative review of the scientific evidence to support these claims.

Probiotic supplements with mental health claims on the product label were identified. A search of the scientific literature was performed using Google Scholar, PubMed and Cochrane Central Register of Controlled Trials. Studies were included if the primary outcome was mental health or a biomarker of mental health, if they investigated the exact probiotic strain or combination of strains as present in the product, and if the study was a trial of probiotics conducted in either humans or animals. Included studies were assessed for risk of bias.

Fourteen probiotic products with mental health claims were identified containing five different strains or strain combinations. Eighteen studies relevant to the products and investigating mental health outcomes met inclusion criteria. Ten studies investigated the same combination of probiotics and provided evidence to support the claims made. Statistically significant results were not universally present for all products.

The amount and quality of evidence to support claims of mental health benefits made on probiotic products is variable. The results support the need for a grading system to facilitate informed consumer decision-making when choosing a probiotic supplement to support mental health.

The gut microbiota plays a key role in the brain function impairment caused by chronic stress, yet its exact mechanism remains unclear. Many studies have revealed the important role of miR-124 in the central nervous system. Meanwhile, previous studies have indicated that miR-124 may be regulated by chronic stress and gut microbiota. Here, we aimed to explore whether miR-124 serves as a mediator for the impacts of gut microbial dysbiosis on brain function in mice subjected to chronic stress. Repeated daily restraint stress for 4 weeks was used to induce chronic stress in mice. Chronic stress resulted in gut microbial dysbiosis, abnormal behaviors, and a decrease in hippocampal miR-124 levels. Treatment with different probiotic mixtures significantly alleviated the effects of chronic stress on hippocampal miR-124 levels and mouse behaviors. Suppression of hippocampal miR-124 expression reversed the beneficial effects of probiotics on cognitive function, neurogenesis, and related molecular markers in chronically stressed mice. Bioinformatics analysis and qPCR suggested that Ptpn11 might be a target gene for miR-124 in mediating the effects of gut microbial dysbiosis on brain function in these mice. These findings suggest that miR-124 is a pivotal regulator that mediates the detrimental effects of gut microbial dysbiosis on brain function and the subsequent cognitive impairment during chronic stress.

The microbiota-gut-brain axis is a pivotal medium of crosstalk between the central nervous system (CNS) and the gastrointestinal tract. It is an intricate network of synergistic molecular pathways that exert their effects far beyond their local vicinity and even affect the systemic functioning of the body. The current review explores the involvement of the gut-brain axis (GBA) in the functioning of the nervous system, with a special emphasis on the neurodegeneration, cognitive decline, and neuroinflammation that occur in Alzheimer's disease (AD) and Parkinson's disease (PD). Gut-derived microbial metabolites play an important role in facilitating this interaction. We also highlighted the complex interaction between gut-derived metabolites and CNS processes, demonstrating how microbial dysbiosis might result in clinical disorders. Short-chain fatty acids have neuroprotective properties, whereas branched-chain amino acids, trimethylamine-N-oxide (TMAO), and tryptophan derivatives such as indole have negative effects at high concentrations. Furthermore, we cover pharmaceutical and nonpharmacological approaches for restoring the gut microbial balance and promoting neurological health. We further expanded on nutritional therapies and lifestyle changes, such as the Mediterranean diet and exercise. Next, we focused on food-controlling habits such as caloric restriction and intermittent fasting. Moreover, interventional techniques such as prebiotics, probiotics, and pharmacological medications have also been utilized to modify the GBA. Historical microbiome research from early discoveries to recent studies linking gut health to cognitive and emotional well-being has increased our understanding of the GBA.

Traumatic brain injury (TBI) represents a multifaceted pathological condition resulting from external forces that disrupt neuronal integrity and function. This narrative review explores the intricate relationship between dietary macronutrients, gut microbiota (GM), and neuroinflammation in the TBI. We delineate the dual aspects of TBI: the immediate mechanical damage (primary injury) and the subsequent biological processes (secondary injury) that exacerbate neuronal damage. Dysregulation of the gut-brain axis emerges as a critical factor in the neuroinflammatory response, emphasizing the role of the GM in mediating immune responses. Recent evidence indicates that specific macronutrients, including lipids, proteins, and probiotics, can influence microbiota composition and in turn modulate neuroinflammation. Moreover, specialized dietary interventions may promote resilience against secondary insults and support neurological recovery post-TBI. This review aims to synthesize the current preclinical and clinical evidence on the potential of dietary strategies in mitigating neuroinflammatory pathways, suggesting that targeted nutrition and gut health optimization could serve as promising therapeutic modalities in TBI management.

This study aimed to ascertain the potential benefits of green radish polysaccharide (GRP) in treating alcoholic liver disease (ALD) in mice and explore its mechanism of action. Using biochemical analysis, high-throughput sequencing of gut microbiota, and gas chromatography-mass spectrometry to measure short-chain fatty acids (SCFAs) in feces, we found that GRP intervention significantly improved lipid metabolism and hepatic function in mice subjected to excessive alcohol intake. The GRP intervention reduced malondialdehyde levels by 66% and increased total superoxide dismutase levels by 22%, thereby mitigating alcohol-induced oxidative stress. Furthermore, GRP intervention in mice with alcohol consumption resulted in a reduction in tumor necrosis factor, interleukin 6, and lipopolysaccharide levels by 12%, 9%, and 25%, respectively, effectively attenuating alcoholic liver inflammation. 16S rRNA amplicon sequencing demonstrated that excessive alcohol consumption markedly altered the gut microbiota composition in mice. The GRP treatment resulted in a significant reduction in the number of beneficial bacteria (Lactobacillus and Lachnospiraceae_NK4A136_group) and an increase in the proportion of harmful bacteria (Muribaculaceae and Verrucomicrobiota). The metabolomic analyses of the SCFAs demonstrated an increase in the contents of SCFAs, acetic acid, propionic acid, and butyric acid, following GRP supplementation. Furthermore, the metabolic levels of cholinergic synapses and glycolysis/gluconeogenesis were found to be modulated. In conclusion, these findings suggest that GRP may attenuate alcohol-induced oxidative damage in the liver by modulating the gut microbiota and hepatic metabolic pathways. This may position GRP as a potential functional component for ALD prevention.

The relationship between the mind, gut, and sleep is not static and requires proper harmony for optimal emotional health. Recent evidence suggests that gut health is a key player in regulating mental and physical health via bidirectional communication between the brain and gut.

A cross-sectional comparative study was undertaken on 200 participants aged 25-40 years old for two months at a tertiary care hospital. A community-based method was used to select the participants from in and around Pune. The survey was conducted online with the help of a self-designed well-structured detailed questionnaire that included a demographic profile, medical history, history of sleep pattern, gut health status, emotional well-being status about gut and sleep physiology, and lifestyle-related issues and problems was administered to all the study participants.

A statistically significant correlation was observed between the duration of sleep; and gastrointestinal (GI) symptoms including heartburn (P=0.03) constipation (P=0.03), bloating (P=0.04), and indigestion (P=0.051). Specific GI symptoms as mentioned above were found to affect the study participants' emotional well-being significantly. Regular physical exercise demonstrated a significant correlation with an increased duration of sleep (P=0.003). Consumption of tobacco, alcohol; smoking, and consumption of stimulants like tea, coffee, and coke showed a significant effect on both the duration and quality of sleep (P=0.004). Gut and sleep disturbances were more common in north Indian subjects as compared to south Indian subjects (P=0.003). The upper socioeconomic population had more GI; sleep and emotional disturbances as compared to the lower socioeconomic study subjects (P=0.002).

The relationship between sleep patterns, emotional well-being gut health is bidirectional. Prioritizing good sleep hygiene, managing stress through mindfulness or relaxation techniques, and maintaining a balanced diet that supports gut health are crucial steps in promoting overall well-being.

The microbial-gut-brain axis has received much attention in recent years, and regulating intestinal flora can effectively improve sleep disorders, which hints the potential effects of probiotics on sleep disorders, but lack of research evidence for meta-analysis. Therefore, this study aims to quantitatively evaluate the influence of probiotics on sleep disorders and sub-healthy sleep conditions.

Up to 2023, online databases including Pubmed, Embase, Cochrane library, Web of science have been searched for studies involving adults who consume probiotics or paraprobiotics in controlled trials, during which, changes in subjective and/or objective sleep parameters and contributing factors in sleeping quality are examined. We conduct a meta-analysis of 11 clinical randomized controlled studies.

Probiotic supplementation improves sleep states to some extent in adults with sleep disorders and healthy adults with condition-induced sleep disorders (-0.34 [-0.56 to -0.13]; I 2 = 42.6%; p = 0.001). Meanwhile, subgroup analysis shows that the effect of probiotics on improving sleep disorders is influenced by other factors such as the health states of the subjects, the duration of the intervention, the type of strain, and the test criteria.

Probiotics and paraprobiotics have a significant positive effect on the sleep quality of adults with sleep disorders or sub-healthy sleep conditions. However, the therapeutic effects of probiotics on sleep problems need future additional trials.

https://inplasy.com/inplasy-2022-12-0066/, identifier 2022120066.

This review explores the critical role of the human microbiome in neurological and neurodegenerative disorders, focusing on gut-brain axis dysfunction caused by dysbiosis, an imbalance in gut bacteria. Dysbiosis has been linked to diseases such as Alzheimer's disease, Parkinson's disease (PD), multiple sclerosis (MS), and stroke. The gut microbiome influences the central nervous system (CNS) through signaling molecules, including short-chain fatty acids, neurotransmitters, and metabolites, impacting brain health and disease progression. Emerging therapies, such as fecal microbiota transplantation (FMT), have shown promise in restoring microbial balance and alleviating neurological symptoms, especially in Alzheimer's and PD. Additionally, nutritional interventions such as probiotics, prebiotics, and specialized diets are being investigated for their ability to modify gut microbiota and improve patient outcomes. This review highlights the therapeutic potential of gut microbiota modulation but emphasizes the need for further clinical trials to establish the safety and efficacy of these interventions in neurological and mental health disorders.

The intricate interplay existing between gut microbiota and homeostasis extends to the realm of the brain, where emerging research underscores the significant impact of the microbiota on mood regulation and overall neurological well-being and vice-versa, with inflammation playing a pivotal role in mediating these complex interactions. This comprehensive review explores the complex interplay between inflammation, alterations in gut microbiota, and their impact on major depressive disorder (MDD). It provides a cohesive framework for the puzzle pieces of this triad, emphasizing recent advancements in understanding the gut microbiota and inflammatory states' contribution to the depressive features. Two directions of communication between the gut and the brain in depression are discussed, with inflammation serving as a potential modulator. Therapeutic implications were discussed as well, drawing insights from interventional studies on the effects of probiotics on gut bacterial composition and depressive symptoms. Ultimately, this review will attempt to provide a complete and valuable framework for future research and therapeutic interventions in MDD.

Post-stroke depression (PSD) is a psychological disease that can occur following a stroke and is associated with serious consequences. Research on the pathogenesis and treatment of PSD is still in the infancy stage. Patients with PSD often exhibit gastrointestinal symptoms; therefore the role of gut microbiota in the pathophysiology and potential treatment effects of PSD has become a hot topic of research. In this review, describe the research on the pathogenesis and therapy of PSD. We also describe how the gut microbiota influences neurotransmitters, the endocrine system, energy metabolism, and the immune system. It was proposed that the gut microbiota is involved in the pathogenesis and treatment of PSD through the regulation of neurotransmitter levels, vagal signaling, hypothalamic-pituitary-adrenal axis activation and inhibition, hormone secretion and release, in addition to immunity and inflammation.

Nutraceuticals have been described as phytocomplexes when derived from foods of plant origin or a pool of secondary metabolites when derived from foods of animal origin, which are concentrated and administered in an appropriate form and can promote beneficial health effects in the prevention/treatment of diseases. Considering that pharmaceutical medications can cause side effects, there is a growing interest in using nutraceuticals as an adjuvant therapeutic tool for several disorders involving autonomic dysfunction, such as obesity, atherosclerosis and other cardiometabolic diseases. This review summarizes and discusses the evidence from the literature on the effects of various nutraceuticals on autonomic control, addressing the gut microbiota modulation, production of secondary metabolites from bioactive compounds, and improvement of physical and chemical properties of cell membranes. Additionally, the safety of nutraceuticals and prospects are discussed. Probiotics, resveratrol, quercetin, curcumin, nitrate, inositol, L-carnosine, and n-3 polyunsaturated fatty acids (n-3 PUFAs) are among the nutraceuticals most studied to improve autonomic dysfunction in experimental animal models and clinical trials. Further human studies are needed to elucidate the effects of nutraceuticals formulated of multitarget compounds and their underlying mechanisms of action, which could benefit conditions involving autonomic dysfunction.

Constipation is affected by a number of risk variables, including cardiovascular disease and growth factors. However, the impacts of gut flora on constipation incidence has not been shown. This work, Single-Variable Mendelian Randomization (SVMR) was utilized to estimate the causal relationship between the Eubacterium genus or Rumphococcus, and constipation.

Data for constipation, Eubacterium genus and Rumphococcus were taken from the Integrated Epidemiology Unit (IEU) open GWAS database. Including 218,792 constipation samples, and there were 16,380,466 Single Nucleotide Polymorphisms (SNPs) for constipation. The ids of Eubacterium genus and Rumphococcus were sourced from MiBioGen database. The sample count for the Eubacterium genus was 17,380, with 656 SNPs. In addition, the sample size for Rumphococcus was 15,339, with 545 SNPs. The SVMR was performed to assess the risk of Eubacterium genus and Rumphococcus in constipation using weighted median, MR Egger, simple mode, inverse variance weighted (IVW), and weighted mode. Finally, we did a sensitivity analysis that included a heterogeneity, horizontal pleiotropy, and Leave-One-Out (LOO) test to examine the viability of the MR data.

The SVMR revealed that the Eubacterium genus and Rumphococcus were causally connected to constipation, with Rumphococcus (P = 0.042, OR = 1.074) as a hazardous factor and Eubacterium genus (P = 0.004, OR = 0.909) as a safety factor. Sensitivity tests then revealed the absence of variability between the constipation and the exposure factors (Eubacterium genus and Rumphococcus). Additionally, there were no other confounding factors and the examined SNPs could only influence constipation through the aforementioned exposure factors, respectively. As a result, the MR results were fairly robust.

Our investigation verified the causal links between the Eubacterium genus or Rumphococcus, and constipation, with greater Rumphococcus expression increasing the likelihood of constipation and the opposite being true for the Eubacterium genus.

Multiple sclerosis (MS) is a neurological autoimmune disorder predominantly afflicting young adults. The etiology of MS is intricate, involving a variety of environmental and genetic factors. Current research increasingly focuses on the substantial contribution of gut microbiota in MS pathogenesis. The commensal microbiota resident within the intestinal milieu assumes a central role within the intricate network recognized as the gut-brain axis (GBA), wielding beneficial impact in neurological and psychological facets. As a result, the modulation of gut microbiota is considered a pivotal aspect in the management of neural disorders, including MS. Recent investigations have unveiled the possibility of using probiotic supplements as a promising strategy for exerting a positive impact on the course of MS. This therapeutic approach operates through several mechanisms, including the reinforcement of gut epithelial integrity, augmentation of the host's resistance against pathogenic microorganisms, and facilitation of mucosal immunomodulatory processes. The present study comprehensively explains the gut microbiome's profound influence on the central nervous system (CNS). It underscores the pivotal role played by probiotics in forming the immune system and modulating neurotransmitter function. Furthermore, the investigation elucidates various instances of probiotic utilization in MS patients, shedding light on the potential therapeutic advantages afforded by this intervention.

Radiotherapy is a widely used cancer treatment that utilizes powerful radiation to destroy cancer cells and shrink tumors. While radiation can be beneficial, it can also harm the healthy tissues surrounding the tumor. Recent research indicates that the microbiota, the collection of microorganisms in our body, may play a role in influencing the effectiveness and side effects of radiation therapy. Studies have shown that specific species of bacteria living in the stomach can influence the immune system's response to radiation, potentially increasing the effectiveness of treatment. Additionally, the microbiota may contribute to adverse effects like radiation-induced diarrhea. A potential strategy to enhance radiotherapy outcomes and capitalize on the microbiome involves using probiotics. Probiotics are living microorganisms that offer health benefits when consumed in sufficient quantities. Several studies have indicated that probiotics have the potential to alter the composition of the gut microbiota, resulting in an enhanced immune response to radiation therapy and consequently improving the efficacy of the treatment. It is important to note that radiation can disrupt the natural balance of gut bacteria, resulting in increased intestinal permeability and inflammatory conditions. These disruptions can lead to adverse effects such as diarrhea and damage to the intestinal lining. The emerging field of radiotherapy microbiome research offers a promising avenue for optimizing cancer treatment outcomes. This paper aims to provide an overview of the human microbiome and its role in augmenting radiation effectiveness while minimizing damage.

The gut-brain axis (GBA) plays a dominant role in maintaining homeostasis as well as contributes to mental health maintenance. The pathways that underpin the axis expand from macroscopic interactions with the nervous system, to the molecular signals that include microbial metabolites, tight junction protein expression, or cytokines released during inflammation. The dysfunctional GBA has been repeatedly linked to the occurrence of anxiety- and depressive-like behaviors development. The importance of the inflammatory aspects of the altered GBA has recently been highlighted in the literature. Here we summarize current reports on GBA signaling which involves the immune response within the intestinal and blood-brain barrier (BBB). We also emphasize the effect of stress response on altering barriers' permeability, and the therapeutic potential of microbiota restoration by probiotic administration or microbiota transplantation, based on the latest animal studies. Most research performed on various stress models showed an association between anxiety- and depressive-like behaviors, dysbiosis of gut microbiota, and disruption of intestinal permeability with simultaneous changes in BBB integrity. It could be postulated that under stress conditions impaired communication across BBB may therefore represent a significant mechanism allowing the gut microbiota to affect brain functions.

The microbiota-gut-brain axis (MGBA) represents a sophisticated communication network between the brain and the gut, involving immunological, endocrinological, and neural mediators. This bidirectional interaction is facilitated through the vagus nerve, sympathetic and parasympathetic fibers, and is regulated by the hypothalamic-pituitary-adrenal (HPA) axis. Evidence shows that alterations in gut microbiota composition, or dysbiosis, significantly impact neurological disorders (NDs) like anxiety, depression, autism, Parkinson's disease (PD), and Alzheimer's disease (AD). Dysbiosis can affect the central nervous system (CNS) via neuroinflammation and microglial activation, highlighting the importance of the microbiota-gut-brain axis (MGBA) in disease pathogenesis. The microbiota influences the immune system by modulating chemokines and cytokines, impacting neuronal health. Synbiotics have shown promise in treating NDs by enhancing cognitive function and reducing inflammation. The gut microbiota's role in producing neurotransmitters and neuroactive compounds, such as short-chain fatty acids (SCFAs), is critical for CNS homeostasis. Therapeutic interventions targeting the MGBA, including dietary modulation and synbiotic supplementation, offer potential benefits for managing neurodegenerative disorders. However, more in-depth clinical studies are necessary to fully understand and harness the therapeutic potential of the MGBA in neurological health and disease.

Dasatinib and quercetin (D & Q) have demonstrated promise in improving aged-related pathophysiological dysfunctions in humans and mice. Herein we aimed to ascertain whether the heat stress (HS)-induced cognitive deficits in aged or even young adult male mice can be reduced by D & Q therapy.

Before the onset of HS, animals were pre-treated with D & Q or placebo for 3 consecutive days every 2 weeks over a 10-week period. Cognitive function, intestinal barrier permeability, and blood-brain barrier permeability were assessed.

Compared to the non-HS young adult male mice, the HS young adult male mice or the aged male mice had significantly lesser extents of the exacerbated stress reactions, intestinal barrier disruption, endotoxemia, systemic inflammation and oxidative stress, blood-brain barrier disruption, hippocampal inflammation and oxidative stress, and cognitive deficits evaluated at 7 days post-HS. All the cognitive deficits and other syndromes that occurred in young adult HS mice or in aged HS mice were significantly attenuated by D & Q therapy (P < 0.01). Compared to the young adult HS mice, the aged HS mice had significantly (P < 0.01) higher severity of cognitive deficits and other related syndromes.

First, our data show that aged male mice are more vulnerable to HS-induced cognitive deficits than those of the young adult male mice. Second, we demonstrate that a combination of D and Q therapy attenuates cognitive deficits in heat stressed aged or young adult male mice via broad normalization of the brain-gut-endotoxin axis function.

Thrombomodulin (TM) exerts anticoagulant and anti-inflammatory effects to improve the survival of patients with septic shock. Heat stroke resembles septic shock in many aspects. We tested whether TM would improve cognitive deficits and related causative factors in heat-stressed (HS) mice.

Adult male mice were exposed to HS (33°C for 2 hours daily for 7 consecutive days) to induce cognitive deficits. Recombinant human soluble TM (1 mg/kg, i.p.) was administered immediately after the first HS trial and then once daily for 7 consecutive days. We performed the Y-maze, novel objective recognition, and passive avoidance tests to evaluate cognitive function. Plasma levels of lipopolysaccharide (LPS), high-mobility group box 1 (HMGB1), coagulation parameters, and both plasma and tissue levels of inflammatory and oxidative stress markers were biochemically measured. The duodenum and hippocampus sections were immunohistochemically stained. The intestinal and blood-brain barrier permeability were determined.

Compared with controls, HS mice treated with TM had lesser extents of cognitive deficits, exacerbated stress reactions, gut barrier disruption, endotoxemia, blood-brain barrier disruption, and inflammatory, oxidative, and coagulatory injury to heart, duodenum, and hippocampal tissues, and increased plasma HMGB1. In addition to reducing cognitive deficits, TM therapy alleviated all the abovementioned complications in heat-stressed mice.

The findings suggest that HS can lead to exacerbated stress reactions, endotoxemia, gut barrier disruption, blood-brain barrier disruption, hippocampal inflammation, coagulopathy, and oxidative stress, which may act as causative factors for cognitive deficits. TM, an anti-inflammatory, antioxidant, and anti-coagulatory agent, inhibited heat stress-induced cognitive deficits in mice.

Ageing is inevitable and poses a universal challenge for all living organisms, including humans. The human body experiences rapid cell division and metabolism until approximately 25 years of age, after which the accumulation of metabolic by-products and cellular damage leads to age-related diseases. Neurodegenerative diseases are of concern due to their irreversible nature, lack of effective treatment, and impact on society and the economy. Researchers are interested in finding drugs that can effectively alleviate ageing and age-related diseases without side-effects. Psychobiotics are a novel class of probiotic organisms and prebiotic interventions that confer mental health benefits to the host when taken appropriately. Psychobiotic strains affect functions related to the central nervous system (CNS) and behaviors mediated by the Gut-Brain-Axis (GBA) through various pathways. There is an increasing interest in researchers of these microbial-based psychopharmaceuticals. Psychobiotics have been reported to reduce neuronal ageing, inflammation, oxidative stress, and cortisol levels; increase synaptic plasticity and levels of neurotransmitters and antioxidants. The present review focuses on the manifestation of elderly neurodegenerative and mental disorders, particularly Alzheimer's disease (AD), Parkinson's disease (PD), and depression, and the current status of their potential alleviation through psychobiotic interventions, highlighting their possible mechanisms of action.

Accumulating data show that probiotics may be beneficial for reducing depressive, anxiety, and stress symptoms. However, the best combinations and species of probiotics have not been identified. The objective of our study was to assess the most effective combinations and components of different probiotics through network meta-analysis.

A systematic search of four databases, PubMed, Web of Science, Cochrane, and Embase, was conducted from inception to 11 January 2024. The GRADE framework was used to assess the quality of evidence contributing to each network estimate.

We deemed 45 trials eligible, these included 4053 participants and 10 types of interventions. The quality of evidence was rated as high or moderate. The NMA revealed that Bifidobacterium exhibited a greater probability of being the optimal probiotic species for improving anxiety symptoms (SMD = -0.80; 95% CI -1.49 to -0.11), followed by Lactobacillus (SMD = -0.49; 95% CI -0.85 to -0.12). In addition, for multiple strains, compared with the other interventions, Lactobacillus + Bifidobacterium (SMD = -0.41; 95% CI -0.73 to -0.10) had a positive effect on depression.

The NMA revealed that Lactobacillus and Bifidobacterium had prominent efficacy in the treatment of individuals with anxiety, depression, and combination of Lactobacillus + Bifidobacterium had a similar effect. With few direct comparisons available between probiotic species, this NMA may be instrumental in shaping the guidelines for probiotic treatment of psychological disorders.

Major depressive disorder (MDD) is a recurrent episodic mood disorder that represents the third leading cause of disability worldwide. In MDD, several factors can simultaneously contribute to its development, which complicates its diagnosis. According to practical guidelines, antidepressants are the first-line treatment for moderate to severe major depressive episodes. Traditional treatment strategies often follow a one-size-fits-all approach, resulting in suboptimal outcomes for many patients who fail to experience a response or recovery and develop the so-called "therapy-resistant depression". The high biological and clinical inter-variability within patients and the lack of robust biomarkers hinder the finding of specific therapeutic targets, contributing to the high treatment failure rates. In this frame, precision medicine, a paradigm that tailors medical interventions to individual characteristics, would help allocate the most adequate and effective treatment for each patient while minimizing its side effects. In particular, multi-omic studies may unveil the intricate interplays between genetic predispositions and exposure to environmental factors through the study of epigenomics, transcriptomics, proteomics, metabolomics, gut microbiomics, and immunomics. The integration of the flow of multi-omic information into molecular pathways may produce better outcomes than the current psychopharmacological approach, which targets singular molecular factors mainly related to the monoamine systems, disregarding the complex network of our organism. The concept of system biomedicine involves the integration and analysis of enormous datasets generated with different technologies, creating a "patient fingerprint", which defines the underlying biological mechanisms of every patient. This review, centered on precision medicine, explores the integration of multi-omic approaches as clinical tools for prediction in MDD at a single-patient level. It investigates how combining the existing technologies used for diagnostic, stratification, prognostic, and treatment-response biomarkers discovery with artificial intelligence can improve the assessment and treatment of MDD.

Over the past decade, research has reported that diet and gut health affect anxiety symptoms through changes in the gut microbiota. Therefore, the introduction of prebiotic and probiotic food favorable for the intestinal microbiota is necessary to improve the mental health of the host. The purpose of this study was to examine the contribution of prebiotic and probiotic foods to lowering anxiety symptoms using a large, nationwide population-based database.

The study population included 4,317 individuals 19 to 64 years of age who participated in the Korean National Health and Nutrition Examination Survey (KNHANES VII-3, 2019-2021). A food frequency questionnaire was used to evaluate prebiotic and probiotic food consumption. The Generalized Anxiety Disorder Assessment 7-item scale (GAD-7) assessed the severity of anxiety symptoms. The effect of prebiotic and probiotic food consumption on anxiety severity was analyzed using multiple logistic regression.

Anxiety symptom severity was significantly lower in the highest prebiotic and/or probiotic food consumption tertiles compared to the lowest food consumption tertile. We also found a sex difference in the odds ratio for anxiety symptoms. The consumption of prebiotic food was significantly associated with the highest odds of anxiety among both men and women. However, probiotic food had a significant beneficial effect on lowering anxiety symptoms in men but not in women.

Our finding suggests that prebiotic and probiotic food consumption might confer a beneficial influence on anxiety symptoms. Further research is required for a deeper understanding into the mechanisms of the positive effects of prebiotics and probiotics on anxiety.

Myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS), and long COVID are complex, multisystemic and long-term disabling conditions characterized by debilitating post-exertional malaise and other core symptoms related to immune dysregulation resultant from post-viral infection, including mitochondrial dysfunction, chronic neuroinflammation and gut dysbiosis. The reported associations between altered microbiota composition and cardinal symptoms of ME/CFS and long COVID suggest that the use of microbial preparations, such as probiotics, by restoring the homeostasis of the brain-immune-gut axis, may help in the management of symptoms in both conditions. Therefore, this review aims to investigate the implications of alerted gut microbiome and assess the evidence supporting use of microbial-based preparations, including probiotics, synbiotics, postbiotics alone and/or in combination with other nutraceuticals in the management of fatigue, inflammation and neuropsychiatric and gastrointestinal symptoms among patients with ME/CFS and long COVID.

Breast cancer survivors have an increased risk for chronic fatigue and altered gut microbiota composition, both with negative health and quality of life affects. Exercise modestly improves fatigue and is linked to gut microbial diversity and production of beneficial metabolites. Studies suggest that gut microbiota composition is a potential mechanism underlying fatigue response to exercise. Randomised controlled trials testing the effects of exercise on the gut microbiome are limited and there is a scarcity of findings specific to breast cancer survivors. The objective of this study is to determine if fitness-related modifications to gut microbiota occur and, if so, mediate the effects of aerobic exercise on fatigue response.

The research is a randomised controlled trial among breast cancer survivors aged 18-74 with fatigue. The primary aim is to determine the effects of aerobic exercise training compared with an attention control on gut microbiota composition. The secondary study aims are to test if exercise training (1) affects the gut microbiota composition directly and/or indirectly through inflammation (serum cytokines), autonomic nervous system (heart rate variability) or hypothalamic-pituitary-adrenal axis mediators (hair cortisol assays), and (2) effects on fatigue are direct and/or indirect through changes in the gut microbiota composition. All participants receive a standardised controlled diet. Assessments occur at baseline, 5 weeks, 10 weeks and 15 weeks (5 weeks post intervention completion). Faecal samples collect the gut microbiome and 16S gene sequencing will identify the microbiome. Fatigue is measured by a 13-item multidimensional fatigue scale.

The University of Alabama at Birmingham Institutional Review Board (IRB) approved this study on 15 May 2019, UAB IRB#30000320. A Data and Safety Monitoring Board convenes annually or more often if indicated. Findings will be disseminated in peer-reviewed journals and conference presentations.

ClinicalTrials.gov, NCT04088708.

In recent years, an increasing attention has given to the intricate and diverse connection of microorganisms residing in our gut and their impact on brain health and central nervous system disease. There has been a shift in mindset to understand that drug addiction is not merely a condition that affects the brain, it is now being recognized as a disorder that also involves external factors such as the intestinal microbiota, which could influence vulnerability and the development of addictive behaviors. Furthermore, stress and social interactions, which are closely linked to the intestinal microbiota, are powerful modulators of addiction. This review delves into the mechanisms through which the microbiota-stress-immune axis may shape drug addiction and social behaviors. This work integrates preclinical and clinical evidence that demonstrate the bidirectional communication between stress, social behaviors, substance use disorders and the gut microbiota, suggesting that gut microbes might modulate social stress having a significance in drug addiction.

The gut microbiota may play an important role in the development and functioning of the mammalian central nervous system. The assumption of the experiment was to prove that the use of probiotic bacterial strains in the diet of mice modifies the expression of brain proteins involved in metabolic and immunological processes.

Albino Swiss mice were administered with Bifidobacterium longum Rosell®-175 or Lactobacillus rhamnosus JB-1 every 24 h for 28 days. Protein maps were prepared from hippocampal homogenates of euthanized mice. Selected proteins that were statistically significant were purified and concentrated and identified using MALDI-TOF mass spectrometry. Among the analysed samples, 13 proteins were identified. The mean volumes of calcyon, secreted frizzled-associated protein 3, and catalase in the hippocampus of mice from both experimental groups were statistically significantly higher than in the control group. In mice supplemented with Lactobacillus rhamnosus JB-1, a lower mean volume of fragrance binding protein 2, shadow of prion protein, and glycine receptor α4 subunit was observed compared to the control.

The psychobiotics Bifidobacterium longum Rosell®-175 and Lactobacillus rhamnosus JB-1enhances expression of proteins involved in the activation and maturation of nerve cells, as well as myelination and homeostatic regulation of neurogenesis in mice. The tested psychobiotics cause a decrease in the expression of proteins associated with CNS development and in synaptic transmission, thereby reducing the capacity for communication between nerve cells. The results of the study indicate that psychobiotic bacteria can be used in auxiliary treatment of neurological disorders.

The microbiota-gut-brain (MGB) axis is a complex communication network linking the gut, microbiota, and brain, influencing various aspects of health and disease. Dysbiosis, a disturbance in the gut microbiome equilibrium, can significantly impact the MGB axis, leading to alterations in microbial composition and function. Emerging evidence highlights the connection between microbiota alterations and neurological and psychiatric disorders, including depression. This review explores the potential of psychobiotics in managing depressive disorders, emphasizing their role in restoring microbial balance and influencing the MGB axis. Psychobiotics exhibit positive effects on the intestinal barrier, immune response, cortisol levels, and the hypothalamic-pituitary-adrenal (HPA) axis. Studies suggest that probiotics may serve as an adjunct therapy for depression, especially in treatment-resistant cases. This review discusses key findings from studies on psychobiotics interventions, emphasizing their impact on the gut-brain axis and mental health. The increasing acceptance of the expanded concept of the MGB axis underscores the importance of microorganisms in mental well-being. As our understanding of the microbiome's role in health and disease grows, probiotics emerge as promising agents for addressing mental health issues, providing new avenues for therapeutic interventions in depressive disorders.

Background and Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by challenges in communication, social interactions, and repetitive behaviors. Although the factors that influence the development of this condition are unknown, certain chemical compounds such as pesticides have been proposed as possible contributors. Due to the lack of an established causal link between pesticide exposure and ASD, this study aimed to evaluate this potential association. Materials and Methods: A case-control study was carried out to ascertain the prevalence and risk associated with ASD in relation to pesticide exposure over a 21-year study period (2000-2021). Results: We included 2821 individuals diagnosed with ASD residing in areas of both high and low pesticide exposure in southern Spain. There was a rise in the ASD prevalence rate in regions with elevated pesticide use when compared to regions with low use [odds ratio (OR): 1.34, 95% confidence interval (CI), (1.24-1.44)]. Notably, men had the highest likelihood, with an OR: 1.42, 95% CI, (1.30-1.55). Furthermore, after performing multiple binary logistic regression adjusted for age, sex, and geographical area, males exhibited a higher likelihood compared to females [OR: 2.41, 95% CI, (2.21-2.62)]. Conclusions: Overall, this research suggests a connection between heightened environmental pesticide exposure due to increased agricultural use and autism.

Emerging evidence has demonstrated the impact of psychological stress on intestinal microbiota, however, the precise mechanisms are not fully understood. Enteric glia, a unique type of peripheral glia found within the enteric nervous system (ENS), play an active role in enteric neural circuits and have profound effects on gut functions. In the present study, we tested the hypothesis that enteric glia are involved in the alterations in the intestinal microflora and barrier induced by chronic water-avoidance stress (WAS) in the gut.

Western blotting and immunohistochemical (IHC) staining were used to examine the expression of glial fibrillary acidic protein (GFAP), nitric oxide synthetase (NOS) and choline acety1transferase (ChAT) in colon tissues. 16S rDNA sequencing was performed to analyse the composition of the intestinal microbiota in rats. Changes in the tight junction proteins Occludin, Claudin1 and proliferating cell nuclear antigen (PCNA) in the colon tissues were detected after WAS. The abundance of Firmicutes, Proteobacteria, Lactobacillus and Lachnospiraceae_NK4A136 decreased significantly, whereas the abundance of Actinobacteria, Ruminococcaceae_UCG-005 and Christensenellaceae-R-7 increased significantly in stressed rats. Meanwhile, the expression of Occludin, Claudin1 and PCNA significantly decreased after WAS. Treatment with L-A-aminohexanedioic acid (L-AA), a gliotoxin that blunts astrocytic function, obviously decreased the abundance of Actinobacteria, Ruminococcaceae_UCG-005 and Christensenel-laceae_R-7 in stressed rats and significantly increased the abundance of Proteobacteria, Lactobacillus and Lachnospiraceae_NK4A136. In addition, the protein expression of colon Occludin, Claudin1, and PCNA increased after intraperitoneal injection of L-AA. Furthermore, the expression level of NOS in colon tissues was significantly decreased, whereas that of ChAT was significantly increased following L-AA treatment.

Our results showed that enteric glial cells may contribute to WAS-induced changes in the intestinal microbiota and barrier function by modulating the activity of NOS and cholinergic neurones in the ENS.

Both animal and human studies, though limited, showed that multi-strain probiotic supplementation may reduce the number of seizures and/or seizure severity. Here, we evaluated the effect of a single strain probiotic supplementation on seizure susceptibility, antiseizure efficacy of sodium valproate, and several behavioral parameters in mice.

Lactobacillus helveticus R0052 was given orally for 28 days. Its influence on seizure thresholds was evaluated in the ivPTZ- and electrically-induced seizure tests. The effect on the antiseizure potency of valproate was assessed in the scPTZ test. We also investigated the effects of probiotic supplementation on anxiety-related behavior (in the elevated plus maze and light/dark box tests), motor coordination (in the accelerating rotarod test), neuromuscular strength (in the grip-strength test), and spontaneous locomotor activity. Serum and brain concentrations of valproate as well as cecal contents of SCFAs and lactate were determined using HPLC method.

L. helveticus R0052 significantly increased the threshold for the 6 Hz-induced psychomotor seizure. There was also a slight increase in the threshold for myoclonic and clonic seizure in the ivPTZ test. L. helveticus R0052 did not affect the threshold for tonic seizures both in the maximal electroshock- and ivPTZ-induced seizure tests. No changes in the antiseizure potency of valproate against the PTZ-induced seizures were reported. Interestingly, L. helveticus R0052 increased valproate concentration in serum, but not in the brain. Moreover, L. helveticus R0052 did not produce any significant effects on anxiety-related behavior, motor coordination, neuromuscular strength, and locomotor activity. L. helveticus R0052 supplementation resulted in increased concentrations of total SCFAs, acetate, and butyrate.

Altogether, this study shows that a single-strain probiotic - L. helveticus R0052 may decrease seizure susceptibility and this effect can be mediated, at least in part, by increased production of SCFAs. In addition, L. helveticus R0052 may affect bioavailability of valproate, which warrants further investigations.

Emerging evidence supports the gut microbiota and the brain communication in general health. This axis may affect behavior through modulating neurotransmission, and thereby involve in the pathogenesis and/or progression of different neuropsychiatric disorders such as depression. Brain-derived neurotrophic factor and cAMP response element-binding protein known as CREB/BDNF pathway plays have critical functions in the pathogenesis of depression as the same of mechanisms related to antidepressants. However, the putative causal significance of the CREB/BDNF signaling cascade in the gut-brain axis in depression remains unknown. Also interventions such as probiotics supplementation and exercise can influence microbiome also improve bidirectional communication of gut and brain. In this review we aim to explain the BDNF/CREB signaling pathway and gut microbiota dysfunction and then evaluate the potential role of probiotics, prebiotics, and exercise as a therapeutic target in the gut microbiota dysfunction induced depression. The current narrative review will specifically focus on the impact of exercise and diet on the intestinal microbiota component, as well as the effect that these therapies may have on the microbiota to alleviate depressive symptoms. Finally, we look at how BDNF/CREB signaling pathway may exert distinct effects on depression and gut microbiota dysfunction.