Microbiota Gut Brain Research Articles

Lactobacillus Helveticus Improves Controlled Cortical Impact Injury-Generated Neurological Aberrations by Remodeling of Gut-Brain Axis Mediators.

Considerable studies augured the potential of gut microbiota-based interventions in brain injury-associated complications. Based on our earlier study results, we envisaged the sex-specific neuroprotective effect of Lactobacillus helveticus by remodeling of gut-brain axis. In this study, we investigated the effect of L. helveticus on neurological complications in a mouse model of controlled cortical impact (CCI). Adult, male and female, C57BL/6 mice underwent CCI surgery and received L. helveticus treatment for six weeks. Sensorimotor function was evaluated via neurological severity score and rotarod test. Long-term effects on anxiety-like behavior and cognition were assessed using the elevated-zero maze (EZM) and novel object recognition test (NORT). Brain perilesional area, blood, colon, and fecal samples were collected post-CCI for molecular biology analysis. CCI-operated mice displayed significant neurological impairments at 1-, 3-, 5-, and 7-days post-injury (dpi) and exhibited altered behavior in EZM and NORT compared to sham-operated mice. However, these behavioral changes were ameliorated in mice receiving L. helveticus. GFAP, Iba-1, TNF-α, and IL-1β expressions and corticotrophin-releasing hormone (CRH) levels were elevated in the perilesional cortex of CCI-operated male/female mice. These elevated biomarkers and decreased BDNF levels in both male/female mice were modified by L. helveticus treatment. Additionally, L. helveticus treatment restored altered short-chain fatty acids (SCFAs) levels in fecal samples and improved intestinal integrity but did not affect decreased plasma levels of progesterone and testosterone in CCI mice. These results indicate that L. helveticus exerts beneficial effects in the CCI mouse model by mitigating inflammation and remodeling of gut microbiota-brain mediators.

The gut microbiota-brain connection: insights into major depressive disorder and bipolar disorder

Major depressive disorder (MDD) and bipolar disorder (BD) are two of the most prevalent mood disorders that seriously jeopardize both physical and mental health. The current diagnosis of MDD and BD relies primarily on clinical symptoms. However, correctly differentiating between MDD and BD during depressive episode states remains a substantial clinical challenge. The human gut hosts a large and diverse microbiota, which plays a pivotal role in various physiological processes. Emerging evidence suggests that the gut microbiota (GM) exerts beneficial effects on mental health disorders, including MDD, BD, and schizophrenia, through the microbe-gut-brain axis (MGBA). In recent years, the relationship between GM and mood disorders has garnered considerable attention, leading to intensive research in this area. The MGBA is a bidirectional communication system between the gut and the brain. Growing evidence indicates that the brain can influence the GM, which in turn may modulate the brain through this axis. This review aims to explore the changes in the GM of patients with MDD and BD and evaluate the effects of different treatments on their GM, including medication, probiotic, prebiotic and synbiotic interventions, and fecal microbiota transplantation (FMT). By doing so, we seek to identify potential disease-specific biomarkers, improve differential diagnosis, and offer novel therapeutic avenues for these disorders.

Jianghua Kucha black tea containing theacrine attenuates depression-like behavior in CUMS mice by regulating gut microbiota-brain neurochemicals and cytokines

Theacrine and theaflavins are known for their potential to mitigate depression and cognitive impairment. Jianghua Kucha black tea (JH) contains both compounds, yet its antidepressant properties are seldom documented. This study evaluated the effects of JH on depression in chronic unpredictable mild stress (CUMS) mice and explored the underlying mechanisms through integrative analyses of gut microbiota and fecal metabolomics. JH was found to significantly alleviate CUMS-induced depression-like behavior by improving body weight, food intake, 1% sucrose preference, immobility time, and numbers of crossings and standings compared to Zhuyeqi black tea (ZYQ), which contains theaflavins. JH notably altered the gut microbiota composition, enriching genera such as Turicibacter, Faecalibaculum, Akkermansia, and Desulfovibrio, while inhibiting genera norank_f__Muribaculaceae and Lactobacillus. Additionally, JH modified the fecal metabolite profile, characterized by increased levels of several secondary bile acids (BAs) and decreased levels of several purine intermediate metabolites. Furthermore, JH upregulated levels of monoamine neurotransmitters (5-HT and DA) and brain-derived neurotrophic factor (BDNF), while downregulating pro-inflammatory cytokines IL-6 and TNF-α in brain tissue. These findings suggested that JH could mitigate CUMS-induced depression-like behavior, potentially by modulating gut microbiota composition and function, as well as brain neurochemicals and cytokines.

Characterization of Yeast Isolated from the Gut Microbiota of Tunisian Children with Autism Spectrum Disorder

Research on the microbiota–gut–brain axis in autism has primarily focused on bacteria, with limited attention to fungi. There is a growing interest in understanding the involvement of fungi, particularly Candida, in patients with autism spectrum disorder. The aim of this study was to assess the prevalence, antifungal susceptibility profiles and virulence factors of Candida isolates from the guts of Tunisian children with autism. Twenty-eight children with autism and forty-six controls were enrolled. Candida isolates from the faecal samples were identified using biochemical and molecular methods; antifungal susceptibility testing was determined by the EUCAST broth microdilution method and virulence factors, including biofilm formation, cell surface hydrophobicity and phospholipase and proteinase activities, were assessed in vitro. As a result, Candida was detected in 13 children with autism (46.4%) and 14 control children (30.4%). Candida albicans was found to be the most common species isolate in the faeces of both groups of children. Antifungal susceptibility profiles showed that one Candida isolate was resistant to amphotericin B and anidulafungin (3.7%), six were resistant to micafungin (22.2%) and five were resistant to fluconazole (18.5%). All Candida isolates were biofilm producers. Of the twenty-seven isolates, only four showed phospholipase activity (14.8%), eight showed aspartyl-proteinase activity (29.6%) and nine were hydrophobic (33.3%). These results highlight the presence of Candida in the guts of children with autism, as well as the ability to express multiple virulence factors and the antifungal resistance, and they emphasize the need for further studies to confirm intestinal Candida colonization and its potential role in autism.

The Potential Role of Polyphenol Supplementation in Preventing and Managing Depression: A Review of Current Research

Depression is a common mental illness that affects 5% of the adult population globally. The most common symptoms of depression are low mood, lack of pleasure from different activities, poor concentration, and reduced energy levels for an extended period, and it affects the emotions, behaviors, and overall well-being of an individual. The complex pathophysiology of depression presents challenges for current therapeutic options involving a biopsychosocial treatment plan. These treatments may have a delayed onset, low remission and response rates, and undesirable side effects. Researchers in nutrition and food science are increasingly addressing depression, which is a significant public health concern due to the association of depression with the increased incidence of cardiovascular diseases and premature mortality. Polyphenols present in our diet may significantly impact the prevention and treatment of depression. The primary mechanisms include reducing inflammation and oxidative stress, regulating monoamine neurotransmitter levels, and modulating the microbiota–gut–brain axis and hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis. This review summarizes recent advances in understanding the effects of dietary polyphenols on depression and explores the underlying mechanisms of these effects for the benefit of human health. It also highlights studies that are looking at clinical trials to help future researchers incorporate these substances into functional diets, nutritional supplements, or adjunctive therapy to prevent and treat depression.

Investigating brain–gut microbiota dynamics and inflammatory processes in an autistic-like rat model using MRI biomarkers during childhood and adolescence

Autism spectrum disorder (ASD) is characterized by social interaction deficits and repetitive behaviors. Recent research has linked that gut dysbiosis may contribute to ASD-like behaviors. However, the exact developmental time point at which gut microbiota alterations affect brain function and behavior in patients with ASD remains unclear. We hypothesized that ASD-related brain microstructural changes and gut dysbiosis induce metabolic dysregulation and proinflammatory responses, which collectively contribute to the social behavioral deficits observed in early childhood. We used an autistic-like rat model that was generated via prenatal valproic acid exposure. We analyzed brain microstructural changes using diffusion tensor imaging (DTI) and examined microbiota, blood, and fecal samples for inflammation biomarkers. The ASD model rats exhibited significant brain microstructural changes in the anterior cingulate cortex, hippocampus, striatum, and thalamus; reduced microbiota diversity (Prevotellaceae and Peptostreptococcaceae); and altered metabolic signatures. The shift in microbiota diversity and density observed at postnatal day (PND) 35, which is a critical developmental period, underscored the importance of early ASD interventions. We identified a unique metabolic signature in the ASD model, with elevated formate and reduced acetate and butyrate levels, indicating a dysregulation in short-chain fatty acid (SCFA) metabolism. Furthermore, increased astrocytic and microglial activation and elevated proinflammatory cytokines—interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α)—were observed, indicating immune dysregulation. This study provided insights into the complex interplay between the brain and the gut, and indicated DTI metrics as potential imaging-based biomarkers in ASD, thus emphasizing the need for early childhood interventions.

Oral Trehalose Intake Modulates the Microbiota–Gut–Brain Axis and Is Neuroprotective in a Synucleinopathy Mouse Model

Parkinson’s disease (PD) is a neurodegenerative disease affecting dopaminergic neurons in the nigrostriatal and gastrointestinal tracts, causing both motor and non-motor symptoms. This study examined the neuroprotective effects of trehalose. This sugar is confined in the gut due to the absence of transporters, so we hypothesized that trehalose might exert neuroprotective effects on PD through its action on the gut microbiota. We used a transgenic mouse model of PD (PrP-A53T G2-3) overexpressing human α-synuclein and developing GI dysfunctions. Mice were given water with trehalose, maltose, or sucrose (2% w/v) for 6.5 m. Trehalose administration prevented a reduction in tyrosine hydroxylase immunoreactivity in the substantia nigra (−25%), striatum (−38%), and gut (−18%) in PrP-A53T mice. It also modulated the gut microbiota, reducing the loss of diversity seen in PrP-A53T mice and promoting bacteria negatively correlated with PD in patients. Additionally, trehalose treatment increased the intestinal secretion of glucagon-like peptide 1 (GLP-1) by 29%. Maltose and sucrose, which break down into glucose, did not show neuroprotective effects, suggesting glucose is not involved in trehalose-mediated neuroprotection. Since trehalose is unlikely to cross the intestinal barrier at the given dose, the results suggest its effects are mediated indirectly through the gut microbiota and GLP-1.

Association of probiotics, prebiotics, synbiotics or yogurt supplement with prevalence and all-cause mortality of depression: NHANES 2005–2016

BackgroundA growing body of studies revealed that enteric dysbacteriosis could result in depression via the “gut–microbiota–brain axis” (GMBA). Whether probiotics, prebiotics, and synbiotics supplements could lessen the risk of depression is a topic attracting attention. This research was conducted to evaluate the relationship between probiotics, prebiotics, synbiotics, or yogurt supplements and depression with large cross-sectional data. MethodsAll data in our research was sourced from the National Health and Nutrition Examination Survey (NHANES) (2005–2016). Probiotics, prebiotics, synbiotics, and yogurt supplements were identified using Food Frequency Questionnaire (FFQ) and Dietary Supplement Use 30-Day (DSQ). We employed the Patient Health Questionnaire (PHQ-9) for evaluating depression. Logistic regression and the Kaplan-Meier curve were performed to examine the correlation between the supplements and depression, as well as mortality. ResultsA total of 17,745 adult participants were selected. The participants who supplemented probiotics, prebiotics, synbiotics, or yogurt products in the last 30 days showed a significantly lower depression rate compared with those who didn't. Specifically, the supplements could alleviate depressive symptoms including sad, anhedonia, sleep problems, fatigue, appetite changes, and psychomotor changes. This association was more prominent in specific populations such as the population aged 40–60 years, male, whites. The supplements also show more significant effects on increasing survival rates in patients with mild depression. LimitationCross-sectional analysis reveals correlative but not causative association. ConclusionBased on the analysis of NHANES data, our research highlights the positive effect the supplements have on preventing depression, relieving depressive symptoms and increasing survival rates. This effect varied across populations.

Mechanism of selenium-enriched Bacillus subtilis alleviating perfluorohexanoic acid toxicity in Carassius auratus through the microbiota–gut–brain axis

The extensive production and use of perfluorohexanoic acid (PFHxA) have established it as an emerging environmental pollutant on a global scale. Selenium has been shown to exert substantial antagonistic effects on harmful substances. Concurrently, probiotics may confer advantageous effects on the host's brain function by orchestrating modulation within the microbiota–gut–brain axis. However, despite the promising properties of selenium-enriched Bacillus subtilis, uncertainties persist regarding its impact on PFHxA and underlying mechanisms. This study evaluated the potential alleviating effects of selenium-enriched B. subtilis on brain damage in Carassius auratus exposed to PFHxA from the perspective of the microbiota–gut–brain axis. Supplementation with selenium-enriched B. subtilis significantly mitigated brain damage and memory loss in C. auratus. Nissl staining of the brain revealed that selenium-enriched B. subtilis mitigated neuronal damage induced by PFHxA. TUNEL staining of the intestine showed that selenium-enriched B. subtilis mitigated PFHxA-induced apoptosis, thus mitigating intestinal injury. Moreover, our study uncovered additional layers of complexity in the microbiota–gut–brain axis, as enhancements were noted in the gut microbiota. Concurrently, alterations in the expression of neurotransmitters and biomarkers associated with emotions, such as 5-hydroxytryptamine, Dopamine, Corticotropin Releasing Factor, Substance p, and ghrelin, highlighted the profound impact of selenium-enriched B. subtilis on the intricate interplay between gut health and emotional well-being. Expanding our focus to the molecular level, we found that supplementation with selenium-enriched B. subtilis further inhibited cellular apoptosis through the brain-derived neurotrophic factor (BDNF) / Tyrosine Kinase receptor B (TrKB) / Protein Kinase B (AKT) / Glycogen synthase kinase3β (GSK-3β) pathway. In conclusion, supplementation with selenium-enriched B. subtilis is a promising strategy to mitigate PFHxA-induced brain damage in C. auratus, offering a multifaceted approach through the microbiota–gut–brain axis. In addition, our study introduces the potential of selenium-enriched B. subtilis as a valuable source of micronutrients for fish, opening new avenues for developmental considerations in aquaculture practices.

Long-term exposure to polystyrene microplastics reduces macrophages and affects the microbiota–gut–brain axis in mice

The remarkably increase in plastic use has led to worldwide pollution involving microplastics (MPs), which have been shown to be potentially hazardous substances. Although several studies have focused on the effects of small MPs on the brain and behavior of aquatic species, their effects on the mouse brain and the underlying mechanisms remain unclear. Our study’s aim was to investigate the effects of long-term oral ingestion of different sizes of MPs (0.1, 5, and 50 μm) on mouse colon tissue. Of these sizes, the smallest (0.1 μm) had the greatest effect. Pre-administration of MP promotes colitis but reduces tumor growth in a colitis-associated colorectal cancer (CAC) mouse mode. MPs can increase inflammation in mice via activation of the very late antigen 4–vascular cell adhesion molecule 1 (VLA4-VCAM1) signaling pathway in macrophages, while also inducing macrophage reduction in the late phase of inflammation. In the microbiota–gut–brain axis, polystyrene MP treatment altered bile acid and carbohydrate metabolism in the intestine, inhibited intestinal motility, reduced water reabsorption, and led to a certain degree of depression in mice. These findings suggest that small MPs can induce macrophage reduction, thereby affecting the physical and mental health by modulating the microbiota–gut–brain axis.

Microbiota-gut-brain axis in health and neurological disease: Interactions between gut microbiota and the nervous system.

Along with mounting evidence that gut microbiota and their metabolites migrate endogenously to distal organs, the 'gut-lung axis,' 'gut-brain axis,' 'gut-liver axis' and 'gut-renal axis' have been established. Multiple animal recent studies have demonstrated gut microbiota may also be a key susceptibility factor for neurological disorders such as Alzheimer's disease, Parkinson's disease and autism. The gastrointestinal tract is innervated by the extrinsic sympathetic and vagal nerves and the intrinsic enteric nervous system, and the gut microbiota interacts with the nervous system to maintain homeostatic balance in the host gut. A total of 1507 publications on the interactions between the gut microbiota, the gut-brain axis and neurological disorders are retrieved from the Web of Science to investigate the interactions between the gut microbiota and the nervous system and the underlying mechanisms involved in normal and disease states. We provide a comprehensive overview of the effects of the gut microbiota and its metabolites on nervous system function and neurotransmitter secretion, as well as alterations in the gut microbiota in neurological disorders, to provide a basis for the possibility of targeting the gut microbiota as a therapeutic agent for neurological disorders.

The role of gut microbiota metabolites in the regeneration and protection of nervous tissue: a narrative review

The gut microbiota modulates various physiological functions in the human body, including digestion, immune regulation, gut barrier maintenance, and even nervous system activity. The bidirectional communication between gut microbes and the brain, known as the microbiota–gut–brain axis, is crucial for balanced metabolism. Recent studies have indicated that gut microbiota metabolites, such as short-chain fatty acids, indole derivatives, neurotransmitters, and other bioactive compounds, can positively impact neurogenesis, myelination, and axonal regeneration, suggesting their potential in therapeutic strategies for neuroprotection and neuroregeneration. Despite the growing number of studies on gut microbiota metabolites, understanding their role in neuroprotective mechanisms remains limited. This article reviews the classification, production, functions and therapeutic potential of the most well-known gut microbiota metabolites, as well as their impact on neurogenesis, synaptogenesis, energy metabolism, immune modulation, and blood–brain barrier integrity, which will provide a foundation for the study of gut microbiota metabolites in the field of biomedical engineering.

Plant Extracts and ω-3 Improve Short-Term Memory and Modulate the Microbiota–Gut–Brain Axis in D-galactose Model Mice

BackgroundAging, characterized by a slow and progressive alteration of cognitive functions, is associated with gut microbiota dysbiosis, low-grade chronic inflammation, as well as increased oxidative stress and neurofunctional alterations. Some nutrients, such as polyphenols, carotenoids, and omega (ω)-3 (n–3), are good candidates to prevent age-related cognitive decline, because of their immunomodulatory, antioxidant, and neuroprotective properties. ObjectivesThe objective of this study was to demonstrate the preventive effect of a combination of plant extracts (PE) containing Memophenol™ (grapes and blueberries polyphenols) and a patented saffron extract (saffron carotenoids and safranal) and ω-3 on cognitive function in a mouse model of accelerated aging and to understand the biological mechanisms involved. MethodsWe used an accelerated-aging model by injecting 3-mo-old male C57Bl6/J mice with D-galactose for 8 wk, during which they were fed with a balanced control diet and supplemented or not with PE and/or ω-3 (n = 15–16/group). Short-term memory was evaluated by Y-maze test, following analyses of hippocampal and intestinal RNA expressions, brain fatty acid and oxylipin amounts, and gut microbiota composition (16S rRNA gene sequencing). Statistical analyses were performed (t test, analysis of variance, and Pearson correlation). ResultsOur results showed that oral administration of PE, ω-3, or both (mix) prevented hippocampus-dependent short-term memory deficits induced by D-galactose (P < 0.05). This effect was accompanied by the modulation of gut microbiota, altered by the treatment. PE and the mix increased the expression of antioxidative and neurogenesis markers, such as catalase and doublecortin, in hippocampus (P < 0.05 for both). Moreover, ω-3 and the mix showed a higher ω-3 amounts (P < 0.05) and EPA-derived 18- hydroxyeicosapentaenoic acid (P < 0.001) in prefrontal cortex. These changes may contribute to the improvement in memory. ConclusionsThese results suggest that the mix of PE and ω-3 could be more efficient at attenuating age-related cognitive decline than individual supplementations because it targeted, in mice, the different pathways impaired with aging.

Developing a novel hypothesis to enhance mental resilience via targeting Faecalibacterium prausnitzii in gut-brain axis

Social stress (SS) can lead to mental disorders (MD) in some people, such as depression and anxiety, while others who are resilient can handle SS without showing signs of mental illness. Resilience is characterized by human capacity to adapt to life’s adverse events without losing function or developing a mental disorder. Exploring molecular processes can help elucidate resilience mechanisms that counteract the pathophysiology of depression. Gut microbiome plays an essential role in the homeostasis of human body, especially the central nervous system (CNS). Therefore, it may support the counterbalance of certain disorders, such as depression, through the microbiota-gut-brain (MGB) axis. Short-chain fatty acids (SCFAs) produced by the gut microbiota, such as butyrate, increase the transmission activity of neurotransmitters, brain-derived neurotrophic factor (BDNF) expression and the regulation of microglia maturation enhances resilience in response to stress. Probiotics can be engineered to yield more butyrate. However, the overproduction of SCFAs is not necessarily beneficial and may lead to known side effects, such as intestinal dysbiosis or metabolic dysfunction. Herein, as we hypothesized the potential effect of the microbiome in resilience promotion, we have designed a cortisol-sensitive operon that allows gut microbiota to regulate the production of SCFAs according to the environmental demands which produces butyrate only when responding to stress. Amongst gut bacteria, Faecalibacterium prausnitzii (F. prausnitzii) has large amounts of butyrate and can be manipulated by designed plasmid, a process which makes it a suitable candidate to be translated into clinic.

Investigating the modulation of the endocannabinoid system by probiotic Lactiplantibacillus plantarum IMC513 in a zebrafish model of di-n-hexyl phthalate exposure

Environmental pollutants used as plasticizers in food packaging and in thousands of everyday products have become harmful for their impact on human health. Among them, phthalates, recognized as emerging endocrine disruptors (EDs) can induce toxic effects leading to different health disorders. Only few studies evaluated the effects of di-n-hexyl phthalate (DnHP) in in vivo models and no studies have been conducted to investigate the effect of DnHP on the endocannabinoid system (ECS), one of the majors signaling pathways involved in the microbiota–gut–brain axis. Due to the current relevance of probiotic bacteria as beneficial dietary interventions, the present study was aimed at evaluating the potential neuroprotective impact of daily administration of Lactiplantibacillus (Lpb.) plantarum IMC513 on zebrafish adults exposed to DnHP, with a focus on ECS modulation. Gene expression analysis revealed a promising protective role of probiotic through the restoration of ECS genes expression to the control level, in the brain of zebrafish daily exposed to DnHP. In addition, the levels of main endocannabinoids were also modulated. These findings confirm the potential ability of probiotics to interact at central level by modulating the ECS, suggesting the use of probiotics as innovative dietary strategy to counteract alterations by EDs exposure.

Gut microbiota-brain bile acid axis orchestrates aging-related neuroinflammation and behavior impairment in mice

Emerging evidence shows that disrupted gut microbiota-bile acid (BA) axis is critically involved in the development of neurodegenerative diseases. However, the alterations in spatial distribution of BAs among different brain regions that command important functions during aging and their exact roles in aging-related neurodegenerative diseases are poorly understood. Here, we analyzed the BA profiles in cerebral cortex, hippocampus, and hypothalamus of young and natural aging mice of both sexes. The results showed that aging altered brain BA profiles sex- and region- dependently, in which TβMCA was consistently elevated in aging mice of both sexes, particularly in the hippocampus and hypothalamus. Furthermore, we found that aging accumulated-TβMCA stimulated microglia inflammation in vitro and shortened the lifespan of C. elegans, as well as behavioral impairment and neuroinflammation in mice. In addition, metagenomic analysis suggested that the accumulation of brain TβMCA during aging was partially attributed to reduction in BSH-carrying bacteria. Finally, rejuvenation of gut microbiota by co-housing aged mice with young mice restored brain BA homeostasis and improved neurological dysfunctions in natural aging mice. In conclusion, our current study highlighted the potential of improving aging-related neuro-impairment by targeting gut microbiota-brain BA axis.

The Influence of Cecal Microbiota Transplantation on Chicken Injurious Behavior: Perspective in Human Neuropsychiatric Research.

Numerous studies have evidenced that neuropsychiatric disorders (mental illness and emotional disturbances) with aggression (or violence) pose a significant challenge to public health and contribute to a substantial economic burden worldwide. Especially, social disorganization (or social inequality) associated with childhood adversity has long-lasting effects on mental health, increasing the risk of developing neuropsychiatric disorders. Intestinal bacteria, functionally as an endocrine organ and a second brain, release various immunomodulators and bioactive compounds directly or indirectly regulating a host's physiological and behavioral homeostasis. Under various social challenges, stress-induced dysbiosis increases gut permeability causes serial reactions: releasing neurotoxic compounds, leading to neuroinflammation and neuronal injury, and eventually neuropsychiatric disorders associated with aggressive, violent, or impulsive behavior in humans and various animals via a complex bidirectional communication of the microbiota-gut-brain (MGB) axis. The dysregulation of the MGB axis has also been recognized as one of the reasons for the prevalence of social stress-induced injurious behaviors (feather pecking, aggression, and cannibalistic pecking) in chickens. However, existing knowledge of preventing and treating these disorders in both humans and chickens is not well understood. In previous studies, we developed a non-mammal model in an abnormal behavioral investigation by rationalizing the effects of gut microbiota on injurious behaviors in chickens. Based on our earlier success, the perspective article outlines the possibility of reducing stress-induced injurious behaviors in chickens through modifying gut microbiota via cecal microbiota transplantation, with the potential for providing a biotherapeutic rationale for preventing injurious behaviors among individuals with mental disorders via restoring gut microbiota diversity and function.

Brain-Gut and Microbiota-Gut-Brain Communication in Type-2 Diabetes Linked Alzheimer's Disease.

The gastrointestinal (GI) tract, home to the largest microbial population in the human body, plays a crucial role in overall health through various mechanisms. Recent advancements in research have revealed the potential implications of gut-brain and vice-versa communication mediated by gut-microbiota and their microbial products in various diseases including type-2 diabetes and Alzheimer's disease (AD). AD is the most common type of dementia where most of cases are sporadic with no clearly identified cause. However, multiple factors are implicated in the progression of sporadic AD which can be classified as non-modifiable (e.g., genetic) and modifiable (e.g. Type-2 diabetes, diet etc.). Present review focusses on key players particularly the modifiable factors such as Type-2 diabetes (T2D) and diet and their implications in microbiota-gut-brain (MGB) and brain-gut (BG) communication and cognitive functions of healthy brain and their dysfunction in Alzheimer's Disease. Special emphasis has been given on elucidation of the mechanistic aspects of the impact of diet on gut-microbiota and the implications of some of the gut-microbial products in T2D and AD pathology. For example, mechanistically, HFD induces gut dysbiosis with driven metabolites that in turn cause loss of integrity of intestinal barrier with concomitant colonic and systemic chronic low-grade inflammation, associated with obesity and T2D. HFD-induced obesity and T2D parallel neuroinflammation, deposition of Amyloid β (Aβ), and ultimately cognitive impairment. The review also provides a new perspective of the impact of diet on brain-gut and microbiota-gut-brain communication in terms of transcription factors as a commonly spoken language that may facilitates the interaction between gut and brain of obese diabetic patients who are at a higher risk of developing cognitive impairment and AD. Other commonality such as tyrosine kinase expression and functions maintaining intestinal integrity on one hand and the phagocytic clarence by migratory microglial functions in brain are also discussed. Lastly, the characterization of the key players future research that might shed lights on novel potential pharmacological target to impede AD progression are also discussed.

The role of gut microbiota in chronic restraint stress-induced cognitive deficits in mice

BackgroundChronic stress induces cognitive deficits. There is a well-established connection between the enteric and central nervous systems through the microbiota-gut-brain (MGB) axis. However, the effects of the gut microbiota on cognitive deficits remain unclear. The present study aimed to elucidate the microbiota composition in cognitive deficits and explore its potential in predicting chronic stress-induced cognitive deficits.MethodsMice were randomly divided into control and chronic restraint stress (CRS) groups. The mice subjected to CRS were further divided into cognitive deficit (CRS-CD) and non-cognitive deficit (CRS-NCD) groups using hierarchical cluster analysis of novel object recognition test results. The composition and diversity of the gut microbiota were analyzed.ResultsAfter being subjected to chronic restraint distress, the CRS-CD mice travelled shorter movement distances (p = 0.034 vs. CRS-NCD; p < 0.001 vs. control) and had a lower recognition index than the CRS-NCD (p < 0.0001 vs. CRS-NCD; p < 0.0001 vs. control) and control mice. The results revealed that 5 gut bacteria at genus levels were significantly different in the fecal samples of mice in the three groups. Further analyses demonstrated that Muricomes were not only significantly enriched in the CRS-CD group but also correlated with a decreased cognitive index. The area under the receiver operating curve of Muricomes for CRS-induced cognitive deficits was 0.96.ConclusionsOur study indicates that the composition of the gut microbiota is involved in the development of cognitive deficits induced by chronic restraint stress. Further analysis revealed that Muricomes have the potential to predict the development of chronic stress-induced cognitive deficits in mice.

The role of the microbiota–gut–brain axis in methamphetamine-induced neurotoxicity: Disruption of microbial composition and short-chain fatty acid metabolism

Methamphetamine (METH) abuse is associated with significant neurotoxicity, high addiction potential, and behavioral abnormalities. Recent studies have identified a connection between the gut microbiota and METH-induced neurotoxicity and behavioral disorders. However, the underlying causal mechanisms linking the gut microbiota to METH pathophysiology remain largely unexplored. In this study, we employed fecal microbiota transplantation (FMT) and antibiotic (Abx) intervention to manipulate the gut microbiota in mice administered METH. Furthermore, we supplemented METH-treated mice with short-chain fatty acids (SCFAs) and pioglitazone (Pio) to determine the protective effects on gut microbiota metabolism. Finally, we assessed the underlying mechanisms of the gut–brain neural circuit in vagotomized mice. Our data provide compelling evidence that modulation of the gut microbiome through FMT or microbiome knockdown by Abx plays a crucial role in METH-induced neurotoxicity, behavioral disorders, gut microbiota disturbances, and intestinal barrier impairment. Furthermore, our findings highlight a novel prevention strategy for mitigating the risks to both the nervous and intestinal systems caused by METH, which involves supplementation with SCFAs or Pio.