Brain Axis Research Articles

Microbiota-Gut-Brain Axis in Age-Related Neurodegenerative Diseases.

Age-related neurodegenerative diseases (NDs) pose a formidable challenge to healthcare systems worldwide due to their complex pathogenesis, significant morbidity, and mortality. Scope and Approach: This comprehensive review aims to elucidate the central role of the microbiotagut- brain axis (MGBA) in ND pathogenesis. Specifically, it delves into the perturbations within the gut microbiota and its metabolomic landscape, as well as the structural and functional transformations of the gastrointestinal and blood-brain barrier interfaces in ND patients. Additionally, it provides a comprehensive overview of the recent advancements in medicinal and dietary interventions tailored to modulate the MGBA for ND therapy. Accumulating evidence underscores the pivotal role of the gut microbiota in ND pathogenesis through the MGBA. Dysbiosis of the gut microbiota and associated metabolites instigate structural modifications and augmented permeability of both the gastrointestinal barrier and the blood-brain barrier (BBB). These alterations facilitate the transit of microbial molecules from the gut to the brain via neural, endocrine, and immune pathways, potentially contributing to the etiology of NDs. Numerous investigational strategies, encompassing prebiotic and probiotic interventions, pharmaceutical trials, and dietary adaptations, are actively explored to harness the microbiota for ND treatment. This work endeavors to enhance our comprehension of the intricate mechanisms underpinning ND pathogenesis, offering valuable insights for the development of innovative therapeutic modalities targeting these debilitating disorders.

Sex-bias metabolism of fetal organs, and their relationship to the regulation of fetal brain-placental axis.

The placenta plays influential role in the fetal development of mammals. But how the metabolic need of the fetal organs is related to that of the placenta, and whether this relationship is influenced by the sex of the fetus remain poorly understood. This study used pigs to investigate metabolomic signatures of male and female fetal organs, and determine the relevance of gene expression of the placenta and brain to the metabolism of peripheral organs. Untargeted metabolomics analysis was performed with the day-45 placenta, kidney, heart, liver, lung and brain of male and female pig fetuses to model sex differences in themetabolism of the peripheral organs relative to that of the brain and placenta. Transcriptomic analysis was performed to investigate the expression of metabolic genes in the placenta and fetal brain of both sexes. The results of this study show that the fetoplacental metabolic regulation was not only influenced by the fetal sex but also dependent on the metabolic requirement of theindividual organs of the fetus. Neural network modeling of metabolomics data revealed differential relationship of the metabolic changes of the peripheral organs with the placenta and fetal brain between males and females. RNA sequencing further showed that genes associated with themetabolism of the peripheral organs were differentially expressed in the placenta and fetal brain. The findings of this study suggest a regulatory role of the fetal brain and placenta axis in the sex-bias metabolism of the peripheral organs.

Pre and Probiotics to Postbiotics: A Changing Paradigm

The relationship between microbiota and human health has long been stated by Hippocrates said, “Death sits in the bowls” in 400 B.C. With recent scientific advance ments, there is a growing understanding of the significance of microbiota in health and disease. The two-way communication between the host and the microbiota involves the production of various metabolites that play crucial roles in host energy metabolism, influence nervous system function and the gut- brain axis, immune maturation and homeostasis, maintenance of mucosal integrity, treatment of metabolic disorders, anti-obesity, cholesterol lowering, antioxidant, anticancer, antiproliferative and anti-inflammatory properties. Postbiotics are inanimate microorganisms or their compounds, including short-chain fatty acids, exopolysaccharides, vitamins, teichoic acids, bacteriocins, enzymes and peptides that provide health benefits to the host. Postbiotics can be stored under normal environmental conditions, have a prolonged shelf life, easy to transport, and handle and overcome the limitations of probiotic use. As a result, postbiotics have immense potential as a safe and effective means of promoting health and well-being.

Dietary Supplements and the Gut–Brain Axis: A Focus on Lemon, Glycerin, and Their Combinations

Dietary supplements are products taken orally, and they contain an ingredient intended to augment the diet. Many studies demonstrate clear alterations in microbe abundances and the production of microbiota-derived metabolites, such as short-chain fatty acids, following dietary changes. This review comprehensively explores the possible interactions among gut microbiota, lemon extracts, glycerin, and their mixture products. Lemon extracts/components are associated with a vast array of health benefits, including anti-inflammation, antioxidant, anti-atherosclerotic, and anti-diabetic effects. They are also associated with increased memory and decreased depression. Glycerin can reduce serum free fatty acids and mimic caloric restriction; its metabolites can function as a broad-spectrum antimicrobial. Additionally, glycerin has a dehydrating effect on the central nervous system and can reduce focal cerebral edema and improve performance by expanding plasma volume. However, it may also have side effects, such as hyperglycemia. Therefore, combined consumption of lemon extracts and glycerin may, in part, mitigate each other’s side effects while exerting their benefits. There is growing evidence that both lemon components and glycerin are metabolized by the gut microbiota and may modulate the intestinal microbiome composition. Therefore, gut microbiome alterations are also explored as an important mechanism in the gut–brain axis regulating various effects of these dietary supplements and their application in various noncommunicable neurological disorders.

Neuronutrition and Its Impact on Post-Stroke Neurorehabilitation: Modulating Plasticity Through Diet

The recovery of neurological deficits after ischemic stroke largely depends on the brain’s ability to reorganize its undamaged neuronal circuits and neuronal plasticity phenomena. The consolidated evidence highlights the involvement of the patient’s impaired nutritional conditions in post-stroke recovery and unsatisfying rehabilitative outcomes. Standardized nutritional protocols usually applied in hospitalized patients in a rehabilitation setting aim mainly to improve the general health conditions of patients, do not consider the high inter-individual variability in neurorehabilitation outcomes, and are not sufficiently modifiable to provide neuroprotective and restorative dietary patterns that could promote neuronal plasticity and functional recovery during neurorehabilitation. Neuronutrition, an emergent scientific field of neuroscience, represents a valid model of a personalized nutritional approach, assuring, for each patient, nutrients having antioxidant and anti-inflammatory properties, ensuring a balanced microbiota composition, and providing adequate neurotrophic support, essential for improving neuronal plasticity, brain functional recovery, and rehabilitative outcomes. In the present narrative review, we provide an overview of the current knowledge on neuronutrition as an adjuvant strategy of a personalized nutritional approach potentially effective in improving post-stroke neuroplasticity and neurorehabilitation by counteracting or at least limiting post-stroke oxidative/nitrosative stress, neuroinflammation, and gut–brain axis disturbance.

Convergence of Neuroinflammation, Microbiota, and Parkinson’s Disease: Therapeutic Insights and Prospects

Parkinson’s disease (PD) is a complex neurodegenerative disorder. Recent evidence reveals connections between neuroinflammatory processes and intestinal microbiota alterations in the progression of this pathology. This comprehensive review explores the intricate relationships between them, highlighting their combined impact on PD. Neuroinflammation, characterized by immune activation in the central nervous system, is increasingly acknowledged as a critical factor in the development of PD. Concurrently, alterations in the gut microbiota composition have been linked to PD, suggesting a potential modulatory role in disease progression. Thus, bidirectional communication along the gut–brain axis has become pivotal in comprehending the pathogenesis of PD. Furthermore, we explore emerging therapeutic strategies that target these interconnected pathways, providing insights into potential avenues for PD treatment. The elucidation of these intricate relationships establishes a promising foundation for innovative therapeutic strategies aimed at altering disease progression and improving the quality of life for individuals affected by PD.

Use of Caenorhabditis elegans to Unravel the Tripartite Interaction of Kynurenine Pathway, UPRmt and Microbiome in Parkinson’s Disease

The model organism Caenorhabditis elegans and its relationship with the gut microbiome are gaining traction, especially for the study of neurodegenerative diseases such as Parkinson’s Disease (PD). Gut microbes are known to be able to alter kynurenine metabolites in the host, directly influencing innate immunity in C. elegans. While the mitochondrial unfolded protein response (UPRmt) was first characterized in C. elegans in 2007, its relevance in host–microbiome interactions has only become apparent in recent years. In this review, we provide novel insights into the current understanding of the microbiome–gut–brain axis with a focus on tripartite interactions between the UPRmt, kynurenine pathway, and microbiome in C. elegans, and explore their relationships for PD remediations.

UHT Cow’s Milk Supplementation Affects Cell Niches and Functions of the Gut–Brain Axis in BALB/c Mice

Background/Objectives: Cow’s milk is a bioactive cocktail with essential nutritional factors that is widely consumed during early childhood development. However, it has been associated with allergic responses and immune cell activation. Here, we investigate whether cow’s milk consumption regulates gut–brain axis functions and affects patterns of behaviors in BALB/c mice, previously described by present low sociability, significant stereotypes, and restricted interest features. The major objectives consist of to investigate cow’s milk supplementation as possible triggers interfering with cellular niches of the gut–brain axis and behavioral patterns. Methods: Male BALB/c at 6 weeks were randomly divided into two groups, one supplemented with cow’s milk processed at ultra-high temperature (UHT) and another group receiving water (controls) three times per day (200 μL per dose) for one week. Results: Milk consumption disturbed histological compartments of the small intestine, including niches of KI67+-proliferating cells and CD138+ Ig-secreting plasma cells. In the liver, milk intake was associated with pro-inflammatory responses, oxidative stress, and atypical glycogen distribution. Milk-supplemented mice showed significant increase in granulocytes (CD11b+SSChigh cells) and CD4+ T cells in the blood. These mice also had neuroinflammatory signals, including an enhanced number of cortical Iba-1+ microglial cells in the brain and significant cerebellar expression of nitric oxide synthase 2 by Purkinje cells. These phenotypes and tissue disorders in milk-supplemented mice were associated with atypical behaviors, including low sociability, high restricted interest, and severe stereotypies. Moreover, synaptic niches were also disturbed after milk consumption, and Shank-3+ and Drebrin+ post-synaptic cells were significantly reduced in the brain of these mice. Conclusions: Together, these data suggest that milk consumption interfered with the gut–brain axis in BALB/c mice and increased atypical behaviors, at least in part, linked to synapse dysfunctions, neuroinflammation, and oxidative stress regulation.

Exploring the Frontier: The Human Microbiome’s Role in Rare Childhood Neurological Diseases and Epilepsy

Emerging research into the human microbiome, an intricate ecosystem of microorganisms residing in and on our bodies, reveals that it plays a pivotal role in maintaining our health, highlighting the potential for microbiome-based interventions to prevent, diagnose, treat, and manage a myriad of diseases. The objective of this review is to highlight the importance of microbiome studies in enhancing our understanding of rare genetic epilepsy and related neurological disorders. Studies suggest that the gut microbiome, acting through the gut–brain axis, impacts the development and severity of epileptic conditions in children. Disruptions in microbial composition can affect neurotransmitter systems, inflammatory responses, and immune regulation, which are all critical factors in the pathogenesis of epilepsy. This growing body of evidence points to the potential of microbiome-targeted therapies, such as probiotics or dietary modifications, as innovative approaches to managing epilepsy. By harnessing the power of the microbiome, we stand to develop more effective and personalized treatment strategies for children affected by this disease and other rare neurological diseases.

Probiotics and Prebiotics for the Treatment of Irritable Bowel Syndrome—A Narrative Review

Background/Objectives: Gastrointestinal functional disorders (GFDs), including irritable bowel syndrome (IBS), are imbalances in the gut–brain axis characterized by persistence of symptoms in the abdominal area. Probiotics are live microorganisms that provide benefits to the health of their hosts when administered in adequate amounts, while prebiotics are a substrate that is selectively used by host microorganisms. This narrative review aimed to evaluate the effectiveness of prebiotics and probiotics mostly in irritable bowel syndrome, particularly on issues such as the interaction between these products and the gut microbiota, the duration of supplementation and long-term effects, the definition of ideal dosages, and the regulation and quality control of these products. Methods: A bibliographic search was carried out in indexed databases and articles published within 10 years before the beginning of the study and publications in English language, which investigated the specific theme of the study were considered. Papers dealing with topics not covered by the research questions, or presenting errors related with the wrong population or the wrong methods, as well as experimental studies and case reviews were excluded. Fifty-five articles were selected, initially in isolation by the authors and, afterward, under consensus. Results: It was possible to observe the effectiveness mainly of probiotics, in improving specific symptoms of the respective disorder; however, the available data remain unclear due to limitations concerning samples and methods of the studies evaluated. Conclusions: Despite evidence suggestive of therapeutic efficacy, additional multicenter randomized controlled trials (RCTs) with better defined protocols are still necessary to fill in the gaps in this subject, define measures to ensure the safe administration of these products, and confirm their therapeutic potential.

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.

Associations of Microbiota and Nutrition with Cognitive Impairment in Diseases

Background/Objectives: Recent research highlights the growing interest in the impact of nutrition on cognitive health and function in disease, as dietary habits are increasingly recognized as crucial factors in relation to brain function. This focus is especially important given the rising prevalence of neurodegenerative diseases and the cognitive decline associated with poor dietary choices. Links are now being sought between brain function and the microbiota and gut–brain axis. Mechanisms are proposed that include low-grade chronic neuroinflammation, the influence of short-chain fatty acids, or the disruption of glial cells and transmitters in the brain. Methods: We reviewed the articles on pubmed. This is not a systematic review, but of the narrative type. We wanted to outline the issue and summarise the latest information. Results: The axis in question has its foundation in nutrition. It has been reported that diet, particularly the components and the timing of food intake, has an impact on cognitive processes. The Mediterranean diet is most often cited in the literature as being beneficial to health. In order to obtain a more complete view, it is worth considering other dietary patterns, even those that impair our health. Conclusions: Determining what is beneficial and what is not will allow us to develop a speronized strategy for the prevention of, and fight against, cognitive impairment. Appropriately selected supplements, the functions of which we have also discussed, may prove supportive.

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.

Probiotic supplementation for reducing psychological symptoms in cancer patients on chemotherapy: A pilot trial

BackgroundPsychological disorders, including depression, anxiety, and stress, are prevalent among cancer patients undergoing chemotherapy. Probiotics have been investigated as a potential supplement to modulate the gut–brain axis and improve psychological symptoms, possibly through mechanisms such as serotonin regulation. However, studies on the effects of probiotics on psychological symptoms in chemotherapy patients are limited. MethodsThis randomised, double-blinded, placebo-controlled pilot trial was conducted at the outpatient clinic of dr. Kariadi Hospital, Semarang, in 2023. Sixty-one cancer patients undergoing chemotherapy were enrolled and randomised into an intervention (n = 30) and control (n = 31) group. The intervention group received probiotics (Lactobacillus rhamnosus Rosell-11 and Lactobacillus helveticus Rosell-52) twice daily for eight weeks. The primary outcomes were changes in depression, anxiety, and stress levels measured by the Depression, Anxiety, and Stress Scale 42 (DASS-42). The secondary outcome was serum serotonin levels. ResultsThe intervention group showed a significant decrease in total DASS-42 scores (p = 0.001), indicating an overall reduction in psychological distress. However, changes in the scores of the subscales (depression, anxiety, and stress) were not statistically significant (p > 0.05). Serum serotonin levels increased in the intervention group, but this was not statistically significant (p = 0.38). The findings should be interpreted cautiously due to small sample size and potential confounding factors. ConclusionThis pilot study suggests that eight weeks of probiotic supplementation may reduce overall psychological symptoms in cancer patients undergoing chemotherapy. Larger trials with rigorous controls and longer interventions are needed to confirm these preliminary findings.

Regulation of histidine metabolism by Lactobacillus Reuteri mediates the pathogenesis and treatment of ischemic stroke

Increasing evidence has underscored the significance of post-stroke alterations along gut–brain axis, while its role in pathogenesis and treatment of ischemic stroke (IS) remains largely unexplored. This study aimed to elucidate the therapeutic effects and action targets of Panax notoginseng saponins (PNS) on IS and explore a novel pathogenesis and treatment strategy of IS via profiling the microbial community and metabolic characteristics along gut–brain axis. Our findings revealed for the first time that the therapeutic effect of PNS on IS was microbiota-dependent. Ischemia/reperfusion (I/R) modeling significantly down-regulated Lactobacilli in rats, and PNS markedly recovered Lactobacilli, particularly Lactobacillus reuteri (L.Reu). Metabolomics showed a significant reduction in serum histidine (HIS) in clinical obsolete IS patients and rehabilitation period I/R rats. Meanwhile, the L.Reu colonization in I/R rats exhibited significant neuroprotective activity and greatly increased HIS in serum, gut microbiota, and brain. Moreover, exogenous HIS demonstrated indirect neuroprotective effects through metabolizing to histamine. Notably, vagus nerve severance in I/R rats was performed to investigate HIS's neuroprotective mechanism. The results innovatively revealed that PNS could promote HIS synthesis in gut by enhancing L.Reu proportion, thereby increasing intracerebral HIS through peripheral pathway. Consequently, our data provided novel insights into HIS metabolism mediated by L.Reu in the pathogenesis and treatment of IS.

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.

Lactobacilli Cell-Free Supernatants Modulate Inflammation and Oxidative Stress in Human Microglia via NRF2-SOD1 Signaling

Microglia are macrophage cells residing in the brain, where they exert a key role in neuronal protection. Through the gut–brain axis, metabolites produced by gut commensal microbes can influence brain functions, including microglial activity. The nuclear factor erythroid 2-related factor 2 (NRF2) is a key regulator of the oxidative stress response in microglia, controlling the expression of cytoprotective genes. Lactobacilli-derived cell-free supernatants (CFSs) are postbiotics that have shown antioxidant and immunomodulatory effects in several in vitro and in vivo studies. This study aimed to explore the effects of lactobacilli CFSs on modulating microglial responses against oxidative stress and inflammation. HMC3 microglia were exposed to lipopolysaccaride (LPS), as an inflammatory trigger, before and after administration of CFSs from three human gut probiotic species. The NRF2 nuclear protein activation and the expression of NRF2-controlled antioxidant genes were investigated by immunoassay and quantitative RT-PCR, respectively. Furthermore, the level of pro- and anti-inflammatory cytokines was evaluated by immunoassay. All CFSs induced a significant increase of NRF2 nuclear activity in basal conditions and upon inflammation. The transcription of antioxidant genes, namely heme oxygenase 1, superoxide dismutase (SOD), glutathione-S transferase, glutathione peroxidase, and catalase also increased, especially after inflammatory stimulus. Besides, higher SOD1 activity was detected relative to inflamed microglia. In addition, CFSs pre-treatment of microglia attenuated pro-inflammatory TNF-α levels while increasing anti-inflammatory IL-10 levels. These findings confirmed that gut microorganisms’ metabolites can play a relevant role in adjuvating the microglia cellular response against neuroinflammation and oxidative stress, which are known to cause neurodegenerative diseases.Graphical Gut-brain crosstalk: molecular point of view. Metabolites contained in the supernatant derived from Lactobacilli can cross the gut barrier and reach the central nervous system, where they are taken up by microglial cells. They induce the activation of the NRF2 pathway and the production of inflammatory mediators. This interaction attenuates two important events: oxidation (with high levels of NRF2) and inflammation (with high levels of IL-10 and low levels of TNF-α).

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.

Topic modeling of neuropsychiatric diseases related to gut microbiota and gut brain axis using artificial intelligence based BERTopic model on PubMed abstracts

Gut microbiota play a crucial role in complex interactions of the gut brain axis between the gastrointestinal system and the central nervous system. The intricate network of bidirectional communication between the gut and brain, mediated through neural, hormonal, and immunological pathways, known as the gut-brain axis, has been implicated in the pathophysiology of several mental, neurological and behavioral disorders. Alterations in the gut microbiota composition, or dysbiosis, have been associated with disorders like Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Autism Spectrum Disorder, Ischemic Stroke, Eating Disorders, depression, anxiety, stress and addiction. In this study, a Python package BERTopic, based on Artificial Intelligence based Natural Language Processing using Transformer model BERT, specializing in topic modeling, was applied to abstracts of 3,482 PubMed articles published from year 2014 until May 2024, to explore the mental, neurological, and behavioral diseases influenced by the gut microbiota. There were some variations in individual runs of BERTopic due to stochastic nature of one of its components, but overall the discovered topics corresponded to major neuropsychiatric diseases. To understand the impact of the variability in outcomes ten repeated runs of BERTopic were performed with keeping identical parameters. The major topics that were found consistently in all the ten repeated runs of BERTopic were Depression, Alzheimer Disease, Autism Spectrum Disorder, Parkinson's Disease, Multiple Sclerosis, Ischemic Stroke, Anorexia Nervosa and Schizophrenia.