Gut-brain Research Articles

The gut-eye axis: from brain neurodegenerative diseases to age-related macular degeneration.

Age-related macular degeneration Is a serious neurodegenerativo disease of the retina that significantly impacts vision. Unfortunately, the specific pathogenesis remains unclear, and effective early treatment options are consequently lacking. The microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a host. The intestinal microbiome undergoes dynamic changes owing to age, diet, genetics, and other factors. Such dysregulation of the intestinal flora can disrupt the microecological balance, resulting in immunological and metabolic dysfunction in the host, and affecting the development of many diseases. In recent decades, significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract, including the brain. Indeed, several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Similarly, the role of the "gut-eye axis" has been confirmed to play a role in the pathogenesis of many ocular disorders. Moreover, age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable etiologies. As such, the intestinal flora may play an important role in age-related macular degeneration. Given the above context, the present review aims to clarify the gut-brain and gut-eye connections, assess the effect of intestinal flora and metabolites on age-related macular degeneration, and identify potential diagnostic markers and therapeutic strategies. Currently, direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited, while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular degeneration. Organ-on-a-chip technology has shown promise in clarifying the gut-eye interactions, while integrating analysis of the intestinal flora with research on metabolites through metabolomics and other techniques is crucial for understanding their potential mechanisms.

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.

New perspectives on microbiome-dependent gut-brain pathways for the treatment of depression with gastrointestinal symptoms: from bench to bedside.

Patients with depression are more likely to have chronic gastrointestinal (GI) symptoms than the general population, but such symptoms are considered only somatic symptoms of depression and lack special attention. There is a chronic lack of appropriate diagnosis and effective treatment for patients with depression accompanied by GI symptoms, and studying the association between depression and GI disorders (GIDs) is extremely important for clinical management. There is growing evidence that depression is closely related to the microbiota present in the GI tract, and the microbiota-gut-brain axis (MGBA) is creating a new perspective on the association between depression and GIDs. Identifying and treating GIDs would provide a key opportunity to prevent episodes of depression and may also improve the outcome of refractory depression. Current studies on depression and the microbially related gut-brain axis (GBA) lack a focus on GI function. In this review, we combine preclinical and clinical evidence to summarize the roles of the microbially regulated GBA in emotions and GI function, and summarize potential therapeutic strategies to provide a reference for the study of the pathomechanism and treatment of depression in combination with GI symptoms.

Beneficial Effects of Ginger Root Extract on Pain Behaviors, Inflammation, and Mitochondrial Function in the Colon and Different Brain Regions of Male and Female Neuropathic Rats: A Gut-Brain Axis Study.

Neuroinflammation and mitochondrial dysfunction have been implicated in the progression of neuropathic pain (NP) but can be mitigated by supplementation with gingerol-enriched ginger (GEG). However, the exact benefits of GEG for each sex in treating neuroinflammation and mitochondrial homeostasis in different brain regions and the colon remain to be determined. Evaluate the effects of GEG on emotional/affective pain and spontaneous pain behaviors, neuroinflammation, as well as mitochondria homeostasis in the amygdala, frontal cortex, hippocampus, and colon of male and female rats in the spinal nerve ligation (SNL) NP model. One hundred rats (fifty males and fifty females) were randomly assigned to five groups: sham + vehicle, SNL + vehicle, and SNL with three different GEG doses (200, 400, and 600 mg/kg BW) for 5 weeks. A rat grimace scale and vocalizations were used to assess spontaneous and emotional/affective pain behaviors, respectively. mRNA gene and protein expression levels for tight junction protein, neuroinflammation, mitochondria homeostasis, and oxidative stress were measured in the amygdala, frontal cortex, hippocampus, and colon using qRT-PCR and Western blot (colon). GEG supplementation mitigated spontaneous pain in both male and female rats with NP while decreasing emotional/affective responses only in male NP rats. GEG supplementation increased intestinal integrity (claudin 3) and suppressed neuroinflammation [glial activation (GFAP, CD11b, IBA1) and inflammation (TNFα, NFκB, IL1β)] in the selected brain regions and colon of male and female NP rats. GEG supplementation improved mitochondrial homeostasis [increased biogenesis (TFAM, PGC1α), increased fission (FIS, DRP1), decreased fusion (MFN2, MFN1) and mitophagy (PINK1), and increased Complex III] in the selected brain regions and colon in both sexes. Some GEG dose-response effects in gene expression were observed in NP rats of both sexes. GEG supplementation decreased emotional/affective pain behaviors of males and females via improving gut integrity, suppressing neuroinflammation, and improving mitochondrial homeostasis in the amygdala, frontal cortex, hippocampus, and colon in both male and female SNL rats in an NP model, implicating the gut-brain axis in NP. Sex differences observed in the vocalizations assay may suggest different mechanisms of evoked NP responses in females.

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.

Ghrelin in Depression: A Promising Therapeutic Target.

Depression is a widespread disease affecting over 300 million individuals of various ethnicities and socioeconomic backgrounds globally. It frequently strikes early in life and becomes a chronic or recurring lifelong illness. Out of the various hypotheses for the pathophysiology of depression, the gut-brain axis and stress hypothesis are the ones that need to be researched, as psychological stress impairs one or more pathways of the brain-gut axis and is likely to cause brain-gut axis dysfunction and depression. A dysfunctional reciprocal gut-brain relationship may contribute to many diseases, including inflammatory disorders, abnormal stress responses, impaired behavior, and metabolic changes. The hormone ghrelin is a topic of interest concerning the gut-brain axis as it interacts with the gut-brain axis indirectly via the central nervous system or via crossing the blood-brain barrier. Ghrelin release is also affected by the gut microbes, which has also been discussed in the review. This review elaborates on Ghrelin's role in depression and its effect on various aspects like neurogenesis, HPA axis, and neuroinflammation. Furthermore, this review focuses on ghrelin as a potential target for alleviation of depressive symptoms.

Limosilactobacillus-related 3-OMDP as a potential therapeutic target for depression

Objective Gut microbiota was closely involved in the pathogenesis of depression, but the underlying molecular mechanisms in depression remained unclear. This study was conducted to investigate the relationship between neurotransmitters/inflammatory factors and gut microbiota in depressed mice. Materials and methods A chronic social defeat stress (CSDS) depression model was established. Gut microbial composition was detected in faeces, neurotransmitters were detected in faeces, colon, blood and hippocampus, and inflammatory factors were detected in hippocampus. After a key neurotransmitter was identified, intervention experiment was conducted to explore whether it could improve depressive-like behaviours. Results Six differential genera in faeces, 14 differential neurotransmitters in gut-brain axis, and two differential inflammatory factors (interleukin-1 beta (IL-1β) and interleukin-6 (IL-6)) in hippocampus were identified in depressed mice. There were significant correlations among differential genera, differential neurotransmitters and IL-1β/IL-6. Among these differential neurotransmitters, 3-O-Methyldopa (3-OMDP) was found to be consistently decreased in faeces, colon, blood and hippocampus, and 3-OMDP was significantly correlated to Limosilactobacillus and IL-1β. After receiving 3-OMDP, the depressive-like behaviours in depressed mice were improved and the increased IL-1β/IL-6 levels were reversed. Conclusions These results indicated that gut microbiota might affect host’s inflammation levels in brain through regulating neurotransmitters, eventually leading to the onset of depression. ‘Limosilactobacillus-3-OMDP-IL-1β/IL-6’ might be a potential pathway in the crosstalk of gut and brain, and 3-OMDP held the promise as a therapeutic target for depression.

Addressing Mental Health in Rural Settings: A Narrative Review of Blueberry Supplementation as a Natural Intervention.

Depression and anxiety are major public health issues; however, there is an unmet need for novel, effective, and accessible treatments, particularly in rural communities. Blueberries are an unexplored nutraceutical for these conditions due to their excellent nutritional profile, with particularly high levels of polyphenols and anthocyanins and benefits on mood, cognition, and health. Here, we present a narrative review of the literature concerning the etiology and treatments of major depressive disorder (MDD) and generalized anxiety disorder (GAD). In both animal and human studies, blueberry supplementation can ameliorate behavioral symptoms of both anxiety and depression. The mechanistic underpinnings of these behavioral improvements are not fully defined, but likely involve biochemical alterations in the gut-brain axis, including to inflammatory cytokines, reactive oxygen species, and growth factors. We also review the limitations of traditional therapies in rural settings. Finally, we assess the potential benefit of nutraceutical interventions, particularly blueberries, as novel therapeutics for these distinct, yet related mental health issues.

The gut microbiota-brain axis role in neurodegenerative diseases and implications according to the sex

Recent advancements in neurodegenerative research have embraced a multisystemic approach, emphasizing the role of the gut microbiota and its interactions with various systems, including the central nervous system. This review explores the interactions between the gut-brain axis and neurological illnesses associated with ageing, with a particular focus on the potential influence of sex. Despite increased life expectancy, the chronological ceiling of human well-being remains unchanged, implying that conditions such as dementia and Parkinson's disease will continue to affect individuals for extended periods as lifespans increase. Understanding the microbiota-gut-brain axis in relation to neurodegenerative diseases may pave the way for novel therapeutic approaches. Additionally, emerging research suggests that sex-related variations in gut microbiota and the influence of sex hormones may impact the manifestation of several neurodegenerative conditions, including those related to mental health. This review updates the current knowledge on age-related neurodegenerative diseases, such as dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and dementia with Lewy bodies. Future research should focus on exploring microbial therapeutics for the treatment and prevention of age-related neurodegenerative disorders, as well as gender-specific variations in gut microbiota. In this context, the EU-funded project MEMOIR will investigate the impact of a healthy diet on gut microbiota and the progression of Mild Cognitive Impairment.

Aging-induced dysbiosis worsens sepsis severity but is attenuated by probiotics in D-galactose-administered mice with cecal ligation and puncture model.

Despite the well-established effects of aging on brain function and gut dysbiosis (an imbalance in gut microbiota), the influence of aging on sepsis-associated encephalopathy (SAE) and the role of probiotics in this context remain less understood. C57BL/6J mice (8-week-old) were subcutaneously administered with 8 weeks of D-galactose (D-gal) or phosphate buffer solution (PBS) for aging and non-aging models, respectively, with or without 8 weeks of oral Lacticaseibacillus rhamnosus GG (LGG). Additionally, the impact of the condition media from LGG (LCM) was tested in macrophages (RAW 264.7 cells), microglia (BV-2 cells), and hippocampal cells (HT-22 cells). Fecal microbiome analysis demonstrated D-gal-induced dysbiosis (reduced Firmicutes and Desulfobacterota with increased Bacteroidota and Verrucomicrobiota), which LGG partially neutralized the dysbiosis. D-gal also worsens cecal ligation and puncture (CLP) sepsis severity when compared with PBS-CLP mice, as indicated by serum creatinine (Scr) and alanine transaminase (ALT), but not mortality, neurological characteristics (SHIRPA score), and serum cytokines (TNF-α and IL-6). Additionally, D-gal-induced aging was supported by fibrosis in the liver, kidney, and lung; however, CLP sepsis did not worsen fibrosis. Interestingly, LGG attenuated all parameters (mortality, Scr, ALT, SHIRPA, and cytokines) in non-aging sepsis (PBS-CLP) while improving all these parameters, except for mortality and serum IL-6, in aging sepsis (D-gal CLP). For the in vitro test using lipopolysaccharide (LPS) stimulation, LCM attenuated inflammation in some parameters on RAW264.7 cells but not BV-2 and HT-22 cells, implying a direct anti-inflammatory effect of LGG on macrophages, but not in cells from the brain. D-gal induced fecal dysbiosis and worsened sepsis severity as determined by Scr and ALT, and LGG could alleviate most of the selected parameters of sepsis, including SAE. However, the impact of LGG on SAE was not a direct delivery of beneficial molecules from the gut to the brain but partly due to the attenuation of systemic inflammation through the modulation of macrophages.

Gut-Brain Axis and Psychopathology: Exploring the Impact of Diet with a Focus on the Low-FODMAP Approach.

The gut-brain axis (GBA) is a bidirectional communication network connecting the central nervous system with the gastrointestinal (GI) tract, influencing both mental and physical health. Recent research has underscored the significant role of diet in modulating this axis, with attention to how specific dietary patterns can impact anxiety and depression, particularly when linked to disorders of gut-brain interaction (DGBIs), like intestinal bowel syndrome (IBS). This narrative review examines the effects of specific diet regimens on the GBA and its potential role in managing psychopathology, focusing on anxiety and depression, IBS, and the low-FODMAP diet. We conducted a search on PubMed and MEDLINE by combining the following key terms: "Gut-Brain Axis", "Irritable Bowel Syndrome", "Low FODMAP diet", "Mediterranean Diet", "Psychopathology", "Anxiety and Depression", and "Gut Microbiota". We applied the following filters: "Clinical Trials", "Randomized Controlled Trials", "Reviews", "Meta-Analyses", and "Systematic Reviews". In total, 59 papers were included. Low-FODMAP diet, originally developed to alleviate GI symptoms in IBS, may also positively influence mental health by modulating the GBA and improving the gut microbiota (GM) composition. New insights suggest that combining the low-FODMAP diet with the Mediterranean diet could offer a synergistic effect, enhancing both GI and psychological therapeutic outcomes. Understanding the complex interactions between diet, the GM, and mental health opens new avenues for holistic approaches to managing psychopathology, particularly when linked to GI symptoms.

Multi-omics insights into the microbiota-gut-brain axis and cognitive improvement post-bariatric surgery

BackgroundAlthough numerous studies have shown that bariatric surgery results in sustained weight loss and modifications in gut microbiota composition and cognitive function, the exact underlying mechanisms are unclear. This study aimed to investigate the effects of bariatric surgery on cognitive function through the microbiota-gut-brain axis (MGBA).MethodsDemographic data, serum samples, fecal samples, cognitive assessment scales, and resting-state functional connectivity magnetic resonance imaging (rs-fMRI) scans were obtained from 39 obese patients before and after (6 months) laparoscopic sleeve gastrectomy (LSG). PCA analysis, OPLS-DA analysis, and permutation tests were used to conduct fecal 16 S microbiota profiling, serum metabolomics, and neuroimaging analyses, and a bariatric surgery-specific rs-fMRI brain functional connectivity network was constructed. Spearman correlation analysis and Co-inertia analysis were employed to correlate significant alterations in cognitive assessment scales and resting-state functional connectivity difference networks with differential serum metabolites and 16 S microbiota data to identify key gut microbiota and serum metabolic factors.ResultsLSG significantly reduced the weight of obese patients, with reductions of up to 28%. Furthermore, cognitive assessment scale measurements revealed that LSG enhanced cognitive functions, including memory (HVLT, p = 0.000) and executive function (SCWT, p = 0.008). Also, LSG significantly altered gut microbiota composition (p = 0.001), with increased microbial abundance and diversity (p < 0.05). Moreover, serum metabolite levels were significantly altered, revealing intergroup differences in 229 metabolites mapped to 72 metabolic pathways (p < 0.05, VIP > 1). Spearman correlation analysis among cognitive assessment scales, gut microbiota species, and serum metabolites revealed correlations with 68 gut microbiota species and 138 serum metabolites (p < 0.05). Furthermore, pairwise correlations were detected between gut microbiota and serum metabolites (p < 0.05). Functional neuroimaging analysis revealed that LSG increased functional connectivity in cognitive-related frontotemporal networks (FPN, p < 0.01). Additionally, normalization of the default mode network (DMN) and salience network (SN) connectivity was observed after LSG (p < 0.001). Further canonical correlation and correlation analysis suggested that the cognitive-related brain network changes induced by LSG were associated with key gut microbiota species (Akkermansia, Blautia, Collinsella, Phascolarctobacterium, and Ruminococcus, p < 0.05) and neuroactive metabolites (Glycine, L-Serine, DL-Dopa, SM (d18:1/24:1(15Z), p < 0.05).ConclusionThese findings indicate the pathophysiological role of the microbiota-gut-brain axis in enhancing cognitive function after bariatric surgery, and the study provides a basis for clinical dietary adjustments, probiotic supplementation, and guidance for bariatric surgery, but further research is still needed.Trial registrationChinese Clinical Trial Registry, ChiCTR2100049403. Registered 02 August 2021, https://www.chictr.org.cn/.

Identification of novel proteins in inflammatory bowel disease based on the gut-brain axis: a multi-omics integrated analysis

BackgroundThe gut-brain axis has garnered increasing attention, with observational studies suggesting its involvement in the disease activity and progression of inflammatory bowel disease (IBD), but the precise mechanisms remain unclear.Materials and methodsIn this study, we aimed to investigate “novel proteins” underlying IBD in the brain using a comprehensive multi-omics analysis approach. We performed integrated analyses of proteomics and transcriptomics in the human prefrontal cortex (PFC) tissue, coupled with genome-wide association studies (GWAS) of IBD, crohn’s disease (CD), and ulcerative colitis (UC). This included performing protein-wide association studies (PWAS), transcriptome-wide association studies (TWAS), Mendelian randomization (MR), and colocalization analysis to identify brain proteins associated with IBD and its subtypes.ResultsPWAS analyses identified and confirmation 9, 9, and 6 brain proteins strongly associated with IBD, CD, and UC, respectively. Subsequent MR analyses revealed that increased abundance of GPSM1, AUH, TYK2, SULT1A1, and FDPS, along with corresponding gene expression, led to decreased risk of IBD. For CD, increased abundance of FDPS, SULT1A1, and PDLIM4, along with corresponding gene expression, also decreased CD risk. Regarding UC, only increased abundance of AUH, along with corresponding gene expression, was significantly associated with decreased UC risk. Further TWAS and colocalization analyses at the transcriptome level supported strong associations of SULT1A1 and FDPS proteins with reduced risk of IBD and CD.ConclusionThe two “novel proteins,” SULT1A1 and FDPS, are strongly associated with IBD and CD, elucidating their causal relationship in reducing the risk of IBD and CD. This provides new clues for identifying the pathogenesis and potential therapeutic targets for IBD and CD.

Cannabis use disorder increases risk of large-artery atherosclerotic stroke and migraine with aura through mendelian randomization study

Observational studies have shown some association between cannabis use disorder (CUD) and neurological disorders, but their causal relationship is unclear. In this study, we tested the potential causal relationship between CUD and three common neurological disorders using two-sample Mendelian randomization (TSMR) and multivariate MR (MVMR) methods. Thirty-two genetic loci were extracted as exposure factors from the largest genome-wide association study (GWAS) summary statistics for CUD to date. TSMR results showed that genetic prediction of CUD with all stroke, ischemic stroke, large-artery atherosclerotic stroke, migraine with aura, and Alzheimer’s disease (AD) had a positive causal relationship (P < 0.05), which was not found in several other diseases. The association between CUD and stroke, ischemic stroke, and AD in the MVMR study may have been influenced by confounding factors (P > 0.05). Subgroup analyses highlighted a causal relationship between genetically predicted CUD and large-artery atherosclerotic stroke (OR = 1.169; 95%CI 1.030–1.328; P = 0.016) and migraine with aura (OR = 1.142; 95% 1.021–1.278; P = 0.020). Our further functional mapping and annotation enrichment analyses using FUMA suggest that the brain-gut axis may serve as another layer of explanation for the existence of an association between CUD and neurological disorders.

Comparative Analysis of Fecal Microbiota Between Adolescents with Early-Onset Psychosis and Adults with Schizophrenia.

Studies of the composition of the gut microbiome have consistently shown that psychiatric disorders such as schizophrenia are associated with gut dysbiosis. However, research focusing on adolescents with early-onset psychosis remains limited. This study aimed to characterize the microbial communities and their potential metabolic functions in these populations. We identified that genera Desulfovibrionaceae_Incertae_Sedis, Paraprevotella, and several genera from the Oscillospiraceae family were significantly more abundant in patients with schizophrenia compared to non-psychotic individuals, while Dorea showed decreased levels in schizophrenia patients. Furthermore, patients with early-onset psychosis demonstrated a significant reduction in Staphylococcus abundance. Additionally, we observed an increase in Prevotellaceae Leyella and Prevotellaceae Incertae Sedis in patients receiving atypical antipsychotic treatment, along with a rise in the genus Weissella among those treated with sertraline. Conversely, patients on valproate treatment exhibited decreased levels of Desulfovibrionaceae Incertae Sedis, while showing increased levels of Kandleria and Howardella. Functional prediction analysis using PICRUSt2 revealed significant differences in the expression of key enzymes associated with fatty acid metabolism. Gene orthology analysis identified 10 differentially expressed genes in the early-onset psychosis and schizophrenia groups. Our findings underscore the importance of considering dietary factors, pharmacological treatments, and microbial composition in understanding the gut-brain axis in psychiatric disorders.

Unravelling the neuroimmune nexus: insights into epilepsy pathology and the role of S100b protein in brain-gut axis modulation: a literature review.

Epilepsy, a chronic neurological condition marked by recurrent, unprovoked seizures, involves complex pathophysiological mechanisms. Recent advancements have expanded our understanding from traditional neuronal dysfunction to include neuroimmune interactions and the influence of the brain-gut-bio-axis. This review explores the role of the S100b protein within these contexts, noted for its involvement in neuroinflammatory processes and as a potential biomarker. Furthermore, it discusses the emerging significance of the gut microbiome in modulating neuroimmune responses and seizure activity. The review integrates findings from recent studies, emphasizing the critical role of the S100b signalling pathway and the gut-brain axis in epilepsy pathology. The interplay between neuroimmune mechanisms and gut microbiota offers novel insights and potential therapeutic targets, underlining the need for further research to exploit these connections for clinical benefit.

Nutritional Modulation of the Gut-Brain Axis: A Comprehensive Review of Dietary Interventions in Depression and Anxiety Management.

Mental health is an increasing topic of focus since more than 500 million people in the world suffer from depression and anxiety. In this multifactorial disorder, parameters such as inflammation, the state of the microbiota and, therefore, the patient's nutrition are receiving more attention. In addition, food products are the source of many essential ingredients involved in the regulation of mental processes, including amino acids, neurotransmitters, vitamins, and others. For this reason, this narrative review was carried out with the aim of analyzing the role of nutrition in depression and anxiety disorders. To reach the review aim, a critical review was conducted utilizing both primary sources, such as scientific publications and secondary sources, such as bibliographic indexes, web pages, and databases. The search was conducted in PsychINFO, MedLine (Pubmed), Cochrane (Wiley), Embase, and CinAhl. The results show a direct relationship between what we eat and the state of our nervous system. The gut-brain axis is a complex system in which the intestinal microbiota communicates directly with our nervous system and provides it with neurotransmitters for its proper functioning. An imbalance in our microbiota due to poor nutrition will cause an inflammatory response that, if sustained over time and together with other factors, can lead to disorders such as anxiety and depression. Changes in the functions of the microbiota-gut-brain axis have been linked to several mental disorders. It is believed that the modulation of the microbiome composition may be an effective strategy for a new treatment of these disorders. Modifications in nutritional behaviors and the use of ergogenic components are presented as important non-pharmacological interventions in anxiety and depression prevention and treatment. It is desirable that the choice of nutritional and probiotic treatment in individual patients be based on the results of appropriate biochemical and microbiological tests.

Unveiling the Potential of Gut Microbiota: Promising Approaches to Treat Drug-Resistant Epilepsy

Introduction: Epilepsy is a chronic, non-infectious disease of the brain. Data shows that even 70 million people worldwide suffer from it and one-third of them fail to control it with anti-epileptic drugs. The gut microbiota has an impact on the course of the disease. The microbiota mediates between the gastrointestinal system and the central nervous system.Purpose: The aim of the work is to analyse how modification of the gut microbiota affects patients with drug-resistant epilepsy.Material and method: In December 2023, an extensive search was conducted and articles found in the Medline (PubMed) databases were selected by using the following keywords: drug-resistant epilepsy, gut microbiota, gut-brain axis, ketogenic diet, probiotics, faecal microbiota transplantation, to focus on recent developments and advancements in the field, the search was limited to articles published between 2017 and 2023.Conclusions: The intestinal microbiota in drug-resistant epilepsy (DRE) patients differs from that of healthy individuals or drug-sensitive epilepsy patients. Acknowledging the presence of the gut-brain axis and its impact on the central nervous system, we can view altering the flora as a potential therapeutic approach for DRE patients. The ways in which microbiota changes have been confirmed by research include: ketogenic diet, antibiotics, probiotics and fecal microbiota transplantation (FMT). Modifying the microbiota through these mentioned methods is all promising for treating DRE.

Lactobacillus Eats Amyloid Plaque and Post-Biotically Attenuates Senescence Due to Repeat Expansion Disorder and Alzheimer's Disease.

Patients with Alzheimer's disease and related dementia (ADRD) are faced with a formidable challenge of focal amyloid deposits and cerebral amyloid angiopathy (CAA). The treatment of amyloid deposits in ADRD by targeting only oxidative stress, inflammation and hyperlipidemia has not yielded significant positive clinical outcomes. The chronic high-fat diet (HFD), or gut dysbiosis, is one of the major contributors of ADRD in part by disrupted transport, epigenetic DNMT1 and the folate 1-carbon metabolism (FOCM) cycle, i.e., rhythmic methylation/de-methylation on DNA, an active part of epigenetic memory during genes turning off and on by the gene writer (DNMT1) and eraser (TET2/FTO) and the transsulfuration pathway by mitochondrial 3-mercaptopyruvate sulfur transferase (3MST)-producing H2S. The repeat CAG expansion and m6A disorder causes senescence and AD. We aim to target the paradigm-shift pathway of the gut-brain microbiome axis that selectively inhibits amyloid deposits and increases mitochondrial transsulfuration and H2S. We have observed an increase in DNMT1 and decreased FTO levels in the cortex of the brain of AD mice. Interestingly, we also observed that probiotic lactobacillus-producing post-biotic folate and lactone/ketone effectively prevented FOCM-associated gut dysbiosis and amyloid deposits. The s-adenosine-methionine (SAM) transporter (SLC25A) was increased by hyperhomocysteinemia (HHcy). Thus, we hypothesize that chronic gut dysbiosis induces SLC25A, the gene writer, and HHcy, and decreases the gene eraser, leading to a decrease in SLC7A and mitochondrial transsulfuration H2S production and bioenergetics. Lactobacillus engulfs lipids/cholesterol and a tri-directional post-biotic, folic acid (an antioxidant and inhibitor of beta amyloid deposits; reduces Hcy levels), and the lactate ketone body (fuel for mitochondria) producer increases SLC7A and H2S (an antioxidant, potent vasodilator and neurotransmitter gas) production and inhibits amyloid deposits. Therefore, it is important to discuss whether lactobacillus downregulates SLC25A and DNMT1 and upregulates TET2/FTO, inhibiting β-amyloid deposits by lowering homocysteine. It is also important to discuss whether lactobacillus upregulates SLC7A and inhibits β-amyloid deposits by increasing the mitochondrial transsulfuration of H2S production.