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Does intermittent fasting associated with aerobic training influence parameters related to the gut-brain axis of Wistar rats?
BACKGROUND: Intermittent fasting (IF) and aerobic training have demonstrated beneficial effects on intestinal microbiota composition, but little is known about benefits to the brain through the gut-brain axis. The present study aimed to evaluate gut-brain axis parameters in Wistar rats submitted to IF associated or not with aerobic training. METHODS: Male rats were evaluated for training performance and then randomized into 4 groups of ten: sedentary control (SC), trained control (TC), sedentary intermittent fasting (SIF), and trained intermittent fasting (TIF), and evaluated during four weeks. RESULTS: The adiposity index was similar among the TC (2.15±0.43%), SIF (1.98±0.69%) and TIF (1.86±0.51%) groups, and differed from SC (2.98±0.80%). TIF had lower counts of lactic acid bacteria, while SIF had higher counts of Bifidobacterium and Enterococcus. TIF had the highest amount of formic acid in faeces (44.44±2.40 μmol/g) and lowest amount of succinic acid in the gut (0.38±0.00 μmol/g), while SIF had the highest propionic acid amount in the faeces (802.80±00.33 μmol/g) and the lowest amount of lactic acid in the gut (0.85±0.00 μmol/g). TIF demonstrated a tendency towards an anxiolytic effect and SIF showed potential antidepressant effect. IF caused different brain and intestinal injuries. TIF rats presented a diffuse and intense marking of IL-1β in the hippocampus. CONCLUSION: IF and aerobic exercise, associated or not, can modulate parameters related to the gut-brain axis of Wistar rats, and some benefits may be related to the amounts of organic acids.
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Effects of Supplementation with Lactobacillus Probiotics on Insomnia Treatment.
CONTEXT: According to the criteria of the International Classification of Sleep Disorders (ICSD-3), it is estimated that the prevalence of insomnia in the general population varies between 6.6% and 12%. Insomnia is a sleep disturbance related to a reduction in the quality or quantity of satisfactory sleep. Among the available treatments, there are both pharmacological and non-pharmacological approaches. One recent possible non-pharmacological approach that has been suggested is based on the use of probiotics and the gut-brain axis. There has been increasing scientific focus on this area because of the suggested importance of enteric microbiota in relation to many aspects of health. It has been proposed that probiotics can be used to interact with the intestinal environment to benefit individuals suffering from a variety of conditions. In relation to sleep, some studies have indicated that gamma-amino butyric acid (GABA) produced by the intestinal microbiota may influence the central nervous system (CNS) through the vagus nerve and have an influence on sleep. In this sense, Lactobacillus is one of the major GABA producing bacteria in the gut microbiota. OBJECTIVE: Our hypothesis is that supplementation with Lactobacillus as a probiotic might improve sleep pattern and quality, acting as an ally in the treatment of insomnia. DESIGN: In the present study, a search was conducted in Pubmed and Google Scholar databases, looking for articles with themes related to probiotics, intestinal microbiota and sleep. RESULTS: No clinical trials were found that evaluated the effect of probiotics for sleep disorders in humans.Conclusions • Research and clinical use of probiotics have been growing due to their health benefits in several areas. In addition, the use of probiotics for sleep and emotional disorders, such as insomnia, stress, anxiety and depression, is gaining space. This way, future research can help developing complementary treatments for people with insomnia and other sleep disorders.
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Peripheral Immune-Inflammatory Pathways in Major Depressive Disorder, Bipolar Disorder, and Schizophrenia: Exploring Their Potential as Treatment Targets.
Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are major mental disorders linked to substantial morbidity. Traditional monoamine-based pharmacotherapies frequently produce inadequate outcomes for many patients. The elevated levels of treatment resistance require the exploration of new pharmacological targets. Evidence indicates that peripheral immune-inflammatory dysregulation, characterized by an imbalance between immunological responses and compensatory immune-regulatory systems (IRS/CIRS), together with increased oxidative and nitrosative stress (O&NS), significantly contributes to the pathogenesis of these disorders. This review examines IRS/CIRS/O&NS pathways as new drug targets and highlights novel pharmacological trials. Antiinflammatory drugs have been repurposed as augmentation strategies for the treatment of MDD/BD and SCZ, including nonsteroidal antiinflammatory medications, such as cyclooxygenase-2 (COX-2) inhibitors; cytokine-targeting biologics, such as tumor necrosis factor-α monoclonal antibodies; and minocycline, an antibiotic that attenuates neuroinflammation. N-acetylcysteine, curcumin, and omega-3 polyunsaturated fatty acids demonstrate some efficacy as augmentation therapies in MDD, likely by diminishing IRS activation and O&NS. Strategies aimed at the gut-brain axis and gut dysbiosis, including fecal microbiota transplantation, are under investigation for their capacity to restore immunological homeostasis by improving gut barrier integrity and microbiome composition. This review examines new potential therapeutic targets arising from recent discoveries in neuro-immune interactions and oxidative stress, including particular lymphocyte surface markers, the CIRS, and intracellular network molecules in both affective and psychotic disorders. The evidence underscores the clinical importance of immune-targeted augmentation treatments in psychiatric disorders and supports the ongoing development of these novel pharmacotherapies within a precision medicine paradigm.
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Squid-ink-derived eumelanin nanoparticles improve glycaemic control through gut-centered metabolic remodeling in type 2 diabetes.
Type 2 diabetes (T2D) is increasingly recognized as a systemic metabolic disorder in which intestinal dysfunction contributes to multi-organ metabolic imbalance. Here we show that orally administered squid-ink-derived eumelanin nanoparticles (EmNPs) ameliorate hyperglycaemia and tissue injury in diabetic mice. Structural analyses confirmed that EmNPs retain the characteristic indole/quinone framework, stable radical properties and nanoscale self-assembled architecture of natural eumelanin. In vivo, EmNPs lowered fasting blood glucose, improved an FST-based depression-related behavioral readout, and improved histopathological injury in the small intestine, pancreas and hippocampus. To investigate the basis of these effects, we integrated gut microbiota profiling, intestinal transcriptomics, untargeted urinary metabolomics and targeted hepatic energy-metabolite analysis. EmNPs treatment was associated with partial correction of diabetes-associated gut microbial dysbiosis and was accompanied by intestinal transcriptional remodeling centred on epithelial/barrier function, amino acid metabolism, PPAR-related pathways and bile-acid-associated programs. These intestinal changes were associated with broad correction of urinary metabolic abnormalities involving amino acid, purine and energy metabolism. Targeted hepatic metabolite profiling further revealed EmNPs-associated remodeling of glycolysis- and TCA-related steady-state metabolite abundance. Together, these findings support an association-based, gut-centered model in which changes in the intestinal metabolic milieu are associated with systemic metabolic normalization, hepatic energy-metabolite remodeling, and improved glycaemic control in T2D.
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New Insights into the oral microbiota and host epigenetic changes in obsessive compulsive disorder and major depressive disorder: Focus on BDNF.
Obsessive-Compulsive Disorder (OCD) and Major Depressive Disorder (MDD) frequently co-occur, with depressive symptoms affecting OCD progression and vice versa. Identifying biomarkers is crucial for improving diagnosis and treatment. While the gut microbiota's role in psychiatric disorders is well-studied, this research focuses on alterations in the oral microbiota and their relationship with BDNF (Brain-Derived Neurotrophic Factor) DNA methylation in OCD and MDD patients compared to healthy controls. Our findings reveal significant changes in microbiota composition with OCD patients showing increased Actinobacteriota and Firmicutes abundances (p < 0.05; CTRL = n.24, OCD = n.29), while MDD patients exhibiting increased Actinobacteriota and Firmicutes, with reduced Bacteroidota and Proteobacteria abundances (p < 0.05; CTRL = n.24, MDD = n.20). These alterations, including potential post-streptococcal autoimmunity, highlight the microbiota's role in OCD and MDD pathophysiology. Selective changes in BDNF DNA methylation were observed in both disorders at CpG sites in exon I and IV, significantly reduced in OCD and MDD (p < 0.05; CTRL = n.24, OCD = n.29, MDD = n.20) and, following miRNome analysis, showed altered expression of BDNF-targeting microRNAs, with miR-16-5p and miR-29a-3p upregulated in OCD (p < 0.05; CTRL = n.24, OCD = n.17), and miR-29a-3p upregulated and miR-191-5p downregulated in MDD (p < 0.05; CTRL = n.24, MDD = n.16). These findings suggest disorder-specific microbiota and epigenetic profiles, positioning saliva as a non-invasive tool for biomarker identification. This research advances the understanding of microbial-epigenetic interactions in OCD and MDD, potentially guiding early diagnosis and targeted therapies.
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Heavy Metal Interactions with Neuroglia and Gut Microbiota: Implications for Huntington's Disease.
Huntington's disease (HD) is a rare but progressive and devastating neurodegenerative disease characterized by involuntary movements, cognitive decline, executive dysfunction, and neuropsychiatric conditions such as anxiety and depression. It follows an autosomal dominant inheritance pattern. Thus, a child who has a parent with the mutated huntingtin (mHTT) gene has a 50% chance of developing the disease. Since the HTT protein is involved in many critical cellular processes, including neurogenesis, brain development, energy metabolism, transcriptional regulation, synaptic activity, vesicle trafficking, cell signaling, and autophagy, its aberrant aggregates lead to the disruption of numerous cellular pathways and neurodegeneration. Essential heavy metals are vital at low concentrations; however, at higher concentrations, they can exacerbate HD by disrupting glial-neuronal communication and/or causing dysbiosis (disturbance in the gut microbiota, GM), both of which can lead to neuroinflammation and further neurodegeneration. Here, we discuss in detail the interactions of iron, manganese, and copper with glial-neuron communication and GM and indicate how this knowledge may pave the way for the development of a new generation of disease-modifying therapies in HD.
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Intestinal permeability and gut microbiota interactions of pharmacologically active compounds in valerian and St. John's wort.
Phytomedicines such as valerian and St. John's wort are widely used for the treatment of sleeping disorders, anxiety and mild depression. They are perceived as safe alternatives to synthetic drugs, but limited information is available on the intestinal absorption and interaction with human intestinal microbiota of pharmacologically relevant constituents valerenic acid in valerian, and hyperforin and hypericin in St. John's wort. The intestinal permeability of these compounds and the antidepressant and anxiolytic drugs citalopram and diazepam was investigated in the Caco-2 cell model with bidirectional transport experiments. In addition, interaction of compounds and herbal extracts with intestinal microbiota was evaluated in artificial human gut microbiota. Microbiota-mediated metabolisation of compounds was assessed, and bacterial viability and short-chain fatty acids (SCFA) production were measured in the presence of compounds or herbal extracts. Valerenic acid and hyperforin were highly permeable in Caco-2 cell monolayers. Hypericin showed low-to-moderate permeability. An active transport process was potentially involved in the transfer of valerenic acid. Hyperforin and hypericin were mainly transported through passive transcellular diffusion. All compounds were not metabolized over 24 h in the artificial gut microbiota. Microbial SCFA production and bacterial viability was not substantially impaired nor promoted by exposure to the compounds or herbal extracts.
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ZiBuPiYin recipe improves cognitive decline by regulating gut microbiota in Zucker diabetic fatty rats.
Numerous researches supported that microbiota can influence behavior and modulate cognitive function through "microbiota-gut-brain" axis. Our previous study has demonstrated that ZiBuPiYin recipe (ZBPYR) possesses excellent pharmacological effects against diabetes-associated cognitive decline. To elucidate the role of ZBPYR in regulating the balance of gut microbiota to improve psychological-stress-induced diabetes-associated cognitive decline (PSDACD), we compared blood glucose, behavioral and cognitive functions and diversity of the bacterial community among experimental groups. The Zucker diabetic fatty (ZDF) rats with PSDACD exhibited behavioral and cognitive anomalies showing as increased anxiety- and depression-like behaviors and decreased learning and memory abilities. High-throughput sequencing of the bacterial 16S rRNA gene revealed that Roseburia and Coprococcus were decreased in ZDF rats with PSDACD compared with control group. Notably, these changes were reversed by ZBPYR treatment. Our findings indicate that ZBPYR might prevent PSDACD by maintaining the compositions of gut microbiota, which could be developed as a new therapy for T2D with PSDACD.
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Restoring an adequate dietary fiber intake by inulin supplementation: a pilot study showing an impact on gut microbiota and sociability in alcohol use disorder patients.
Alcohol use disorder (AUD) is a chronic relapsing disease associated with malnutrition, metabolic disturbances, and gut microbiota alterations that are correlated with the severity of psychological symptoms. This study aims at supplementing AUD patients with prebiotic fiber during alcohol withdrawal, in order to modulate the gut microbiota composition and to evaluate its effect on gastrointestinal tolerance, metabolism, and patient's behavior. A randomized, double-blind, placebo-controlled study included 50 AUD patients assigned to inulin versus maltodextrin daily supplementation for 17 days. Biological measurements (fecal microbial 16S rDNA sequencing, serum biology), dietary intake, validated psychological questionnaires, and gastrointestinal tolerance assessment were performed before and after the intervention. Inulin significantly decreased the richness and evenness and induced changes of 8 genera (q < 0.1) including Bifidobacterium and Bacteroides. Prebiotic had minor effects on gastrointestinal symptoms and nutritional intakes compared to placebo. All patients showed an improvement in depression, anxiety, and craving scores during alcohol withdrawal regardless of the intervention group. Interestingly, only patients treated with inulin significantly improved the sociability score and had an increased serum level of brain-derived neurotrophic factor. This pilot study shows that inulin is well tolerated and modulates the gut microbiota and the social behavior in AUD patients, without further improving other psychological and biological parameters as compared to placebo. Gut2Brain study, clinicaltrial.gov: NCT03803709, https://clinicaltrials.gov/ct2/show/NCT03803709.
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Exploring the acute and chronic effects of a multistrain probiotic supplement on cognitive function and mood in healthy older adults: a randomized controlled trial.
BACKGROUND: Aging is associated with a decline in cognitive function and vulnerability to depression. Probiotic supplements have shown beneficial effects on cognition and mood in clinical populations, but the potential benefit for healthy older adults experiencing age-related decline in cognition remains unclear. OBJECTIVES: The primary aim of the present work was to explore the effect of a chronic (long-term) multispecies probiotic intervention on cognition in healthy aging adults. Secondary aims included exploring the chronic effect on mood outcomes and gut microbiota community, as well as a novel investigation into the acute effect of supplementation on cognition and mood. METHODS: The study employed a randomized, placebo-controlled, cross-over trial in 30 healthy older adults to explore the acute (1 d) and chronic (8 wk) effects of a probiotic supplement on cognitive domains of memory and executive function, alongside mood measures of stress, anxiety, depression, and cognitive reactivity to sad mood. 16s rRNA sequencing of stool samples was also performed pre- and postchronic intervention to assess potential effects on the gut microbiota. RESULTS: Acute probiotic supplementation was associated with faster reaction times on cognitively demanding trials during a task of executive function [-64.91 ms, 95% confidence interval (CI): -115.70, -14.15]. Chronic supplementation was associated with improvement in cognitive biases such as hopelessness (-0.97, 95% CI: -1.72, -0.23), rumination (-1.58, 95% CI: -2.86, -0.29), and aggression (-1.57, 95% CI: -2.63, -0.51) that contribute to reactivity to sad mood and therefore vulnerability to depression, and may improve executive function under higher cognitive demand (0.43%, 95% CI: -0.53%, 1.38%). CONCLUSIONS: The current work provides novel evidence for an acute effect of probiotics on reaction times during executive function, which should be replicated in future work. Additionally, this work replicates previous findings of improved cognitive reactivity to sad mood following chronic probiotic supplementation, indicating probiotics may reduce risk of developing depression in a healthy aging population. This study was registered at clinicaltrials.gov as NCT04951687.