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Role of Hydroxytyrosol and Oleuropein in the Prevention of Aging and Related Disorders: Focus on Neurodegeneration, Skeletal Muscle Dysfunction and Gut Microbiota.
Aging is a multi-faceted process caused by the accumulation of cellular damage over time, associated with a gradual reduction of physiological activities in cells and organs. This degeneration results in a reduced ability to adapt to homeostasis perturbations and an increased incidence of illnesses such as cognitive decline, neurodegenerative and cardiovascular diseases, cancer, diabetes, and skeletal muscle pathologies. Key features of aging include a chronic low-grade inflammation state and a decrease of the autophagic process. The Mediterranean diet has been associated with longevity and ability to counteract the onset of age-related disorders. Extra virgin olive oil, a fundamental component of this diet, contains bioactive polyphenolic compounds as hydroxytyrosol (HTyr) and oleuropein (OLE), known for their antioxidant, anti-inflammatory, and neuroprotective properties. This review is focused on brain, skeletal muscle, and gut microbiota, as these systems are known to interact at several levels. After the description of the chemistry and pharmacokinetics of HTyr and OLE, we summarize studies reporting their effects in in vivo and in vitro models of neurodegenerative diseases of the central/peripheral nervous system, adult neurogenesis and depression, senescence and lifespan, and age-related skeletal muscle disorders, as well as their impact on the composition of the gut microbiota.
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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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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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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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Mechanisms and Methods to Understand Depressive Symptoms.
Depressive symptoms, feelings of sadness, anger, and loss that interfere with a person's daily life, are prevalent health concerns across populations that significantly result in adverse health outcomes with direct and indirect economic burdens at a national and global level. This article aims to synthesize known mechanisms of depressive symptoms and the established and emerging methodologies used to understand depressive symptoms; implications and directions for future nursing research are discussed. A comprehensive search was performed by Cumulative Index to Nursing and Allied Health Literature, MEDLINE, and PUBMED databases between 2000-2021 to examine contributing factors of depressive symptoms. Many environmental, psychological, and physiological factors are associated with the development or increased severity of depressive symptoms (anhedonia, fatigue, sleep and appetite disturbances to depressed mood). This paper discusses biological and psychological theories that guide our understanding of depressive symptoms, as well as known biomarkers (gut microbiome, specific genes, multi-cytokine, and hormones) and established and emerging methods. Disruptions within the nervous system, hormonal and neurotransmitters levels, brain structure, gut-brain axis, leaky-gut syndrome, immune and inflammatory process, and genetic variations are significant mediating mechanisms in depressive symptomology. Nursing research and practice are at the forefront of furthering depressive symptoms' mechanisms and methods. Utilizing advanced technology and measurement tools (big data, machine learning/artificial intelligence, and multi-omic approaches) can provide insight into the psychological and biological mechanisms leading to effective intervention development. Thus, understanding depressive symptomology provides a pathway to improve patients' health outcomes, leading to reduced morbidity and mortality and the overall nation-wide economic burden.Supplemental data for this article is available online at https://doi.org/10.1080/01612840.2021.1998261 .
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Comprehensive Management of Ulcerative Colitis and its Associated Intra-Extra Intestinal Complications with a Multifunctional Inulin Hydrogel Complex.
Excessive accumulation of reactive oxygen species (ROS) and dysbiosis of gut microbiota are pivotal etiological factors in the pathogenesis of ulcerative colitis (UC) and its associated intestinal and extraintestinal manifestations (e.g., intestinal microthrombosis, anxiety, and depression symptoms). This investigation presents a multifunctional inulin complex (PB/NKase@Inulin gel) incorporating Prussian blue nanozymes (PB NZs) and the thrombolytic agent nattokinase (NKase) for the therapeutic management of dextran sulfate sodium (DSS)-induced UC and its associated intestinal and extraintestinal complications. Following oral administration, the PB/NKase@Inulin gel, characterized by prolonged retention of PB NZs and NKase at inflamed colonic sites, can facilitate continuously ROS scavenging, attenuate oxidative stress damage, effectively reduce pro-inflammatory cytokine levels. Importantly, PB/NKase@Inulin gel can not only robustly inhibit inflammatory microthrombosis formation but also effectively lyses thrombi due to the potent thrombolytic properties of NKase both in vitro and in vivo. Furthermore, the PB/NKase@Inulin gel is able to modulate gut microbiota homeostasis and alleviate multiple stresses responses (including anxiety and depression) in a UC mouse model via microbiota-gut-brain (MGB) axis interactions. Overall, the PB/NKase@Inulin gel offers an innovative paradigm for comprehensive therapeutic interventions in DSS-induced UC and its multifaceted complications.