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Sodium Butyrate ameliorates pain and mood disorders in a mouse model of Parkinson disease.
Pain is one of non-motor features of Parkinson's disease (PD) that significantly impacts on patients' quality of life and increases the risk of developing psychiatric disorders. The mechanisms underlying pain in PD are poorly understood and the classic pharmacological treatments supplying to dopamine depletion have limited therapeutic effects on this symptom. It has been demonstrated that short chain fatty acids (SCFAs) play a key role in several central nervous system diseases including PD; low serum and faecal levels of SCFAs have been described in PD patients. Among SCFAs, the gut microbial metabolite butyrate has a neuroprotective and anti-inflammatory effect, influencing neurological and behavioural processes. Using a 6-hydroxydopamine (6-OHDA) induced-PD mouse model, we evaluated the effects of sodium butyrate (BuNa) treatment on pain and mood-related behaviour, exporing the role of PPARs, opioid and endocannabinoid systems. Our results demonstrated that repeated BuNa treatment (100 mg/kg po) in PD-mice reduced pain hypersensitivity as well as depressive- and anxiety-lke behaviour both on day 7 and day 14 after 6-OHDA injection. Moreover, AM281(CB1R antagonist), GW6471 (PPAR-alpha antagonist), and naloxone (opioid receptor antagonist), reduced BuNa efficacy. Finally, BuNa treatment was associated with a significant reduction of pro-inflammatory cytokines at spinal and supraspinal levels. In conclusion, our results demonstrate that increasing endogenous butyrate concentration reduces PD comorbidities such as pain and psychiatric symptoms, restoring opioidergic and endocannabinergic pathways.
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Long COVID Symptom Management Through Self-Care and Nonprescription Treatment Options: A Narrative Review.
Many patients experience unique or persistent symptoms several months following the onset of infection with severe acute respiratory syndrome coronavirus 2, the causative agent of COVID-19. While this condition is commonly referred to as long COVID, no universally accepted definition exists; therefore, many patients go underrecognized and underreported. Long COVID can involve almost any major organ system and is characterized by widely heterogeneous persistent or recurrent symptoms including fatigue, headache, cough, dyspnea, chest pain, cognitive dysfunction, anxiety, and depression. In line with the wide array of symptoms, numerous potential underlying pathophysiologic pathways, including viral persistence, prolonged inflammation, autoimmune reactions, endothelial dysfunction, and dysbiosis of the microbiome of the gut, may contribute to the symptomology of long COVID. Therapy is directed at symptomatic control; however, no pharmacologic treatments are specifically approved for the management of symptoms associated with long COVID. Several common symptoms of long COVID may be managed with nonprescription treatments (pharmacologic and nonpharmacologic). The goal of this review is to provide clinicians with a better understanding of long COVID and review the latest recommendations for managing common mild-to-moderate symptoms with nonprescription treatment options.
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Transcutaneous auricular vagus nerve stimulation as a potential novel treatment for polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of childbearing age. The etiology of PCOS is multifactorial, and current treatments for PCOS are far from satisfactory. Recently, an imbalanced autonomic nervous system (ANS) with sympathetic hyperactivity and reduced parasympathetic nerve activity (vagal tone) has aroused increasing attention in the pathogenesis of PCOS. In this paper, we review an innovative therapy for the treatment of PCOS and related co-morbidities by targeting parasympathetic modulation based on non-invasive transcutaneous auricular vagal nerve stimulation (ta-VNS). In this work, we present the role of the ANS in the development of PCOS and describe a large number of experimental and clinical reports that support the favorable effects of VNS/ta-VNS in treating a variety of symptoms, including obesity, insulin resistance, type 2 diabetes mellitus, inflammation, microbiome dysregulation, cardiovascular disease, and depression, all of which are also commonly present in PCOS patients. We propose a model focusing on ta-VNS that may treat PCOS by (1) regulating energy metabolism via bidirectional vagal signaling; (2) reversing insulin resistance via its antidiabetic effect; (3) activating anti-inflammatory pathways; (4) restoring homeostasis of the microbiota-gut-brain axis; (5) restoring the sympatho-vagal balance to improve CVD outcomes; (6) and modulating mental disorders. ta-VNS is a safe clinical procedure and it might be a promising new treatment approach for PCOS, or at least a supplementary treatment for current therapeutics.
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Diabetes mellitus is an independent risk factor for a greater frequency of early satiation and diarrhea at one and three years: Two prospective longitudinal population-based studies.
BACKGROUND: Psychological and lifestyle factors have been associated with gastrointestinal (GI) symptoms in individuals with diabetes mellitus, but it remains unclear whether they explain the relationship over time. We aimed to determine in two independent population-based studies whether diabetes is an independent risk factor for GI symptoms at a 1- and 3-year follow-up, adjusting for these factors. METHODS: In study 1, 1900 individuals completed a baseline and 1-year follow-up survey, while in study 2, 1322 individuals completed a baseline and 3-year follow-up survey. Both studies asked about self-reported diagnoses of diabetes and GI symptoms over the previous 3 months. Psychological, lifestyle factors (body mass index [BMI], smoking) and age and sex were assessed. KEY RESULTS: The baseline prevalence of diabetes was 7.8% in Survey 1 and 8.9% in Survey 2. In a multivariate model that included age, sex, BMI, anxiety, depression and smoking status at follow-up, reporting diabetes at baseline was an independent predictor of at least weekly early satiation (OR 1.58, 95% CI 1.05, 2.39, p = 0.03; OR = 1.67, 95% CI 1.14, 2.45, p = 0.009), fecal urgency (OR 1.44,95% CI 1.06, 1.95, p = 0.02; OR = 2.17, 95% CI 1.47, 3.22, p = 0.0001), > 3 bowel motions a day (OR 1.50, 95% CI 1.08, 2.07, p = 0.02; OR = 1.67, 95% CI 1.11, 2.51, p = 0.01), and loose stools (OR 1.40, 95% CI 1.04, 1.90, p = 0.03; OR = 1.68, 95% CI 1.13, 2.51, p = 0.01) at the 1- and 3-year follow-ups, respectively. CONCLUSIONS & INFERENCES: Diabetes is an independent risk factor for a greater frequency of early satiation and diarrhea, adjusting for lifestyle and psychological factors.
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Life style and interaction with microbiota in prostate cancer patients undergoing radiotherapy: study protocol for a randomized controlled trial.
BACKGROUND: Prostate cancer (PCa) is the second most common cancer in men worldwide. The standard non-surgical approach for localized PCa is radiotherapy (RT), but one of the limitations of high-dose RT is the potential increase in gastrointestinal and genitourinary toxicities. We present the protocol of the Microstyle study, a multicentre randomized two-arm crossover clinical trial. The primary outcome will be assessed at the end of 6-month intervention, by measuring the change in adherence to a healthy lifestyle score. The hypothesis is that modifying lifestyle we change microbiome and improve quality of life and decrease side effects of RT. METHODS: Study participants will be recruited among men undergoing RT in two Italian centers (Milan and Naples). We foresee to randomize 300 patients in two intervention arms: Intervention Group (IG) and Control Group (CG). Participants allocated to the IG will meet a dietitian and a physiotherapist before RT to receive personalized diet and exercise recommendations, according to their health status, to improve overall lifestyle and reduce side effects (bowel and/or urinary problems). Dietitian and physiotherapist will work together to set individualized goals to reduce or eliminate side effects and pain according to their health status. All participants (IG) will be given a pedometer device (steps counter) in order to monitor and to spur participants to increase physical activity and reduce sedentary behavior. Participants included in the CG will receive baseline general advice and materials available for patients undergoing RT. According to the cross-over design, the CG will cross to the intervention approach after 6-month, to actively enhance compliance towards suggested lifestyle recommendations for all patients. DISCUSSION: This trial is innovative in its design because we propose a lifestyle intervention during RT, that includes both dietary and physical activity counselling, as well as monitoring changes in microbiome and serum biomarkers. The promotion of healthy behaviour will be initiated before initiation of standard care, to achieve long lasting effects, controlling side effects, coping with feelings of anxiety and depression and improve efficacy of RT. TRIAL REGISTRATION: ClincalTrial.gov registration number: NCT05155618 . Retrospectively registered on December 13, 2021. The first patient was enrolled on October 22, 2021.
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Traditional plant use during lactation and postpartum recovery: Infant development and maternal health roles.
ETHNOPHARMACOLOGICAL RELEVANCE: Evidence of phytochemical roles in infant development and maternal recovery offers insights into beneficial functions of traditional plant use during lactation and the postpartum period. Ethnopharmacological research has relevance to global priorities on maternal and child health, to understanding origins and determinants of human self-medication, and for reconciling traditional postpartum practices and mainstream healthcare. AIM OF THE STUDY: Present emerging evidence, within evolutionary and socio-cultural contexts, on the role of maternal consumption on transfer of phytochemicals into breast milk with impacts on maternal and child health, and on infant development. Establish current state of knowledge and an ethnopharmacological research agenda that is attentive to cross-cultural and regional differences in postpartum plant use. MATERIALS AND METHODS: An extensive literature review using Medline, Scopus, and Web of Science focused on traditional and contemporary use and socio-cultural context, as well as physiological, pharmacological, toxicological, and behavioral activities of plants used medicinally by women during postpartum recovery and lactation. RESULTS: The most widely reported postpartum plants show antimicrobial, anti-inflammatory, immunological, and neurophysiological activities, with low toxicity. Phytochemicals transfer from maternal consumption into breast milk in physiological concentrations, while animal studies demonstrate immunomodulation and other actions of medicinal plants during lactation. Reporting on the use and diverse traditional knowledge of women about plants during the postpartum period is obscured by the marginal place of obstetric issues and by gender biases in ethnobotanical research. In many contemporary contexts use is prejudiced by precautionary risk warnings in health literature and practice that confound lactation with pregnancy. CONCLUSIONS: Although systematic investigation of postpartum plant use is lacking, known pharmacological activities support potential benefits on infant development and maternal health with immediate and long-term consequences in relation to allergic, inflammatory, autoimmune, and other diseases. An ethnopharmacological agenda focused on the perinatal period requires directed methodologies and a regional approach in relation to culturally-specific knowledge and practices, traditional plant use, and local health needs. Testing the hypothesis that phytochemicals transferred from medicinal plants into breast milk impact the human immune system and other aspects of infant development requires extended analysis of phytochemicals in human milk and infant lumen and plasma, as well as effects on gastrointestinal and milk microbiome.
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Dectin-1 signaling on colonic γδ T cells promotes psychosocial stress responses.
The intestinal immune system interacts with commensal microbiota to maintain gut homeostasis. Furthermore, stress alters the microbiome composition, leading to impaired brain function; yet how the intestinal immune system mediates these effects remains elusive. Here we report that colonic γδ T cells modulate behavioral vulnerability to chronic social stress via dectin-1 signaling. We show that reduction in specific Lactobacillus species, which are involved in T cell differentiation to protect the host immune system, contributes to stress-induced social-avoidance behavior, consistent with our observations in patients with depression. Stress-susceptible behaviors derive from increased differentiation in colonic interleukin (IL)-17-producing γδ T cells (γδ17 T cells) and their meningeal accumulation. These stress-susceptible cellular and behavioral phenotypes are causally mediated by dectin-1, an innate immune receptor expressed in γδ T cells. Our results highlight the previously unrecognized role of intestinal γδ17 T cells in the modulation of psychological stress responses and the importance of dectin-1 as a potential therapeutic target for the treatment of stress-induced behaviors.
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NOD-like receptors mediate homeostatic intestinal epithelial barrier function: promising therapeutic targets for inflammatory bowel disease.
Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disease that involves host genetics, the microbiome, and inflammatory responses. The current consensus is that the disruption of the intestinal mucosal barrier is the core pathogenesis of IBD, including intestinal microbial factors, abnormal immune responses, and impaired intestinal mucosal barrier. Cumulative data show that nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are dominant mediators in maintaining the homeostasis of the intestinal mucosal barrier, which play critical roles in sensing the commensal microbiota, maintaining homeostasis, and regulating intestinal inflammation. Blocking NLRs inflammasome activation by botanicals may be a promising way to prevent IBD progression. In this review, we systematically introduce the multiple roles of NLRs in regulating intestinal mucosal barrier homeostasis and focus on summarizing the activities and potential mechanisms of natural products against IBD. Aiming to propose new directions on the pathogenesis and precise treatment of IBD.
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Non-Helicobacter pylori Helicobacters, a Treatable Provocateur of Parkinson's Disease: Hypothesis, Evidence and Species Specificity.
Epidemiological and eradication trial evidence indicates that Helicobacter pylori, a major causative factor in peptic ulcer and gastric cancer, is a driver of the hypokinesia of Parkinson's disease (PD). Psychological (cognitive impairment, depression and anxiety) and gastrointestinal (peptic ulceration and constipation) PD features can precede the symptomatic onset of motor features by decades. We hypothesise that the non-H. pylori Helicobacters (NHPH), which have farm, companion and wild animals as their main hosts, can have a role in PD aetiopathogenesis. In those occupationally at risk of NHPH infection, we address whether there is increased mortality with PD, or depression or suicide. Our systematic review gave evidence that occupational exposure to animals/their products is associated with excess mortality with PD. Indeed, whilst livestock farming increased the risk, crop farming decreased it. Moreover, excess mortality from non-Hodgkin lymphoma in livestock farmers is compatible with NHPH being causal. Our scoping review showed that farmers, veterinarians and abattoir workers have an increased risk of depression and suicide; whether their depression is associated with being down the pathway to PD and/or the presence of Helicobacter infection needs investigation. Regarding Helicobacter species specificity, the link between the presence of NHPH in gastric biopsy and PD was described using a ureA polymerase chain reaction (PCR) assay, targeting the most-commonly named NHPH, H. suis. We describe its redesign and optimisation as a probe-based PCR, confirming the exclusion of H. pylori but not H. suis specificity (additionally identifying 6 species of a 22-NHPH-species panel). The exploration of the zoonotic hypothesis requires a non-invasive pan-Helicobacter PCR screen, allowing the detection and molecular grouping of Helicobacter species.
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Dynamic effects of black soldier fly larvae meal on the cecal bacterial microbiota and prevalence of selected antimicrobial resistant determinants in broiler chickens.
BACKGROUND: We had earlier described the growth-promoting and -depressive effects of replacing soybean meal (SBM) with low (12.5% and 25%) and high (50% and 100%) inclusion levels of black soldier fly larvae meal (BSFLM), respectively, in Ross x Ross 708 broiler chicken diets. Herein, using 16S rRNA gene amplicon sequencing, we investigated the effects of replacing SBM with increasing inclusion levels (0-100%) of BSFLM in broiler diets on the cecal bacterial community composition at each growth phase compared to broilers fed a basal corn-SBM diet with or without the in-feed antibiotic, bacitracin methylene disalicylate (BMD). We also evaluated the impact of low (12.5% and 25%) inclusion levels of BSFLM (LIL-BSFLM) on the prevalence of selected antimicrobial resistance genes (ARGs) in litter and cecal samples from 35-day-old birds. RESULTS: Compared to a conventional SBM-based broiler chicken diet, high (50 to100%) inclusion levels of BSFLM (HIL-BSFLM) significantly altered the cecal bacterial composition and structure, whereas LIL-BSFLM had a minimal effect. Differential abundance analysis further revealed that the ceca of birds fed 100% BSFLM consistently harbored a ~ 3 log-fold higher abundance of Romboutsia and a ~ 2 log-fold lower abundance of Shuttleworthia relative to those fed a BMD-supplemented control diet at all growth phases. Transient changes in the abundance of several potentially significant bacterial genera, primarily belonging to the class Clostridia, were also observed for birds fed HIL-BSFLM. At the finisher phase, Enterococci bacteria were enriched in the ceca of chickens raised without antibiotic, regardless of the level of dietary BSFLM. Additionally, bacitracin (bcrR) and macrolide (ermB) resistance genes were found to be less abundant in the ceca of chickens fed antibiotic-free diets, including either a corn-SBM or LIL-BSFLM diet. CONCLUSIONS: Chickens fed a HIL-BSFLM presented with an imbalanced gut bacterial microbiota profile, which may be linked to the previously reported growth-depressing effects of a BSFLM diet. In contrast, LIL-BSFLM had a minimal effect on the composition of the cecal bacterial microbiota and did not enrich for selected ARGs. Thus, substitution of SBM with low levels of BSFLM in broiler diets could be a promising alternative to the antibiotic growth promoter, BMD, with the added-value of not enriching for bacitracin- and macrolide-associated ARGs.