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Mechanical allodynia corresponds to Oprm1 downregulation within the descending pain network of male and female rats exposed to neonatal immune challenge.
Exposure to painful procedures and/or stressors during the early neonatal period can reprogram the underlying neurocircuitry involved in nociception and neuropathic pain perception. The reprogramming of these systems can result in an enduring elevation in sensitivity towards mechanical and thermal stimuli. Recent evidence suggests that exposure to mild inflammatory mediators during the neonatal period can induce similar pain responses in both adolescent and adult rats. Therefore, we sought to profile changes in the expression of several genes across brain areas involved in the active modulation of nociception and neuropathic pain using a well-recognized model of neonatal inflammation. In the present study male and female Sprague-Dawley rats were administered either the inflammatory endotoxin lipopolysaccharide (LPS; 0.05mg/kg, i.p.) or saline (equivolume) on postnatal days (PND) 3 and 5. During adolescence, hind paw mechanical withdrawal thresholds were evaluated using an electronic von Frey anesthesiometer. Animals challenged neonatally with LPS (nLPS) had increased pain sensitivity on this measure which was associated with decreased Oprm1 expression in the prefrontal cortex (PFC) and periaqueductal gray (PAG) of both male and female rats. Although a 'second hit' with LPS in adolescence (aLPS) did not confer protection or reveal additional vulnerabilities, aLPS given to animals treated neonatally with saline was associated with increased pain sensitivity, but only in females. Interestingly, adolescent inflammatory challenge decreased Hcrt2 mRNA in the PAG and elevated Trpv1 in the PAG and PFC of both sexes. There was no effect of inflammatory treatment on either anxiety or depressive-like behavior suggesting that affective functioning did not account for differences in mechanical pain sensitivity. Finally, a preliminary investigation demonstrated that administration of a broad spectrum antibiotic cocktail attenuated the mechanical sensitivity that followed nLPS. Together, these data extend upon evidence that inflammation imparts long term changes in quality of life and pain responses via interference within the descending pain network. Moreover, they highlight a potential window of opportunity to target the microbiota-gut-brain axis and reverse pain processing disturbances following perinatal inflammation.
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Intestinal barrier dysfunction in irritable bowel syndrome: a systematic review.
BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is a complex and heterogeneous disorder. Sensory, motor and barrier dysfunctions are the key physiological endophenotypes of IBS. Our aim is to review studies evaluating barrier dysfunction in adults and children with IBS, as well as to link those changes with IBS symptomatology and quality of life. METHODS: A comprehensive and systematic review of multiple databases was performed up to March 2020 to identify studies comparing intestinal permeability in IBS patients with healthy controls. Both in vivo and in vitro studies were considered. RESULTS: We identified 66 studies, of which 27 used intestinal probes to quantify barrier function. The prevalence of barrier dysfunction differed between PI-IBS (17-50%), IBS-D (37-62%) and IBS-C (4-25%). At a group level, permeability was increased compared with healthy controls in IBS-D (9/13 studies) and PI-IBS (4/4 studies), but only a minority of IBS-C (2/7 studies) and not in the only IBS-M study. All four studies in children with IBS demonstrated loss of barrier function. A heterogeneous set of tight junction genes were found to be altered in small and large intestines of adults with IBS, but these have not been evaluated in children. Positive associations were identified between barrier dysfunction and bowel disturbances (6/9 studies), abdominal pain (9/13 studies), overall symptom severity (1/6 studies), depression and anxiety (1/1 study) and quality of life (1/4 studies). Fecal slurry or supernatants of IBS patients were found to induce barrier disruption in animal models (5/6 studies). CONCLUSIONS: Barrier dysfunction is present in a significant proportion of adult and all pediatric IBS studies, especially in the IBS-D and PI-IBS subtype. The majority of studies indicated a positive association between loss of barrier function and symptoms such as abdominal pain and changes in the bowel function.
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Activity Engagement Across Stages of Cognitive Health.
Objective: This study aims to examine activity engagement across stages of cognitive health among older adults. Methods: We used a cross-sectional study analysis of baseline data collected as part of the prospective Microbiome in Aging of Gut and Brain (MiaGB) longitudinal study; the study period was August 2022 to December 2023. Health history and activity engagement questionnaires and the Montreal Cognitive Assessment (MoCA) were used to examine the study objective. One-way ANOVA and chi-squared tests, with Bonferroni post hoc analyses, assessed group differences. Results: The weighted samples reflected 417 participants: 54% females, 70.7% White, with an average age of 72 (±8.7) years, 90% with at least high school education, and 75% self-reported medium income status. Results suggested that individuals who scored ≤17 points on the MoCA had an average age of 84 years, were White, non-Hispanic, female, had less than a high school education, and medium income status (p < 0.001). Significant differences were found in active engagement in all health behaviors (p < 0.05). The frequency of engagement in activities was all statistically significant (p < 0.05), except the frequency of looking after grandchildren (p > 0.05). Older adults who scored ≤17 MoCA points reported higher rates of hypertension, osteoarthritis, and depression compared with individuals who scored higher on the MoCA assessment. Conclusions: Older adults with lower cognitive status report a higher rate of clinical ailments and have less engagement in meaningful activities. We should promote meaningful activities to improve the quality of life in older adults with decreased cognition. We make recommendations for appropriate modifications for activity engagement across cognitive health levels.
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Microbiome and ileum transcriptome revealed the boosting effects of selenium yeast on egg production in aged laying hens.
The declines in laying performance during the late production period have adverse effects on the length of the production cycle. Improving the nutrition of laying hens is a crucial measure to reverse this declination. This study investigated the effect of selenium yeast (SY) on egg production, ileal gene expression and microbiota, as well as elucidating their associations in aged laying hens. A total of 375 Jinghong laying hens at 76 weeks old were randomly assigned into 5 dietary treatments, which included a selenium-deficient basal diet based on corn-soybean meal, and dietary supplementation of SY at 0.15, 0.30 and 0.45 mg/kg, and sodium selenite at 0.45 mg/kg. The results showed that SY ameliorated the depression in aged laying performance in the 0.30 mg/kg group (P < 0.01). Selenium yeast significantly increased ileum selenium concentration (P < 0.05), and SY groups had higher selenium deposition efficiency than the sodium selenite group. Functional enrichment and Short Time-series Expression Miner (STEM) analysis indicated that SY activated metabolic progress (e.g., glycerolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism), immune response and oxidative stress response. Four hub genes including thioredoxin reductase 1 (TXNRD1), dihydrolipoamide dehydrogenase (DLD), integrin linked kinase (ILK) and leucine zipper tumor suppressor 2 (LZTS2) were involved in intestinal metabolism which was closely associated with selenium deposition/status. Moreover, the relative abundance of Veillonella, Turicibacter and Lactobacillus was significantly increased, but the relative abundance of Stenotrophomonas was significantly decreased by SY supplementation. Multi-omics data integration and Canonical correspondence analysis (CCA) showed that both the ileum selenium content and the laying rate were highly correlated with pathways and bacteria enriched in metabolism and immune response. Meanwhile, the "switched on" gene prostate stem cell antigen (PSCA) had a positive relationship with Veillonella and a negative relationship with the opportunistic pathogens Stenotrophomonas. Overall, our study offered insight for the further exploration of the role of SY on boosting egg production and balancing ileum intestinal flora in aged laying hens.
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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.