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Multisensory Fusion Training and 7, 8-Dihydroxyflavone Improve Amyloid-β-Induced Cognitive Impairment, Anxiety, and Depression-Like Behavior in Mice Through Multiple Mechanisms.
BACKGROUND: There is growing interest in the role of physical activity in patients with of Alzheimer's disease (AD), particularly regarding its impact of cognitive function, gut microbiota, metabolites, and neurotrophic factors. OBJECTIVE: To investigate the impact of multisensory fusion training (MSFT) combined with 7, 8-dihydroxyflavone (DHF) on the behavioral characteristics, protein expression, microbiome, and serum metabolome using the AD model in mice induced with amyloid-β (Aβ). METHODS: We assessed cognitive ability, anxiety-like and depression-like behaviors in Aβ mice using behavioral measures. Western blotting was employed to detect the expression of relevant proteins. The 16S rRNA gene sequencing and metabolomics were used to analyze changes in the intestinal microbial composition and serum metabolic profile, respectively, of Aβ mice. RESULTS: The behavioral outcomes indicated that a 4-week intervention combining DHF and MSFT yielded remarkable improvements in cognitive function and reduced anxiety and depression-like behaviors in Aβ mice. In the hippocampus of Aβ mice, the combined intervention increased the levels of BDNF, VGF, PSD-95, Nrf2, p-GSK3β and p-CREB proteins. Analyses of sequence and metabolomic data revealed that Bacteroides and Ruminococcaceae were remarkably more abundant following the combined intervention, influencing the expression of specific metabolites directly linked to the maintenance of neuronal and neurobehavioral functions. These metabolites play a crucial role in vital processes, such as amino acid metabolism, lipid metabolism, and neurotransmitter metabolism in mice. CONCLUSION: Our study highlighted that MSFT combined with DHF improves cognitive impairment, anxiety, and depression-like behavior in Aβ mice through multiple mechanisms, and further validated the correlation between the gut microbiome and serum metabolome. These findings open up a promising avenue for future investigations into potential treatment strategies for AD.
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The anti-depressive role of the Pei Yuan Kai Yu formula in cerebral small vessel disease based on gut microbiota.
BACKGROUND: Cerebral small vessel disease (CSVD), characterized by pathological changes in brain vessels, is a common cause of death in the elderly and often accompanied by depression, which significantly affects patients' quality of life and rehabilitation; understanding its pathogenesis and developing innovative therapies are urgently needed, especially considering the role of the blood - brain barrier impairment and the gut - microbiota - gut - brain axis in this complex condition. METHODS: Dahl/SS rats were fed a diet containing 8% NaCl and were subjected to chronic unpredictable mild stress (CUMS) stimulation for 4 weeks. PY (1.407 g/kg/day) was administered intragastrically to evaluate its role in CSVD with depression. Pseudo germ-free rats were colonized with gut microbiota from high-salt-fed rats exposed to CUMS, followed by PY administration. RESULTS: In rats with CSVD and depression, PY significantly increased body weight; alleviated depression-like behaviors; and decreased the levels of inflammatory cytokines such as TNF-α, IL-1β, and IL-6 in both serum and hippocampus. Additionally, PY reversed inflammation-induced nerve damage; reduced the overexpression of microglia in the hippocampus; decreased the levels of hippocampal VEGF and MMP-9, and increased the levels of hippocampal occludin, ZO-1, and claudin-5. Moreover, PY improved the composition of gut microbiota and enhanced microbial diversity. PY induced characteristic changes in the microbiome, which were associated with inflammation, endothelial dysfunction, and depressive-like behaviors. These significant metabolites were identified and were found closely related to inflammation, endothelial cell dysfunction, and depression-like behaviors. CONCLUSION: In conclusion, PY acts as an antidepressant to slow down the progression of CSVD by inhibiting microglial activation, reducing inflammation and ameliorating endothelial dysfunction. It exerts its effect, at least in part, by enhancing microbiota-mediated metabolism in vivo.
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Methodological and conceptual complexities of assessing relationships between single-occasion CRP inflammation and daily affect.
Inflammation is commonly implicated in sustained levels of depressed mood, chiefly with concurrent measures. There is a dearth of research on understanding how mood-inflammation relationships change on a day-to-day timescale. Determining how inflammation and mood may fluctuate and interact with each other is imperative to determining which pathways may lead to a depressed mood due to inflammation, and, more broadly, which factors induce inflammation in the first place. Therefore, we explored a means of elucidating the nature of mood-inflammation relationships using daily measures of mood and a single time-point measure of inflammation, C-Reactive Protein (CRP). We predicted that the relationship between affect and this measure of inflammation would be time-invariant because of evidence suggesting factors contributing to inflammation are persistent over time, such as obesity or poor gut-microbiome health. Our sample consisted of 1397 young adult participants who completed daily surveys for thirteen days and provided a blood sample for CRP measurement once at the conclusion of the study. A Bayesian multivariate regression model was performed to determine how daily levels of positive and negative mood could be predicted by this single time-point measure of inflammation. As part of our analysis, we sought to control for two key moderators, BMI and physical activity. Results indicated that moderate levels of inflammation were not associated with poor mood when the individual exercised. We also determined that high BMI participants exhibited a greater impact of inflammation on their mood relative to low BMI participants. However, contrary to our primary prediction that this mood-inflammation relationship would be time-invariant, we did indeed find that the relationship was time-variant. This result indicated that research examining associations involving inflammation daily will be required to understand which causative factors may contribute to fluctuations of a mood-inflammation relationship on a daily basis.
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Impact of Positive Glucose, Lactose, and Fructose Hydrogen Breath Tests on Symptoms and Quality of Life in Irritable Bowel Syndrome.
BACKGROUND: Gas production due to fermentation from fructose malabsorption (FM) or lactose malabsorption (LM) and small intestinal bacterial overgrowth (SIBO) contribute to the development of gastrointestinal symptoms in patients with irritable bowel syndrome (IBS). However, the impact of the carbohydrate malabsorption, unlike SIBO, is relatively unknown. METHODOLOGY: A multicenter, prospective study of consecutive adults with IBS who underwent a hydrogen breath test (HBT) (glucose, 75 g; lactose, 25 g; or fructose, 25 g) was conducted. The proportion of patients who tested positive for glucose, fructose and lactose HBT were evaluated. The symptom severity, psychology, and quality of life of subjects with SIBO were compared with those having LM and/or FM. Independent factors associated with severe IBS (IBS-symptom severity scale: IBS-SSS > 300) were explored. RESULTS: A total of 116 subjects were included (median age 56 years, male 35.3%). Of these, 23.3% (27/116), 85.7% (24/28), and 44.4% (16/36) of them tested positive for glucose, lactose, and fructose HBT, respectively. Among those with a positive HBT (n = 65), patients with SIBO were more likely to have the diarrhea-predominant subtype of IBS (77.8% vs. 47.4%, p = 0.014). Severe IBS was associated with SIBO, compared with LM/FM (SIBO: 36.4% vs. LM: 9.1%/FM 13.3%, p = 0.016). With multivariate analysis, SIBO (OR 5.25, p = 0.028) and depression (OR 5.59, p = 0.030) were independently associated with severe IBS. CONCLUSION: Although LM and FM commonly co-exist in IBS, their clinical relevance appears to be less significant than that of SIBO. The connection between SIBO with depression reinforces the importance of the microbiome-gut-brain axis in IBS.
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Decoding the gut-sleep Nexus: a bibliometric mapping of gut microbiota and sleep disorders.
BACKGROUND: An increasing number of studies have focused on the interaction between gut microbiota and sleep disorders. However, there is currently no bibliometric analysis of the literature on gut microbiota and sleep disorders. This study employs bibliometric methods to analyze the current research status and hotspots in the field of gut microbiota and sleep disorders, providing a reference for future research in this area. METHODS: Articles related to gut microbiota and sleep disorders were retrieved from the WOS core database, covering the period from the database's inception to December 31, 2024. After rigorous screening, VOSviewer and CiteSpace were used to conduct analyses on quantity, collaboration networks, clustering, and citation bursts. RESULTS: The number of articles on gut microbiota and sleep disorders has increased annually, with a significant surge after 2022. China has the highest number of publications, while the United States has the highest citation count. The institution with the most publications is Shanghai Jiao Tong University, and the institution with the most citations is Deakin University. The top 10 journals by publication volume are all ranked above Q2 in the JCR. The most cited article is "Gut microbiome diversity is associated with sleep physiology in humans" by Smith et al., published in PLOS ONE in 2019. The top 10 most frequent keywords are gut microbiota, sleep, depression, inflammation, chain fatty acids, anxiety, brain, oxidative stress, obesity, and health. The keyword cluster "obstructive sleep apnea" is a focal research direction, while fecal microbiota transplantation is a current research hotspot. CONCLUSION: This study reveals the publication trends, collaboration relationships among countries, regions, and authors, and recent research hotspots in the field of gut microbiota and sleep disorders through bibliometric methods, providing an objective data reference for scientific research in this domain.
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Microbiota and probiotics: chances and challenges - a symposium report.
The 10th International Yakult Symposium was held in Milan, Italy, on 13-14 October 2022. Two keynote lectures covered the crewed journey to space and its implications for the human microbiome, and how current regulatory systems can be adapted and updated to ensure the safety of microorganisms used as probiotics or food processing ingredients. The remaining lectures were split into sections entitled "Chances" and "Challenges." The "Chances" section explored opportunities for the science of probiotics and fermented foods to contribute to diverse areas of health such as irritable bowel syndrome, major depression, Parkinson's disease, immune dysfunction, infant colic, intensive care, respiratory infections, and promoting healthy longevity. The "Challenges" section included selecting appropriate clinical trial participants and methodologies to minimise heterogeneity in responses, how to view probiotics in the context of One Health, adapting regulatory frameworks, and understanding how substances of bacterial origin can cross the blood-brain barrier. The symposium provided evidence from cutting-edge research that gut eubiosis is vital for human health and, like space, the microbiota deserves further exploration of its vast potential.
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Fecal Microbiome in Women With Fibromyalgia: Functional Composition and Symptom Correlations.
OBJECTIVE: To describe the composition of the gut microbiota of women living with fibromyalgia, compared with controls, and examine the relationship between fecal microbiota and clinical features of fibromyalgia. METHODS: New Zealand women meeting American College of Rheumatology fibromyalgia criteria and age-matched controls provided fecal samples and completed validated surveys assessing pain, disorders of gut-brain interaction (DGBI), headaches, sleep quality, oral health, cognition, anxiety, depression, diet, and quality of life. Metatranscriptomic analysis identified phyla, genera, and species in fecal samples. Correlation coefficients were calculated for each α-diversity metric against clinical variables. Welch's t-test or Wilcoxon rank test was applied for binary clinical variables. Generalized linear models analyzed associations in the fibromyalgia group, adjusting for age, body mass index, and diet. Data processing and analysis used R version 4.2.1, with the Benjamini-Hochberg formula controlling for false discovery rate at ≤0.10 to minimize type 1 error risk. RESULTS: No statistically significant differences were seen in the microbial expression in fecal samples of women with fibromyalgia (n = 104) compared with controls (n = 52). Significant associations among three species from the Bacteroidetes phylum and cognitive impairment were observed. Fusobacteriota was significantly associated with Rome IV(B) DGBI, specifically epigastric pain syndrome. A strong association was observed between oral microbiota in feces and upper gastrointestinal DGBI, indicating both negative and positive correlations in this population. CONCLUSION: No overall differences in fecal microbial expression were found in women with fibromyalgia. However, Bacteroidetes and Fusobacteriota phyla were significantly associated with cognitive impairment and epigastric pain syndrome, respectively.
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Negative correlation between IL-1β, IL-12 and TNF-γ, and cortisol levels in patients with panic disorder.
INTRODUCTION: Chronic exposure to stress is a major risk factor in anxiety disorders (ADs) and can be accompanied by an altered microbiome-gut-brain axis and a compromised immune system. In recent years, the study of inflammatory processes in AD has gained special attention. Continued stress causes the reactivity of the hypothalamic-pituitary-adrenal (HPA) axis, the alteration of the intestinal microbiota and the consequent release of pro-inflammatory cytokines, affecting the sensitivity to stress and the similar behavior of anxiety. METHOD: The aim of the present study was to evaluate the interrelationships between measures of proinflammatory cytokines and cortisol in patients with panic disorder (PD). RESULTS: The main results of the correlation analysis revealed that the levels of pro-inflammatory cytokines interleukin (IL)-1β, IL-12, and tumor necrosis factor gamma were negatively correlated with cortisol scores (area under the curve with respect to the ground). CONCLUSIONS: These results suggest that the inflammatory response is associated with the reactivity of the HPA axis in patients with PD and may influence the maintenance of anxiety behavior.
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Intestinal metabolites predict treatment resistance of patients with depression and anxiety.
BACKGROUND: The impact of the gut microbiota on neuropsychiatric disorders has gained much attention in recent years; however, comprehensive data on the relationship between the gut microbiome and its metabolites and resistance to treatment for depression and anxiety is lacking. Here, we investigated intestinal metabolites in patients with depression and anxiety disorders, and their possible roles in treatment resistance. RESULTS: We analyzed fecal metabolites and microbiomes in 34 participants with depression and anxiety disorders. Fecal samples were obtained three times for each participant during the treatment. Propensity score matching led us to analyze data from nine treatment responders and nine non-responders, and the results were validated in the residual sample sets. Using elastic net regression analysis, we identified several metabolites, including N-ε-acetyllysine; baseline levels of the former were low in responders (AUC = 0.86; 95% confidence interval, 0.69-1). In addition, fecal levels of N-ε-acetyllysine were negatively associated with the abundance of Odoribacter. N-ε-acetyllysine levels increased as symptoms improved with treatment. CONCLUSION: Fecal N-ε-acetyllysine levels before treatment may be a predictive biomarker of treatment-refractory depression and anxiety. Odoribacter may play a role in the homeostasis of intestinal L-lysine levels. More attention should be paid to the importance of L-lysine metabolism in those with depression and anxiety.
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Effect of traditional Chinese medicine combined group psychotherapy on psychological distress management and gut micro-biome regulation for colorectal cancer survivors: a single-arm phase I clinical trial.
OBJECTIVE: To evaluate the efficacy and feasibility of utilizing Traditional Chinese Medicine (TCM) combined group psychotherapy intervention on psychological distress management and gut micro-biome regulation for colorectal (CRC) survivors. METHODS: A single-arm phase I clinical trial was conducted between December 2020 and December 2021 in Xiyuan Hospital and Beijing Cancer Hospital in China. Inclusion criteria included stage I-III CRC survivors after radical surgery with age between 18 and 75. The intervention was a 6-week online TCM combined group psychotherapy intervention including 90-min communication, TCM lifestyle coaching, self-acupressure guidance, and mindfulness practice led by TCM oncologist and psychiatrist each week. Outcomes were measured by Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Fear of Cancer Recurrence Inventor (FCRI), and Quality of Life Questionnaire (QLQ-C30). Fecal samples before and after intervention were collected for 16Sr RNA analysis. RESULTS: We recruited 40 CRC survivors and 38 of them finally completed all interventions with average age of 58±13 years' old. Paired t-test showed that SAS at week 2(35.4±5.8), week 4 (37.9±10.5) and week 6 (31.3±6.4) during the intervention was significantly lower than baseline (42.1±8.3, p<0.05 respectively). SDS score also declined substantially from baseline (38.8±10.7) to week 2 (28.3±8.8, p<0.001) and week 6 (25.4±7.7, p<0.001). FCRI decreased from 19.4±7.2 at baseline to 17.5±7.1 at week 4 (p=0.038) and 16.3±5.8 at week 6 (p=0.008). Although changes of QLQ-C30 were not statistically prominent, symptom burden of insomnia and fatigue significantly alleviated. The abundances of gut microbiota Intestinibacter, Terrisporobacter, Coprobacter, and Gordonibacter were all significantly elevated after intervention. CONCLUSIONS: TCM combined group psychotherapy intervention is feasible and effective to reduce CRC survivors' psychological distress and modulate certain gut bacteria which might be associated with brain-gut axis effect. It is necessary to carry out with phase II randomized controlled clinical trial.