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Inflammatory Stress Effects on Health and Function After Spinal Cord Injury.
Background: Injury to the spinal cord produces immediate, adaptive inflammatory responses that can exacerbate the initial injury and lead to secondary damage. Thus far, researchers and clinicians have focused on modulating acute inflammation to preserve sensorimotor function. However, this singular approach risks overlooking how chronic inflammation negatively impacts the broader health of persons with a spinal cord injury (SCI). Objective: The aim of this monograph was to discuss interrelated processes causing persistent inflammatory stress after SCI, along with associated health risks. We review archetypal factors that contribute to a chronic inflammatory state, including response to injury, acute infection, and autonomic dysreflexia. Secondary complications producing and exacerbating inflammation are also discussed, including pain, depression, obesity, and injury to the integumentary and skeletal systems. Finally, we discuss the role of bacteria and the gut microbiome in this process and then conclude with a discussion on how a pro-inflammatory phenotype promotes an elevated risk for cardiovascular disease after injury. Conclusions: Effectively managing chronic inflammation should be a high priority for clinicians and researchers who seek to improve the health and life quality of persons with SCI. Chronic inflammation worsens secondary medical complications and amplifies the risk for cardiometabolic disorders after injury, directly impacting both the quality of life and mortality risk after SCI. Inflammation can worsen pain and depression and even hinder neurological recovery. It is, therefore, imperative that countermeasures to chronic inflammation are routinely considered from the point of initial injury and proceeding throughout the lifespan of the individual with SCI.
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Alteration of faecal microbiota balance related to long-term deep meditation.
BACKGROUND: Advancements in research have confirmed that gut microbiota can influence health through the microbiota-gut-brain axis. Meditation, as an inner mental exercise, can positively impact the regulation of an individual's physical and mental health. However, few studies have comprehensively investigated faecal microbiota following long-term (several years) deep meditation. Therefore, we propose that long-term meditation may regulate gut microbiota homeostasis and, in turn, affect physical and mental health. AIMS: To investigate the effects of long-term deep meditation on the gut microbiome structure. METHODS: To examine the intestinal flora, 16S rRNA gene sequencing was performed on faecal samples of 56 Tibetan Buddhist monks and neighbouring residents. Based on the sequencing data, linear discriminant analysis effect size (LEfSe) was employed to identify differential intestinal microbial communities between the two groups. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis was used to predict the function of faecal microbiota. In addition, we evaluated biochemical indices in the plasma. RESULTS: The α-diversity indices of the meditation and control groups differed significantly. At the genus level, Prevotella and Bacteroides were significantly enriched in the meditation group. According to the LEfSe analysis, two beneficial bacterial genera (Megamonas and Faecalibacterium) were significantly enriched in the meditation group. Functional predictive analysis further showed that several pathways-including glycan biosynthesis, metabolism and lipopolysaccharide biosynthesis-were significantly enriched in the meditation group. Moreover, plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. CONCLUSIONS: Long-term traditional Tibetan Buddhist meditation may positively impact physical and mental health. We confirmed that the gut microbiota composition differed between the monks and control subjects. The microbiota enriched in monks was associated with a reduced risk of anxiety, depression and cardiovascular disease and could enhance immune function. Overall, these results suggest that meditation plays a positive role in psychosomatic conditions and well-being.
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Epigenetic Alterations of Brain Non-Neuronal Cells in Major Mental Diseases.
The tissue-specific expression and epigenetic dysregulation of many genes in cells derived from the postmortem brains of patients have been reported to provide a fundamental biological framework for major mental diseases such as autism, schizophrenia, bipolar disorder, and major depression. However, until recently, the impact of non-neuronal brain cells, which arises due to cell-type-specific alterations, has not been adequately scrutinized; this is because of the absence of techniques that directly evaluate their functionality. With the emergence of single-cell technologies, such as RNA sequencing (RNA-seq) and other novel techniques, various studies have now started to uncover the cell-type-specific expression and DNA methylation regulation of many genes (e.g., TREM2, MECP2, SLC1A2, TGFB2, NTRK2, S100B, KCNJ10, and HMGB1, and several complement genes such as C1q, C3, C3R, and C4) in the non-neuronal brain cells involved in the pathogenesis of mental diseases. Additionally, several lines of experimental evidence indicate that inflammation and inflammation-induced oxidative stress, as well as many insidious/latent infectious elements including the gut microbiome, alter the expression status and the epigenetic landscapes of brain non-neuronal cells. Here, we present supporting evidence highlighting the importance of the contribution of the brain's non-neuronal cells (in particular, microglia and different types of astrocytes) in the pathogenesis of mental diseases. Furthermore, we also address the potential impacts of the gut microbiome in the dysfunction of enteric and brain glia, as well as astrocytes, which, in turn, may affect neuronal functions in mental disorders. Finally, we present evidence that supports that microbiota transplantations from the affected individuals or mice provoke the corresponding disease-like behavior in the recipient mice, while specific bacterial species may have beneficial effects.
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Safety and Efficacy of Ketogenic Diet in the Management of Multiple Sclerosis: A Systematic Review.
This systematic review examines the safety and efficacy of ketogenic diets (KD) in multiple sclerosis (MS) management. Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched five major databases through April 2025, identifying six relevant studies published between 2017 and 2024. These studies, predominantly focusing on relapsing-remitting MS, demonstrate consistent benefits of ketogenic interventions across multiple domains. Findings suggest KD normalizes gut microbiome composition, reduces pro-inflammatory markers (ALOX5, COX1, COX2), improves body composition with favorable changes in adipokines (decreased leptin, increased adiponectin), and enhances clinical outcomes, including fatigue, depression, sleep quality, and quality of life measures. Objective neurological improvements were observed in Expanded Disability Status Scale (EDSS) scores, walking ability, and manual dexterity. Adherence rates were notably high, with benefits partially persisting after intervention completion. The metabolic shift induced by ketosis may provide alternative neuronal energy substrates, reduce oxidative stress, and attenuate neuroinflammation. Despite limitations including small sample sizes and study heterogeneity, these preliminary findings suggest KDs represent a promising adjunctive approach in MS management, addressing both inflammatory and neurodegenerative components of the disease. Larger, controlled trials with longer follow-up periods are warranted to establish long-term safety and efficacy profiles.
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Efficacy of prebiotics, probiotics, and postbiotics on depression: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND: Depression is a global health issue linked to gut-microbiota-dysbiosis, which influences brain function through the gut-brain axis. Dietary biotics offer a promising therapeutic avenue. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the efficacy of biotic interventions in managing depression. METHODOLOGY: Five databases were searched for randomized controlled trials (RCTs) from 2016 to 2024. 27 RCTs with a control group and standard depression rating scales were included. Data extraction and risk-of-bias assessment were conducted independently by two reviewers, with certainty-of-evidence appraised using GRADE. Meta-analyses employed standardized mean differences, with subgroup analyses by intervention duration (short: <6 weeks, medium: 6-12 weeks, and long: >12 weeks), respectively. RESULTS: Probiotic interventions showed no significant effects in short and medium-duration subgroups (6 and 12 studies, respectively), both of which demonstrated substantial heterogeneity. A significant effect was observed in the long-duration subgroup (2 studies) with no observed heterogeneity, although based on limited evidence. Prebiotic interventions showed no significant effects, while postbiotic interventions demonstrated no clear effects across durations, with variable heterogeneity. Sensitivity analyses were generally consistent with the main findings. Overall certainty of evidence was rated as moderate due to inconsistency across studies. CONCLUSION: Probiotics administered over longer durations may be associated with improvements in depressive symptoms, although this finding is based on limited evidence. Evidence for prebiotic and postbiotic interventions remains inconclusive. Overall, substantial heterogeneity was observed across studies, and findings should be interpreted cautiously. Further well-designed randomized controlled trials are needed to clarify the effects of microbiome-targeted interventions in depression.
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Effect of moderate aerobic exercises on symptoms of functional dyspepsia.
BACKGROUND: Functional dyspepsia (FD) is a commonly encountered entity worldwide and is difficult to treat. Most of the treatment modalities have low-quality evidence for use, except for proton pump inhibitors. Aerobic exercise has been shown to improve the symptoms, but its direct effect on symptoms has never been studied. The objective was to study the effects of moderate aerobic exercise on symptoms of FD and to compare the effect of conventional treatment alone vs. exercise plus conventional treatment. METHODS: Out of 112 patients, 72 were randomly divided into controls (conventional treatment; n=36) and experimental (aerobic exercise for 30 min per session, 5 times a week for 6 weeks with conventional treatment; n=36) groups. Both the groups were assessed on day 1 and at the end of 6 weeks, using Glasgow Dyspepsia Severity Score (GDSS), Depression Anxiety Stress Scales-42 (DASS-42), and visual analogue scale (VAS). RESULTS: Pre-treatment GDSS, DASS-42, and VAS in the experimental group were significantly different as compared to the post-treatment scores (p=0.00019, p=0.0002, p=0.00019, respectively). Even in the control group, pre- and post-treatment GDSS, DASS-42, and VAS scores were significantly different (p=0.00019, p=0.0002, p=0.00019, respectively). However, on the head-to-head comparison of the 2 groups, scores at the end of 6 weeks were significantly different (p< 0.05), in favor of the experimental group. CONCLUSION: Aerobic exercise as an auxiliary therapy to conventional treatment has better outcomes in the functional well-being of dyspepsia.
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[Physical activity - the Holy Grail of modern medicine?].
Movement is the basic attribute of life. It is not surprising that the return to regular physical activity is a very effective and cheap means of preventing and treating most non-cummunicable diseases. Therefore, every physician should be able to prescribe a suitable physical activity. The minimum amount of physical activity with proven effects in primary prevention of chronic diseases is relatively low: 150 minutes of moderate physical activity or 75 minutes of high intensity exercise per week or a combination of the two. The simplest and safe way of physical activity is walking (at least 10 000 steps/day or 6 000 steps/day on top of daily activities). The FITT model is a more sophisticated way of prescribing physical activity that already requires a stress test. Patients at risk of atherosclerosis or with any manifestation of atherosclerosis (patients with coronary artery disease, post-stroke, peripheral artery disease) benefit from exercise as well as patients with chronic heart failure. Physical activity also helps patients with lung disease (COPD, asthma), metabolic diseases (diabetes mellitus, obesity, osteoporosis) and also rheumatologic diseases. Regular exercise improves cognitive function, reduces depression and anxiety, and helps addicted people. Recently, it has been shown that exercise also changes the gut microbiome. One of the mechanisms that contribute to the beneficial effect of exercise is so-called "exercise factors" - myokines. Physical activity, when properly prescribed, is an inexpensive and universal medication with minimal side effects. It is our "home pharmacy" we always have with us.Key words: cancer - cardiovascular diseases - neuropsychiatric diseases - physical activity - type 2 diabetes.
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Adolescent use of potential novel probiotic Rouxiella badensis subsp. acadiensis (Canan SV-53) mitigates pubertal LPS-Induced behavioral changes in adulthood in a sex-specific manner by modulating 5HT1A receptors expression in specific brain areas.
Adolescence is a critical period of development during which the brain undergoes significant remodeling that impacts behavior later in life. Exposure to stress, and especially immune challenge, during this period triggers changes in brain function resulting in the development of mental disorders in adulthood, such as depression and anxiety. Previous studies from our laboratory have shown that a single exposure to LPS (lipopolysaccharide) during puberty causes enduring depression-like behaviour in females and anxiety-like behaviours in males. However, administration of probiotics during puberty blocked the enduring effects of LPS on depression-like and anxiety-like behaviors in female and male mice, respectively. These results suggest that the gut microbiome is a mediator of the effects of stress on mental health. The objective of the current study is to examine the effectiveness of a novel probiotic Rouxiella badensis subsp. acadiensis (Canan SV-53) in blocking LPS-induced anxiety-like and depression-like behaviors in adult male and female mice. Our results showed that Rouxiella badensis subsp. acadiensis (Canan SV-53) blocked LPS-induced depression-like behavior in female mice. We also found that pubertal treatment with Rouxiella badensis subsp. acadiensis (Canan SV-53) mitigated the LPS-induced decrease in 5HT1A expression in CA1 as well as the LPS-induced increase in 5HT1A expression in the raphe-nuclei in female mice. Contrary to our predictions, pubertal LPS treatment at 6 weeks of age did not induce enduring anxiety-like behavior in males. There was also no difference in anxiety-like behavior between the LPS-sucrose and LPS-probiotic male groups. However, pubertal LPS treatment increased the expression of 5HT1A receptors in the DRN in males, while probiotic exposure mitigated this increase. Our study highlights the consequences of stress exposure (immune challenge) on mental health in adulthood taking into consideration 5HT1A receptors expression at different regions of the brain. It also emphasizes on the importance of considering adolescence as window of opportunities during which probiotic use can alleviate the long-term neural and behavioral alterations induced by stress.
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Role of the gut-brain axis via the subdiaphragmatic vagus nerve in stress resilience of 3,4-methylenedioxymethamphetamine in mice exposed to chronic restrain stress.
3,4-Methylenedioxymethamphetamine (MDMA) is the most widely used illicit substance worldwide. Nevertheless, recent observational studies demonstrated that lifetime MDMA use among U.S. adults was associated with a lower risk of depression and suicide thoughts. We recently reported that the gut-brain axis may contribute to MDMA-induced stress resilience in mice. To further explore this, we investigated the effects of subdiaphragmatic vagotomy (SDV) in modulating the stress resilience effects of MDMA in mice subjected to chronic restrain stress (CRS). Pretreatment with MDMA (10 mg/kg/day for 14 days) blocked anhedonia-like behavior and reduced expression of synaptic proteins and brain-derived neurotrophic factor in the prefrontal cortex (PFC) of CRS-exposed mice. Interestingly, SDV blocked the beneficial effects of MDMA on these alterations in CRS-exposed mice. Analysis of gut microbiome revealed alterations in four measures of α-diversity between the sham + MDMA + CRS group and the SDV + MDMA + CRS group. Moreover, specific microbes differed between the vehicle + CRS group and the MDMA + CRS group, and further differences in microbial composition were observed among all four groups. Untargeted metabolomics analysis showed that SDV prevented the increase in plasma levels of three compounds [lactic acid, 1-(2-hydroxyethyl)-2,2,6-tetramethyl-4-piperidinol, 8-acetyl-7-hydroxyvumaline] observed in the sham + MDMA + CRS group. Interestingly, positive correlations were found between the plasma levels of two of these compounds and the abundance of several microbes across all groups. In conclusion, our data suggest that the gut-brain axis via the subdiaphragmatic vagus nerve might contribute to the stress resilience of MDMA.
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Effect of very low-protein diets supplemented with branched-chain amino acids on energy balance, plasma metabolomics and fecal microbiome of pigs.
Feeding pigs with very-low protein (VLP) diets while supplemented with limiting amino acids (AA) results in decreased growth. The objective of this study was to determine if supplementing VLP diets with branched-chain AA (BCAA) would reverse the negative effects of these diets on growth and whether this is associated with alterations in energy balance, blood metabolomics and fecal microbiota composition. Twenty-four nursery pigs were weight-matched, individually housed and allotted into following treatments (n = 8/group): control (CON), low protein (LP) and LP supplemented with BCAA (LP + BCAA) for 4 weeks. Relative to CON, pigs fed with LP had lower feed intake (FI) and body weight (BW) throughout the study, but those fed with LP + BCAA improved overall FI computed for 4 weeks, tended to increase the overall average daily gain, delayed the FI and BW depression for ~ 2 weeks and had transiently higher energy expenditure. Feeding pigs with LP + BCAA impacted the phenylalanine and protein metabolism and fatty acids synthesis pathways. Compared to CON, the LP + BCAA group had higher abundance of Paludibacteraceae and Synergistaceae and reduced populations of Streptococcaceae, Oxyphotobacteria_unclassified, Pseudomonadaceae and Shewanellaceae in their feces. Thus, supplementing VLP diets with BCAA temporarily annuls the adverse effects of these diets on growth, which is linked with alterations in energy balance and metabolic and gut microbiome profile.