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American Academy of Pain Medicine and Integrative Healthcare Symposium.
Featured topics: benzhydrocodone, hydrocodone, and an opioid taper program at the American Academy of Pain Medicine; and disruption of the gut microbiome by drugs plus new approaches to depression at the Integrative Healthcare Symposium.
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Impending Mental Health Issues During Coronavirus Disease 2019 - Time for Personalized Nutrition Based on the Gut Microbiota to Tide Over the Crisis?
Coronavirus disease 2019 (COVID-19) is a major pandemic facing the world today caused by SARS-CoV-2 which has implications on our mental health as well. The uncertain future, fear of job loss, lockdown and negative news all around have taken a heavy toll on the mental health of individuals from across the world. Stress and anxiety can affect the COVID-19 patients even more. Recent study suggests COVID-19 infection may lead to post-traumatic stress disorder (PTSD). Certain prebiotics and probiotics have been shown to have anxiolytic effect through gut microbiota modulation. Incidentally, preliminary report also suggests a differential microbial profile in COVID-19 patients as compared to healthy individuals. Gut microbiota's role in anxiety and depression is well studied. The importance of the "gut-brain" axis has been implicated in overall mental health. It is known that diet, environmental factors and genetics play an important role in shaping gut microbiota. Trials may be initiated to study if personalized diet and supplementation based on individual's gut microbiome profile may improve the general mental well-being of people prone to anxiety during this pandemic. Also, COVID-19 patients may be provided personalized nutritional therapy based on their gut microbiota profile to see if PTSD and anxiety symptoms can be alleviated.
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Depression-associated gut microbes, metabolites and clinical trials.
Depression is one of the most prevalent mental disorders today. Over the past decade, there has been considerable attention given to the field of gut microbiota associated with depression. A substantial body of research indicates a bidirectional communication pathway between gut microbiota and the brain. In this review, we extensively detail the correlation between gut microbiota, including Lactobacillus acidophilus and Bifidobacterium longum, and metabolites such as short-chain fatty acids (SCFAs) and 5-hydroxytryptamine (5-HT) concerning depression. Furthermore, we delve into the potential health benefits of microbiome-targeted therapies, encompassing probiotics, prebiotics, and synbiotics, in alleviating depression. Lastly, we underscore the importance of employing a constraint-based modeling framework in the era of systems medicine to contextualize metabolomic measurements and integrate multi-omics data. This approach can offer valuable insights into the complex metabolic host-microbiota interactions, enabling personalized recommendations for potential biomarkers, novel drugs, and treatments for depression.
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Combined Effects of Three High-Energy Charged Particle Beams Important for Space Flight on Brain, Behavioral and Cognitive Endpoints in B6D2F1 Female and Male Mice.
The radiation environment in deep space includes the galactic cosmic radiation with different proportions of all naturally occurring ions from protons to uranium. Most experimental animal studies for assessing the biological effects of charged particles have involved acute dose delivery for single ions and/or fractionated exposure protocols. Here, we assessed the behavioral and cognitive performance of female and male C57BL/6J × DBA2/J F1 (B6D2F1) mice 2 months following rapidly delivered, sequential irradiation with protons (1 GeV, 60%), 16O (250 MeV/n, 20%), and 28Si (263 MeV/n, 20%) at 0, 25, 50, or 200 cGy at 4-6 months of age. Cortical BDNF, CD68, and MAP-2 levels were analyzed 3 months after irradiation or sham irradiation. During the dark period, male mice irradiated with 50 cGy showed higher activity levels in the home cage than sham-irradiated mice. Mice irradiated with 50 cGy also showed increased depressive behavior in the forced swim test. When cognitive performance was assessed, sham-irradiated mice of both sexes and mice irradiated with 25 cGy showed normal responses to object recognition and novel object exploration. However, object recognition was impaired in female and male mice irradiated with 50 or 200 cGy. For cortical levels of the neurotrophic factor BDNF and the marker of microglial activation CD68, there were sex × radiation interactions. In females, but not males, there were increased CD68 levels following irradiation. In males, but not females, there were reduced BDNF levels following irradiation. A significant positive correlation between BDNF and CD68 levels was observed, suggesting a role for activated microglia in the alterations in BDNF levels. Finally, sequential beam irradiation impacted the diversity and composition of the gut microbiome. These included dose-dependent impacts and alterations to the relative abundance of several gut genera, such as Butyricicoccus and Lachnospiraceae. Thus, exposure to rapidly delivered sequential proton, 16O ion, and 28Si ion irradiation significantly affects behavioral and cognitive performance, cortical levels of CD68 and BDNF in a sex-dependent fashion, and the gut microbiome.
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Man and the Microbiome: A New Theory of Everything?
The gut microbiome is implicated in the pathophysiology of a wide range of psychological disorders. Preclinical studies have provided us with key insights into the mechanisms by which the microbiome influences bidirectional gut-brain communication. There are many signaling pathways involved, including the hypothalamic-pituitary-adrenal axis, immune modulation, tryptophan and serotonin metabolism, bile acid transformation, microbial production of neuroactive compounds, and regulation of the endocannabinoid system. The complex and widespread influence of the microbiome on many physiological and psychological processes has generated a keen interest in its therapeutic potential for depression, anxiety, autism, and other psychiatric disorders. It has been shown that the microbiome composition of people suffering with such conditions differs significantly from that of healthy controls, and although the area is in its infancy, interventional studies that alter a person's microbiome through the use of probiotics, prebiotics, or dietary change can alleviate psychopathological symptoms.
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The role of gut microbiome in the pathophysiology of PTSD, depression, and anxiety disorders.
Posttraumatic stress disorder (PTSD), depression, and anxiety disorders are prevalent and often overlapping mental health conditions with complex, multifactorial etiologies. Growing evidence implicates the gut microbiome in their pathophysiology through immune modulation, neurotransmitter regulation, and bidirectional gut-brain signaling. Findings remain fragmented and difficult to reconcile due to differences in study populations, clinical contexts, and analytic methods. This structured narrative review synthesizes current evidence on gut microbial alterations in PTSD, depression, and anxiety, while examining methodological sources of heterogeneity. We searched four databases: PubMed, Scopus, Web of Science, and PsycINFO, and identified 64 eligible studies assessing the gut microbiome composition in these disorders. Sample sizes ranged from small, exploratory cohorts (≈20 participants) to large population-based datasets (>1000 participants), with most studies conducted in China. Stool sampling and DNA extraction protocols varied widely, although 16S rRNA gene amplicon sequencing of the V3-V4 region on Illumina platforms predominated. Alpha-diversity results were inconsistent, whereas beta-diversity analyses distinguished cases from controls. Across these disorders, alterations in microbial composition was observed, including enrichment of proinflammatory and depletion of beneficial bacterial taxa. The current findings indicate that that the gut microbiome represents a promising avenue for biomarker discovery and therapeutic innovation.
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The Impact of Starvation on the Microbiome and Gut-Brain Interaction in Anorexia Nervosa.
Interactions between the gut microbiome and the brain are of increasing interest to both researchers and clinicians. Evidence is mounting on the causal role of an altered gut microbiome in inflammatory diseases such as arthritis, inflammatory bowel disease, obesity and diabetes, and psychiatric diseases like anxiety and depression. Mechanisms include altered energy harvest from food, hormonal changes, increased gut permeability, inflammation, immune response, and a direct influence on the brain and behavior. Anorexia nervosa (AN) is the third most common disease in adolescence and exacts a high burden on patients and caregivers. It often becomes chronic and has the highest mortality of all psychiatric diseases. As AN is characterized by nutritional restrictions, weight loss, and severe behavioral symptoms including weight phobia, comorbid anxiety and depression, accompanied by endocrine alterations, increased inflammation, and immune response, exploring the role of the gut microbiome is crucial. Here, we present an overview of the potential mechanisms of interaction between the gut microbiome, the host and particularly the brain in AN and summarize the initial findings of microbiome research on AN. We conclude by identifying future research directions and potential therapeutic approaches, including nutritional interventions, probiotics, prebiotics and food supplements, that could become important additions to current AN therapy.
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Intestinal microbial remodeling and metabolite regulation may be related to the improvement of social avoidance in depressed mice by Modified Xiaoyaosan.
BACKGROUND: Increased intestinal permeability is implicated in the pathogenesis of depression. Modified Xiaoyaosan (MXYS) has demonstrated antidepressant-like effects in chronic social defeat stress (CSDS) mice, particularly in improving social avoidance behavior. However, direct evidence that MXYS improves depressive behavior by regulating intestinal permeability remains lacking. METHODS: Using a CSDS-induced depression mouse model, we investigated the effects of MXYS through an integrated multi-omics approach, combining intestinal histopathology, microbiome, metabolomics, and molecular biology techniques. This strategy allowed systematic assessment of pathological changes, gut microbial composition, metabolite profiles, and protein expression. RESULTS: MXYS treatment significantly alleviated social avoidance behavior in CSDS mice. It upregulated the expression of tight junction proteins in the colon, jejunum, and hippocampus. MXYS also reduced serum permeability markers of lipopolysaccharide (LPS), D-lactate (D-Lac), and diamine oxidase (DAO), as well as concentrations of pro-inflammatory cytokines TNF-α and IL-1β in both intestinal tissues and the hippocampus. Gut microbiota analysis revealed that MXYS notably decreased the relative abundance of Desulfovibrio in the colon, which was associated with modulation of β-alanine metabolism. In the jejunum, MXYS increased the relative abundance of Clostridium sp. mbf VZ-132 and influenced glycerophospholipid metabolism. CONCLUSION: MXYS alleviates social avoidance in CSDS-induced depressed mice is associated with the restoration of intestinal barrier function via gut microbiota-mediated pathways. Specifically, it may reduces colon Desulfovibrio abundance to modulate β-alanine/aspartate metabolism and enhance claudin-1 expression, while increasing jejunal Clostridium sp. mbf VZ-132 to regulate glycerophospholipid metabolism and upregulate occludin expression. These findings suggested that MXYS may improves depression-like behavior through segment-specific microbial and metabolic modulation of intestinal permeability.
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Gut Microbiota is the Key to the Antidepressant Effect of Chaihu-Shu-Gan-San.
Accumulating evidence highlights the link between gut microbiota and depression. As an antidepressant herbal drug in clinic, Chaihu-Shu-Gan-San (CSGS) has also been used in China for the treatment of various gastrointestinal disorders. Therefore, we hypothesize that the gut microbiota might be involved in the effect of CSGS. Here, we investigated the antidepressant effects of CSGS against chronic variable stress (CVS)-induced depression rats with and without antibiotic treatment using 16S rRNA gene sequencing and ultra-performance liquid chromatography coupled with time of flight mass spectrometry (UPLC-Q-TOF/MS) based metabolome approaches. As a result, the prominent effects of CSGS against the depression-like behavioral disorder of CVS-induced rats were significantly weakened when the gut microbiota was changed after oral administration of the broad-spectrum antibiotic. The mediation of CSGS on hippocampal levels of serotonin (5-HT) and glutamic acid (Glu) was also receded with the antibiotic treatment. Further investigation on the diversity of microbiome indicated that the improvement effect of CSGS on gut microbiota dysbiosis-especially the phylum level of Firmicutes-was attenuated compared with the CSGS combined antibiotic treated one. Moreover, 3-hydroxypicolinic acid (H4) and inosine (H8) in the hippocampus were considered as important biomarkers for depression and are also associated with gut microbiota mediated CSGS efficacy. Taken together, our current study indicated that gut microbiota is a critical factor in the antidepressant effect of CSGS, and this acts in part through gut microbiota to improve depression-related biomarkers.
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Immunoprotective and neuroprotective properties of gut microbiome in psoriasis.
Psoriasis impacts nearly 100 million people globally and is associated with neuropsychiatric comorbidities such as depression and anxiety. With gut microbiome dysbiosis serving as a primary pathophysiological factor, the gut-brain-skin axis provides a crucial framework for understanding this relationship. This review evaluates the mechanisms of the gut-brain-skin axis in psoriasis pathophysiology and assesses the therapeutic potential of microbiome-based treatments, combining preclinical, clinical, and multi-omics data. Patients with psoriasis show specific gut dysbiosis patterns, including reduced microbial diversity, lower SCFA-producing bacteria (especially Faecalibacterium and Akkermansia), and increased pro-inflammatory bacteria. This microbial imbalance damages intestinal barrier integrity, triggers systemic inflammation, activates cutaneous Th17 pathways, and induces neuroinflammation through blood-brain barrier disruption. Axis communication occurs through immune-inflammatory mechanisms mediated by SCFAs and neuroendocrine pathways involving microbially-derived neurotransmitters (GABA, serotonin, dopamine). Metagenomic research indicates functional deficiencies in neurotransmitter and SCFA synthesis pathways are more significant than taxonomic alterations. Machine learning models can utilize these functional features to identify patients at risk for neuropsychiatric comorbidities and predict treatment response. Recent randomized controlled trials demonstrate that targeted interventions (probiotics, prebiotics, postbiotics, fecal microbiota transplantation) significantly improve Psoriasis Area and Severity Index scores, inflammatory markers, and microbiota composition. The evidence supports a shift toward integrated microbiome strategies, emphasizing functional approaches including mitochondrial therapies, psychobiotics, precision nutrition, and multi-omics-guided therapies.