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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.
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Gut-brain axis in post-traumatic stress disorder: microbial - mediated mechanisms and new therapeutic approaches - A narrative review.
Post-traumatic stress disorder (PTSD) is a severe mental disorder that occurs after experiencing or witnessing a traumatic event. Not only does this disorder severely impair the quality of life and emotional wellbeing of patients, but in recent years the global rate of PTSD diagnoses has increased to 1.5-2 times, and the prevalence of PTSD associated with COVID-19 events in particular has surged to 10%-25%, underscoring the urgency of developing effective treatments. The lifetime prevalence of PTSD in the general population is estimated to be approximately 3.9%, while in high-risk populations, such as war veterans, it can be as high as 30%. As a key pathway connecting the central nervous system to peripheral organs, the gut-brain axis has received increasing attention for its role in PTSD. Although the gut-brain axis has been shown to be associated with several psychiatric disorders, especially depression, its specific role in PTSD remains undercharacterized. Existing studies suggest that specific strains of Lactobacillus (e.g., Lactobacillus reuteri) may alleviate inflammatory responses and improve PTSD-like behaviors by down-regulating the expression of pro-inflammatory factors (IL-6 and TNF-α). In this study, we used a narrative review approach to sort out the research progress of gut microbiota alteration in PTSD, and compared the characteristics of changes in specific microbial taxa (e.g., Bacteroides, Lactobacillus, etc.), the index of microbiota diversity (α/β diversity), and the levels of inflammatory markers (e.g., IL-6, TNF-α) between the animal model and the human patients, respectively, in order to We further explored the potential pathogenic mechanisms mediated by microorganisms, such as influencing the vagal pathway, hypothalamic-pituitary-adrenal (HPA) axis function, immune system and other processes involved in the pathology of PTSD, and summarized the intervention strategies targeting gut microecology, such as probiotic supplementation, dietary interventions and fecal bacteria transplantation.
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Neurological and Psychiatric Adverse Effects of Antimicrobials.
Antimicrobials are a widely used class of medications, but several of them are associated with neurological and psychiatric side effects. The exact incidence of neurotoxicity with anti-infectives is unknown, although it is estimated to be < 1%. Neurotoxicity occurs with all classes of antimicrobials, such as antibiotics, antimycobacterials, antivirals, antifungals and antiretrovirals, with side effects ranging from headaches, anxiety and depression to confusion, delirium, psychosis, mania and seizures, among others. It is important to consider these possible side effects to prevent misdiagnosis or delayed treatment as drug withdrawal can be associated with reversibility in most cases. This article highlights the different neurotoxic effects of a range of antimicrobials, discusses proposed mechanisms of onset and offers general management recommendations. The effects of antibiotics on the gut microbiome and how they may ultimately affect cognition is also briefly examined.
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Research Progress on the Pathogenesis of Post-Stroke Depression.
Poststroke depression (PSD) is a common neuropsychiatric complication following stroke. Clinically, it is characterized by persistent low mood, cognitive dysfunction, and somatic symptoms, which severely impact the recovery and quality of life of stroke patients, making it an urgent issue in clinical practice. Currently, the pathogenesis of PSD remains incompletely understood. This study presents a narrative review of the literature from PubMed, Web of Science, and CNKI, with a particular focus on research conducted between 2021 and 2025. The findings reveal that advancements in neuroscience, immunology, and gut microbiome studies have contributed to important breakthroughs in understanding the mechanisms underlying PSD, such as the interaction between the hypothalamic-pituitary-adrenal (HPA) axis and neuroinflammation. In terms of treatment, several novel approaches have emerged. Traditional Chinese medicine (TCM) has attracted increasing attention due to its low cost, high safety, and minimal side effects. Herbal formulas have shown promising therapeutic effects for PSD. Moreover, combination therapies, such as acupuncture combined with repetitive transcranial magnetic stimulation (rTMS), have been demonstrated to be more effective than monotherapies. This review summarizes the multidimensional pathophysiology of PSD, including neurotransmitter imbalance, neuroinflammation, impaired neuroplasticity, structural brain damage, HPA axis dysregulation, gut-brain axis imbalance, and psychosocial factors. Additionally, current clinical treatment strategies for PSD are reviewed, with the aim of providing a theoretical foundation for early diagnosis, timely intervention, the development of novel anti-PSD therapies, and the establishment of more comprehensive treatment strategies for PSD.
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Microbial glutamate metabolism predicts intravenous cocaine self-administration in diversity outbred mice.
The gut microbiome is thought to play a critical role in the onset and development of psychiatric disorders, including depression and substance use disorder (SUD). To test the hypothesis that the microbiome affects addiction predisposing behaviors and cocaine intravenous self-administration (IVSA) and to identify specific microbes involved in the relationship, we performed 16S rRNA gene sequencing on feces from 228 diversity outbred mice. Twelve open field measures, two light-dark assay measures, one hole board and novelty place preference measure significantly differed between mice that acquired cocaine IVSA (ACQ) and those that failed to acquire IVSA (FACQ). We found that ACQ mice are more active and exploratory and display decreased fear than FACQ mice. The microbial abundances that differentiated ACQ from FACQ mice were an increased abundance of Barnesiella, Ruminococcus, and Robinsoniella and decreased Clostridium IV in ACQ mice. There was a sex-specific correlation between ACQ and microbial abundance, a reduced Lactobacillus abundance in ACQ male mice, and a decreased Blautia abundance in female ACQ mice. The abundance of Robinsoniella was correlated, and Clostridium IV inversely correlated with the number of doses of cocaine self-administered during acquisition. Functional analysis of the microbiome composition of a subset of mice suggested that gut-brain modules encoding glutamate metabolism genes are associated with the propensity to self-administer cocaine. These findings establish associations between the microbiome composition and glutamate metabolic potential and the ability to acquire cocaine IVSA thus indicating the potential translational impact of targeting the gut microbiome or microbial metabolites for treatment of SUD. This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies".
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Gut Biome and Mental Health: Do Probiotics Work?
Mental health conditions have been linked closely to an imbalance of microbiota in the gut, leading to disruption of the microbiome (dysbiosis). Several neurotransmitters, such as GABA (gamma-aminobutyric acid), serotonin, and glutamate, are produced in the gut, which are associated with anxiety and depressive symptoms. Mental health and the gut have been linked closely, and many mental illnesses have been associated with gut dysbiosis. Probiotics are marketed to improve gut health, act as mood enhancers, and be effective in reducing stress as unregulated over-the-counter supplements. Given healthcare disparities and patient-doctor gaps across the globe, this review aims to appraise the literature on probiotics for the prevention and treatment of mental disorders. PubMed and Google Scholar databases were searched till March 2023 using the MeSH words "prebiotics," "probiotics," "synbiotics," and "psychobiotics." Out of 207 studies, 26 studies met the inclusion criteria and were included in the review. Studies suggest probiotics could be an effective and economical adjunct therapy; however, due to weak study design and low power, the results are inconclusive. Their use is not without risks, and healthcare providers need close supervision until more robust longitudinal studies are conducted to appraise their efficacy and safety profiles.