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Gut Microbiome dysbiosis and immune activation correlate with somatic and neuropsychiatric symptoms in COVID-19 patients.
BACKGROUND: Infection with SARS-CoV-2, the virus responsible for COVID-19, can lead to a range of physical symptoms and mental health challenges, including stress, anxiety, and depression. These effects are particularly pronounced in hospitalized patients, likely due to the virus's direct and indirect impact on the nervous system. Gut dysbiosis, an imbalance in the gut microbiome, has been implicated in immune dysfunction and chronic inflammation in COVID-19 patients. However, the interactions between gut microbiome composition and the physical and mental symptoms of COVID-19 remain incompletely understood. METHODS: We investigated the association between physical and mental symptoms, cytokine profiles, and gut microbiota composition in 124 hospitalized COVID-19 patients. We collected data on demographics, COVID-19 severity, and mental health indicators (stress, anxiety, and depression). Gut microbiome profiling was performed using full-length 16 S rRNA gene sequencing to evaluate microbial diversity and composition. RESULTS: COVID-19 severity was categorized as low (27.4%), moderate (29.8%), or critical (42.8%). Common symptoms included fever (66.1%) and cough (55.6%), while somatic symptoms (27.3%), anxiety (27.3%), depressive symptoms (39%), and stress (80.5%) were frequently self-reported. Elevated interleukin-6 levels in severe cases highlighted systemic inflammation, reduced gut bacterial diversity, particularly among women and obese patients, correlated with higher disease severity. Notably, the genus Mitsuokella was associated with increased physical symptoms and mental distress, while Granulicatella was linked to critical illness. CONCLUSIONS: Our findings reveal significant associations between mental health status, systemic inflammation, and gut dysbiosis in hospitalized COVID-19 patients. These results indicate the potential for microbiome-targeted therapies to mitigate psychological and physical complications and improve recovery outcomes in this population.
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Role of the gut microbiome in psychological symptoms associated with inflammatory bowel diseases.
The brain-gut axis constitutes the basis for the bidirectional communication between the central nervous system and the gastrointestinal tract driven by neural, hormonal, metabolic, immunological, and microbial signals. Alterations in the gut microbiome composition as observed in inflammatory bowel diseases can modulate brain function and emerging empirical evidence has indicated that interactions among the brain-gut microbiome-axis seem to play a significant role in the pathogenesis of both inflammatory bowel diseases and psychiatric disorders and their comorbidity. Yet, the immunological and molecular mechanisms underlying the co-occurrence of inflammatory bowel diseases and psychological symptoms are still poorly understood. The aim of this narrative review is to highlight contemporary empirical findings supporting a pivotal role of the gut microbiome in the pathophysiology of highly prevalent neuropsychiatric symptoms in inflammatory bowel diseases such as fatigue, depression, and anxiety. Finally, we focus on microbiome modulation as potential treatment option for comorbid neuropsychiatric symptoms in immune-mediated diseases and especially in inflammatory bowel diseases. High-quality clinical trials are required to clarify how microbiome modulation through dietary interventions or probiotic, prebiotic or synbiotic treatment can be used clinically to improve mental health and thus quality of life of patients with inflammatory bowel diseases.
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Lactobacillus rhamnosus: An emerging probiotic with therapeutic potential for depression.
Depression, a complex psychological disorder, involves multiple biological pathways in its pathogenesis. In recent years, the gut-brain axis theory has provided novel insights into the pathogenesis of depression, particularly the crucial role of the gut microbiota in mood regulation. While there remains no universal consensus on the most efficacious strains for depression treatment, Lactobacillus rhamnosus has risen to prominence within the realm of probiotics for its potential to positively modulate depressive symptoms. This review preliminarily explores the clinical significance of Lactobacillus rhamnosus in the treatment of depression and summarizes the potential mechanisms by which Lactobacillus rhamnosus treats depression, including its regulation of gut microbiota, alterations in gene expression, improvement of intestinal barrier function, maintenance of neurotransmitter balance, suppression of inflammatory responses, modulation of the immune system, coping with oxidative stress, and optimization of metabolic processes. Future research needs to further explore these mechanisms and combine them with clinical research results to optimize treatment plans and provide more effective treatment options for patients with depression.
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The saNeuroGut Initiative: Investigating the Gut Microbiome and Symptoms of Anxiety, Depression, and Posttraumatic Stress.
INTRODUCTION: Common mental disorders, such as anxiety disorders, depression, and posttraumatic stress disorder (PTSD), present a substantial health and economic burden. The gut microbiome has been associated with these psychiatric disorders via the microbiome-gut-brain axis. However, previous studies have focused on the associations between the gut microbiome and common mental disorders in European, North American, and Asian populations. As part of the saNeuroGut Initiative, we assessed associations between gut microbial composition and self-reported symptoms of anxiety, depression, and posttraumatic stress (PTS) among South African adults. METHODS: Participants completed validated, online self-report questionnaires to evaluate symptoms of state anxiety, trait anxiety, depression, and PTSD. Eighty-six stool-derived microbial DNA samples underwent sequencing of the V4 region of the 16S rRNA gene to characterise gut bacterial taxa in the sample. RESULTS: No significant associations were observed between symptom severity scores and alpha (Shannon and Simpson indices) and beta (Aitchison distances) diversity metrics. Linear regression models revealed that the abundances of Catenibacterium, Collinsella, and Holdemanella were significantly positively associated with the severity of PTS symptoms. CONCLUSION: Catenibacterium, Collinsella, and Holdemanella have each previously been associated with various psychiatric disorders, with Catenibacterium having been positively associated with symptoms of PTSD in another South African cohort. This study sheds light on the relationship between the human gut microbiome and symptoms of anxiety, depression, and PTS in a South African adult sample.
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rTMS ameliorates depressive-like behaviors and regulates the gut microbiome and medium- and long-chain fatty acids in mice exposed to chronic unpredictable mild stress.
INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is a clinically useful therapy for depression. However, the effects of rTMS on the metabolism of fatty acids (FAs) and the composition of gut microbiota in depression are not well established. METHODS: Mice received rTMS (15 Hz, 1.26 T) for seven consecutive days after exposure to chronic unpredictable mild stress (CUMS). The subsequent depressive-like behaviors, the composition of gut microbiota of stool samples, as well as medium- and long-chain fatty acids (MLCFAs) in the plasma, prefrontal cortex (PFC), and hippocampus (HPC) were evaluated. RESULTS: CUMS induced remarkable changes in gut microbiotas and fatty acids, specifically in community diversity of gut microbiotas and PUFAs in the brain. 15 Hz rTMS treatment alleviates depressive-like behaviors and partially normalized CUMS induced alterations of microbiotas and MLCFAs, especially the abundance of Cyanobacteria, Actinobacteriota, and levels of polyunsaturated fatty acids (PUFAs) in the hippocampus and PFC. CONCLUSION: These findings revealed that the modulation of gut microbiotas and PUFAs metabolism might partly contribute to the antidepressant effect of rTMS.
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Gut microbiome predicts cognitive function and depressive symptoms in late life.
Depression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states.
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A Pilot Interaction Analysis of Gut Microbiota and Peripheral Markers of Aging in Severe Psychiatric Disorders: A Role for Lachnoclostridium?
Excessive predominance of pathological species in the gut microbiota could increase the production of inflammatory mediators at the gut level and, via modification of the gut-blood barrier, at the systemic level. This pro-inflammatory state could, in turn, increase biological aging that is generally proxied by telomere shortening. In this study, we present findings from a secondary interaction analysis of gut microbiota, aging, and inflammatory marker data from a cohort of patients with different diagnoses of severe mental disorders. We analyzed 15 controls, 35 patients with schizophrenia (SCZ), and 31 patients with major depressive disorder (MDD) recruited among those attending a community mental health center (50 males and 31 females, mean and median age 46.8 and 46.3 years, respectively). We performed 16S rRNA sequencing as well as measurement of telomere length via quantitative fluorescence in situ hybridization and high-sensitivity C-reactive protein. We applied statistical modeling with logistic regression to test for interaction between gut microbiota and these markers. Our results showed statistically significant interactions between telomere length and gut microbiota pointing to the genus Lachnostridium, which remained significantly associated with a reduced likelihood of MDD even after adjustment for a series of covariates. Although exploratory, these findings show that specific gut microbiota signatures overexpressing Lachnoclostridium and interacting with biological aging could modulate the liability for MDD.
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An updated systematic review and appraisal of the pathophysiologic mechanisms of probiotics in alleviating depression.
Gut-brain axis has emerged as a promising strategy for managing depression. Probiotic supplements, which modulate the gut microbiome, are suggested to enhance gut-brain communication and improve depressive symptoms and cognitive function. However, the acceptance of probiotics in managing depression remains contentious. This study aimed to evaluate the effects of probiotics on depression through meta-analysis and to assess their mechanisms of action, focusing on changes in gut microbial composition and neural mechanisms. A total of 12 randomized controlled trials from PubMed, Web of Science, and Scopus, up to January 1, 2024, were included. Nine studies consistently demonstrated improvements in depressive symptoms, gut microbiota, inflammatory markers, cognitive function, and mood regulation. The meta-analysis indicated a significant reduction in depressive symptoms with probiotics compared to placebo, with a mean difference of - 1.94 (95% CI = -3.56 to - 0.32, p = 0.02, I2 = 69%). The Hamilton Depression Rating Scale (HAM-D), which showed substantial improvement, with a mean difference of - 3.27 (95% CI = -6.42 to - 0.12, p = 0.04, I2 = 82%), is a preferred tool for further studies due to its comprehensive symptom coverage and strong psychometric properties. Probiotic strains such as Lactobacillus plantarum subspecies JYLP-326 and Bifidobacterium breve CCFM1025 were particularly effective, while multi-strain probiotics generally showed more consistent effects than single-strain interventions. Probiotics show promising potential in alleviating depression through their anti-inflammatory effects, gut microbiota modulation, cognitive function enhancement, and possible influence on brain structure and neurotransmitter systems. Despite some variability in trial results, this review provides updated insights for medical practitioners, highlighting probiotics as a viable treatment option for depression.
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Alteration of behavior and monoamine levels attributable to Lactobacillus plantarum PS128 in germ-free mice.
Probiotics, defined as live bacteria or bacterial products, confer a significant health benefit to the host, including amelioration of anxiety-like behavior and psychiatric illnesses. Here we administered Lactobacillus plantarum PS128 (PS128) to a germ-free (GF) mouse model to investigate the impact of the gut-brain axis on emotional behaviors. First, we demonstrated that chronic administration of live PS128 showed no adverse effects on physical health. Then, we found that administration of live PS128 significantly increased the total distance traveled in the open field test and decreased the time spent in the closed arm in the elevated plus maze test, whereas the administration of PS128 had no significant effects in the depression-like behaviors of GF mice. Also, chronic live PS128 ingestion significantly increased the levels of both serotonin and dopamine in the striatum, but not in the prefrontal cortex or hippocampus. These results suggest that the chronic administration of PS128 is safe and could induce changes in emotional behaviors. The behavioral changes are correlated with the increase in the monoamine neurotransmitters in the striatum. These findings suggest that daily intake of the L. plantarum strain PS128 could improve anxiety-like behaviors and may be helpful in ameliorating neuropsychiatric disorders.
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A human-derived Bacteroides strain attenuates depressive-like behavior in a rat model of social defeat-induced stress.
BACKGROUND: The gut microbiome has been linked to mood disorders via communication along the gut-brain axis. We previously found levels of fecal Bacteroides were inversely associated with brain signatures of depression in the prefrontal cortex of human subjects. Bacteroides are important human commensals, playing a keystone role in regulating the immune system and producing bioactive metabolites, like the neurotransmitter gamma-aminobutyric acid and B vitamins. METHODS: To better understand the link between Bacteroides and depression - and test a candidate novel next-generation probiotic - we administered a human-derived Bacteroides salyersiae strain, HB32, orally in rats that were subjected to the repeated social defeat model of stress-induced depression. The fecal microbiome and the prefrontal cortex transcriptome were then profiled for intervention-induced alterations. RESULTS: Orally delivered B. salyersiae HB32 reduced depressive-like behavior in male rats comparable to the drug ketamine, independently of the strain being administered in its viable or inactivated (iHB32) form. Mechanistically, we observed that stress-induced anhedonia required the vagus nerve for its phenotype to develop, suggesting crosstalk between the gut and the brain. In support of this, we found HB32 and iHB32, but not ketamine, rescued stress-induced differential expression patterns in the prefrontal cortex, including those related to serotonin signaling and oxidative stress. In the gut, prolonged exposure to social defeat led to broad shifts in the composition of the gut microbiome, with a predominant reduction of the endogenous Bacteroides. Administration of HB32, iHB32, and ketamine attenuated the impact of stress on the microbiome, and intake of live HB32 resulted in a significant increase of the B. salyersiae species in the fecal microbiome. CONCLUSIONS: Depressive-like behavior in male rats induced by repeated social defeat requires vagal signaling, suggesting gut-brain-axis crosstalk. In animals with an intact vagus nerve, oral administration of viable or inactivated B. salyersiae HB32 reversed behavioral changes induced by chronic stress at levels comparable to ketamine. Additionally, supplementation of HB32 and iHB32 was associated with attenuation of stress-related microbiome and prefrontal cortex transcriptional changes.