Emerging evidence highlights the role of gut microbiome in mental health disorders, including depression, raising the question whether the action of antidepressants could be mediated, at least in part, via the microbiome-gut-brain axis. To explore this, we subjected a St. John's wort extract (STW 3-VI), clinically proven to be effective in mild to moderate depression, to a model of the upper and lower intestinal tract, including static in vitro predigestion followed by ex vivo incubation with human microbiota samples. To cover the interindividual diversity of gut microbiome composition, fecal samples from ten healthy volunteers were used. Although unchanged levels of most annotated compounds were observed during simulated upper intestinal tract digestion, incubation with fecal microbiota led to a significant change of the chemical profile of the extract. While hyperforins remained stable, flavonoids and hypericins were rapidly biotransformed, suggesting that they may act as prodrugs. Several metabolites were formed, many of which are known to be involved in gut-brain communication. Differential abundance analysis revealed significant changes in microbiome composition, particularly for taxa known to be potentially associated with depression. Among others, the Firmicutes/Bacteroidetes ratio, known to be lowered in depressive patients, was increased. Functional profiling revealed modulation of pathways involved in gut-brain communication, such as tyrosine and tryptophan metabolism. These bidirectional interactions suggest for the first time the gut microbiome as a potential mediator of the pharmacological effects of St. John's wort extracts via the microbiome-gut-brain axis.

Major depressive disorder is a prevalent mental illness, with SNRIs constituting a mainstay of the psychopharmacological approach to its clinical management. Despite their impact on adherence, efficacy, and relapse risk, gastrointestinal adverse events (AEs) linked to SNRIs remain under-explored. This study systematically evaluated gastrointestinal adverse events associated with SNRIs by leveraging the FDA Adverse Event Reporting System (FAERS) database. A retrospective analysis of FAERS data from 2004 to 2024 identified 114,148 reports involving five SNRI drugs (venlafaxine, desvenlafaxine, milnacipran, levomilnacipran, and duloxetine). Gastrointestinal adverse events ranked among the top ten System Organ Classes for all five drugs. At the pharmacovigilance level, we identified 18 positive signals, with significant risks for five specific adverse events: constipation, dry mouth, oral hypoaesthesia, nausea, and vomiting. Descriptive analyses revealed that middle-aged (45-64 years) and elderly (65-74 years) patients were more susceptible to gastrointestinal adverse events compared to younger age groups, although the specific effects varied across different drugs and age groups. These findings highlight the significant risks of gastrointestinal AEs associated with SNRIs, underscoring the need for individualized drug selection, close monitoring, and further research into underlying mechanisms and long-term impacts.

We previously reported greater reductions in depression and anxiety following probiotic supplementation in people with major depressive disorder (MDD) in a randomised double-blind placebo-controlled pilot trial (Nikolova et al., 2023). Here, we investigate the mechanisms underlying these effects.

49 people with MDD received a multi-strain probiotic (n = 24) or placebo (n = 25) for 8 weeks in addition to their antidepressant. Stool and blood samples were collected to analyse gut microbiota composition and inflammatory cytokines. Stool samples from 25 matched healthy volunteers (HVs) were also obtained.

Within the probiotic group, there was a significant increase in richness according to Chao1(bias-corrected) (w4 p = 0.04) and a trend for increased Total count (w4 p = 0.06, w8 p = 0.09) compared to baseline, but not to placebo. When compared to HVs post-treatment, only the placebo group had a significant decrease in Shannon' entropy (p = 0.03) and a trend for decreased Total count (p = 0.08) and Simpson's index (p = 0.09). Between-group differences in beta diversity were observed at week 4 (p = 0.04), but not week 8. Consistent between-group differences were seen in family Bacilleceae post-treatment (FDR p < 0.05), which correlated with decreases in anxiety (FDR p < 0.05). There were no differences in inflammatory markers.

This study was limited by data loss during the COVID-19 Pandemic.

Probiotics may positively impact the microbiota by normalising diversity and increasing levels of health-related taxa, which may partially account for their benefits in MDD. Understanding how these changes relate to symptom improvement can inform their targeted use in clinical practice. Larger trials incorporating functional multi-omics are needed.

NCT03893162.

This study explores the behavioral and molecular biological impacts of Fecal Microbiota Transplantation (FMT) on depressive mice unresponsive to treatment with Selective Serotonin Reuptake Inhibitors (SSRIs).

Healthy male C57BL/6 mice were used to establish a depression model through chronic restraint stress, treated with fluoxetine, and categorized into Response and Non-response groups. An FMT treatment was added to the Non-response group. Behavioral tests were conducted to assess symptoms of depression. The gut microbiome, plasma metabolites, and hippocampal tissue gene expression and function changes were analyzed using 16S rRNA gene sequencing, LC-MS, and RNA sequencing.

FMT significantly improved the depressive symptoms in SSRIs-resistant mice. There was a partial restoration in the diversity and structure of the gut microbiota in the FMT group. Compared to the Non-response group, significant changes were noted in the metabolomic profiles of the FMT group, identifying various differential metabolites. Functional annotations indicated that these metabolites are involved in multiple metabolic pathways. In the Non-response group, certain gene expression levels were significantly restored. GO and KEGG enrichment analyses revealed that these differential genes mainly involve cytokine activity, receptor signaling regulation, and NOD-like receptor signaling pathways. Joint analysis suggested that FMT may exert its effects through an increase in the abundance of g__Paraprevotella, leading to decreased baicalin content and increased Tal2 expression.

FMT has potential in improving depressive symptoms unresponsive to SSRIs treatment. Its mechanism may be related to the modulation of the gut microbiota and its metabolites, subsequently affecting gene expression.

The human gut flora of trillions of bacteria is vital for general health and greatly influences digestion, immune system function, and brain development. Through neuronal, hormonal, and immunological channels, the gut-brain axis (GBA), a bidirectional communication network, links the gut microbiota to the central nervous system (CNS). This relationship has been linked to affective diseases, including depression and anxiety, as well as mental health issues. This review explores the intricate relationship between gut bacteria and mood disorders, focusing on how gut microbiota-host interactions, immune system modulation, and neurotransmitter control support mental health. The function of important microbial metabolites, including short-chain fatty acids (SCFAs), in preserving blood-brain barrier integrity and modulating neuroinflammation is covered in this review. It also examines the bidirectional impact between gut health and mental health, including how dysbiosis could aggravate mood disorders and how depressed states might change the composition of gut bacteria. Furthermore, we discuss how psychotropic drugs affect gut flora and consider other elements such as nutrition and lifestyle that affect gut microbiome composition. Potential paths for treating mood disorders through gut microbiota modification are presented as emerging treatment techniques, including probiotics, nutritional therapies, and precision medicine. The development of new therapeutic approaches for mood disorders depends on the awareness of the GBA. Gut bacteria significantly affect mental health through immune modulation, neurotransmitter generation, and other intricate processes. Future studies should concentrate on large, varied populations to better understand these interactions and to create customized treatments that combine gut microbiota modulation with conventional mental health therapies.

The microbiota-gut-brain axis plays a pivotal role in neuropsychiatric disorders, particularly in depression. Escitalopram (ESC) is a first-line antidepressant, however, its regulatory mechanisms on the microbiota-gut-brain axis in the treatment of depression remain unclear. The antidepressant effects of ESC were evaluated using the forced swim test in Wistar-Kyoto (WKY) rats, while damage in the gut and brain regions was assessed through H&E staining and immunohistochemistry. The therapeutic mechanisms in WKY rats with depression-like behavior were investigated through 16S rRNA sequencing of the gut microbiota, serum untargeted metabolomics, and hippocampal proteomics. Results indicated that ESC intervention improved depressive-like behaviors, as evidenced by increased swimming times in WKY rats, and also restored intestinal permeability and brain tissue integrity. Significant changes in the gut microbiota composition, particularly an increase in Bacteroides barnesiae, as well as increases in serum sphingolipid metabolites (Sphinganine 1-phosphate, Sphingosine, and Sphingosine-1-phosphate) and hippocampal proteins (Sptlc1, Enpp5, Enpp2), were strongly correlated. These robust correlations suggest that ESC may exert its antidepressant effects by modulating sphingolipid metabolism through the influence of gut microbiota. Accordingly, this research elucidates novel mechanisms underlying the antidepressant efficacy of ESC and highlights the pivotal importance of the microbiota-gut-brain axis in mediating these effects.

There is a growing body of evidence suggesting that antidepressant drugs (ADs) alter the gut microbiome of persons with depressive disorders. Herein, we aim to investigate the gut microbial profile of AD-treated animal models of depression (MoD) and persons with major depressive disorder (MDD).

We conducted a systematic review and meta-analysis investigating the gut microbiome community-level diversity and relative abundance of microbial taxa in AD-treated animal MoD and persons with MDD.

24 human studies (898 participants) and 48 animal studies (849 subjects) were identified. Nonsignificant differences in gut microbial richness were observed between AD-treated and nonmedicated animals and humans. Beta diversity analysis in animals shows that AD intake is linked to a distinct gut microbial profile, a result not observed in humans. Consistent depletion of the genera Faecalibacterium and Parasutterella, along with enrichment of Bifidobacterium, was observed in AD-treated persons with MDD. In AD-treated animals, AD intake was associated with depletion of Flavobacterium and Adlercreutzia, and enrichment of Parabacteroides.

The studies in our review were heterogeneous in their participant population, dietary intake, type of ADs used, length and dosing of AD treatment, and frequency and time of fecal sample collection.

ADs are associated with some changes to the gut microbiome. Future studies should evaluate the gut microbiome profiles between depressive disorder diagnoses that may reveal potential differences and predictors of AD response, as well as new combinatorial therapeutics with agents (e.g., specific-strain probiotic adjunctive treatment) that can ameliorate micro-composition gut dysbiosis.

The topic of increased intestinal permeability is associated with disruption of the intestinal barrier, leading to the "leaky gut" syndrome. Depressive disorders often coexist with abdominal obesity, metabolic syndrome, or its components and complications. Intestinal permeability has been proven to relate to all of the above.

In this cross-sectional study, we aimed to assess the "leaky gut" blood biomarker - intestinal fatty acid-binding protein (I-FABP) - in 114 adult patients diagnosed with depressive disorders depending on abdominal obesity comorbidity, depression, anxiety, and stress level, or antidepressant use. The corrected p-value was set at 0.02. We analyzed patients' mental state, diet, anthropometric parameters, metabolic laboratory markers and I-FABP.

There was no difference in circulating I-FABP levels between obese and non-obese patients with depressive disorders (p = 0.648). Similarly, I-FABP levels were not different in patients with different emotional symptoms severity (p = 0.829 for self-assessed depression, p = 0.164 for anxiety, and p = 0.543 for stress). But, I-FABP levels differed significantly between patients treated and not treated with antidepressants (p = 0.011). In general linear model analysis treatment with antidepressants, anxiety severity level, their interaction, along with smoking status, drinks intake, and using dietary supplements were shown to significantly explain I-FABP variance (p < 0.001, R2adj = 0.261).

Comorbid obesity did not increase intestinal permeability circulating marker, I-FABP, in the population of patients with depressive disorders. Treatment with antidepressants may be connected to higher I-FABP levels. Using dietary supplements, drinks intake, smoking status, or anxiety level may serve as explanatory factors.

This review synthesizes the evidence on associations between antidepressant use and gut microbiota composition and function, exploring the microbiota's possible role in modulating antidepressant treatment outcomes. Antidepressants exert an influence on measures of gut microbial diversity. The most consistently reported differences were in β-diversity between those exposed to antidepressants and those not exposed, with longitudinal studies supporting a potential causal association. Compositional alterations in antidepressant users include an increase in the Bacteroidetes phylum, Christensenellaceae family, and Bacteroides and Clostridium genera, while a decrease was found in the Firmicutes phylum, Ruminococcaceae family, and Ruminococcus genus. In addition, antidepressants attenuate gut microbial differences between depressed and healthy individuals, modulate microbial serotonin transport, and influence microbiota's metabolic functions. These include lyxose degradation, peptidoglycan maturation, membrane transport, and methylerythritol phosphate pathways, alongside gamma-aminobutyric acid metabolism. Importantly, baseline increased α-diversity and abundance of the Roseburia and Faecalibacterium genera, in the Firmicutes phylum, are associated with antidepressant response, emerging as promising biomarkers. This review highlights the potential for gut microbiota as a predictor of treatment response and emphasizes the need for further research to elucidate the mechanisms underlying antidepressant-microbiota interactions. More homogeneous studies and standardized techniques are required to confirm these initial findings.

Bacterial biofilms represent a formidable challenge in the treatment of chronic wounds, largely because of their resistance to conventional antibiotics. The emergence of multidrug-resistant (MDR) bacterial strains exacerbates this issue, necessitating a shift towards exploring alternative therapeutic approaches. In response to this urgent need, there has been a surge in research efforts aimed at identifying effective non-antibiotic treatments. Recently noted among the non-antibiotic options are selective serotonin reuptake inhibitors (SSRIs) and beta-adrenergic (β-AR) antagonists. Both have demonstrated antimicrobial activities and wound-healing properties, which makes them particularly promising potential therapeutics for chronic wounds. This review seeks to comprehensively evaluate the landscape of non-antibiotic strategies for managing wound infections. By analysing the latest research findings and clinical developments, it aims to shed light on emerging therapeutic alternatives. Additionally, the review delves into the potential of repurposing systemic therapeutics for topical application, offering insights into the feasibility and challenges associated with current approaches. We also address the necessity of translating promising preclinical results into tangible clinical benefits.

Despite recent advances in antidepressants in treating major depression (MDD), their usage is marred by adverse effects and social stigmas. Probiotics may be an efficacious adjunct or standalone treatment, potentially circumventing the aforementioned issues with antidepressants. However, there is a lack of head-to-head clinical trials between these 2 interventions.

A systematic review and network meta-analysis was conducted to compare the efficacy and acceptability of these 2 interventions in treating MDD.

Six databases and registry platforms for the clinical trial were systematically searched to identify the eligible double-blinded, randomized controlled trials published between 2015 and 2022.

Two authors selected independently the placebo-controlled trials of antidepressants and microbiota-targeted interventions (prebiotics, probiotics, and synbiotics) used for the treatment of MDD in adults (≥18 years old). Standardized mean differences (SMDs) of depressive symptom scores from individual trials were pooled for network meta-analysis (PROSPERO no. CRD42020222305).

Forty-two eligible trials covering 22 interventions were identified, of which 16 were found to be effective in MDD treatment and the certainty of evidence was moderate to very low. When all trials were considered, compared with placebo, SMDs of interventions ranged from -0.16 (95% credible interval: -0.30, -0.04) for venlafaxine to -0.81 (-1.06, -0.52) for escitalopram. Probiotics were superior to brexpiprazole (SMD [95% credible interval]: -0.42 [-0.68, -0.17]), cariprazine (-0.44 [-0.69, -0.24]), citalopram (-0.37 [-0.66, -0.07]), duloxetine (-0.26, [-0.51, -0.04]), desvenlafaxine (-0.38 [-0.63, -0.14]), ketamine (-0.32 [-0.66, -0.01]), venlafaxine (-0.47 [-0.73, -0.23]), vilazodone (-0.37 [-0.61, -0.12]), vortioxetine (-0.39 [-0.63, -0.15]), and placebo (-0.62 [-0.86, -0.42]), and were noninferior to other antidepressants. In addition, probiotics ranked the second highest in the treatment hierarchy after escitalopram. Long-term treatment (≥8 weeks) using probiotics showed the same tolerability as antidepressants.

Probiotics, compared with antidepressants and placebo, may be efficacious as an adjunct or standalone therapy for treating MDD.

PROSPERO registration no. CRD42020222305.

Mood disorders include a set of psychiatric manifestations of increasing prevalence in our society, being mainly represented by major depressive disorder (MDD) and bipolar disorder (BD). The etiopathogenesis of mood disorders is extremely complex, with a wide spectrum of biological, psychological, and sociocultural factors being responsible for their appearance and development. In this sense, immune system dysfunction represents a key mechanism in the onset and pathophysiology of mood disorders, worsening mainly the central nervous system (neuroinflammation) and the periphery of the body (systemic inflammation). However, these alterations cannot be understood separately, but as part of a complex picture in which different factors and systems interact with each other. Psychoneuroimmunoendocrinology (PNIE) is the area responsible for studying the relationship between these elements and the impact of mind-body integration, placing the immune system as part of a whole. Thus, the dysfunction of the immune system is capable of influencing and activating different mechanisms that promote disruption of the psyche, damage to the nervous system, alterations to the endocrine and metabolic systems, and disruption of the microbiota and intestinal ecosystem, as well as of other organs and, in turn, all these mechanisms are responsible for inducing and enhancing the immune dysfunction. Similarly, the clinical approach to these patients is usually multidisciplinary, and the therapeutic arsenal includes different pharmacological (for example, antidepressants, antipsychotics, and lithium) and non-pharmacological (i.e., psychotherapy, lifestyle, and electroconvulsive therapy) treatments. These interventions also modulate the immune system and other elements of the PNIE in these patients, which may be interesting to understand the therapeutic success or failure of these approaches. In this sense, this review aims to delve into the relationship between immune dysfunction and mood disorders and their integration in the complex context of PNIE. Likewise, an attempt will be made to explore the effects on the immune system of different strategies available in the clinical approach to these patients, in order to identify the mechanisms described and their possible uses as biomarkers.

Patients with inflammatory bowel diseases (IBDs) are more likely to have depression and anxiety symptoms compared with healthy individuals and those with other chronic illnesses. Previous studies have shown a link between the microbiome composition and depression symptoms; however, many antidepressant medications have antibacterial activity confounding cross-sectional studies of these populations. Therefore, we aimed to determine whether we could detect longitudinal changes in the microbiome of a subset of patients who participated in a previously published mindfulness-based cognitive therapy (MBCT) study to improve depression symptoms in adolescents and young adults with IBD.

Stool samples were collected at baseline and 8 weeks (n = 24 participants, 37 total samples, 13 paired samples). During this time, some participants achieved a 50% reduction in their depression symptoms either through MBCT or treatment as usual with their mental health team (responders). The microbiome composition and function of responders were compared with participants who did not improve their depression scores (nonresponders). Depression scores were determined using the depression, anxiety, and stress score (DASS-21), and metagenomic sequencing of stool samples was performed.

No difference in alpha diversity was found between responders and nonresponders. Beta diversity measures were similarly unchanged. Clinical features including fecal calprotectin, C-reactive protein, and serum IL-6 levels were unchanged.

In this small longitudinal study, we were not able to detect longitudinal changes in the microbiome associated with improvement in depression scores. Follow-up studies that are sufficiently powered to detect changes in the microbiome are required to confirm our results.

This paper explores the intricate relationship between depression, gut dysbiosis, and Clostridioides difficile infections, collectively termed "The 3 Ds". Depression is a widespread mental disorder increasing in prevalence. It is recognized for its societal burden and complex pathophysiology, encompassing genetic, environmental, and microbiome-related factors. The consequent increased use of antidepressants has led to growing concerns about their effects on the gut microbiome. Various classes of antidepressants and antipsychotics show antimicrobial activity, potentially leading to shifts in the gut microbiome and contributing to the development of dysbiosis. Dysbiosis, in turn, can predispose individuals to opportunistic infections like C. difficile, a significant healthcare concern due to its high recurrence rates and severe impact on patients' quality of life. Further, the link between antidepressant use and an increased risk of C. difficile infection (CDI) is explored and, finally, the emergence of live biotherapeutic products as novel treatment options for recurrent CDI is discussed.

The relationship between depression and gut microbiota remains unclear, but an important role of gut microbiota has been verified. The relationship between gut microbiota and antibiotic resistance genes (ARGs) may be a potential new explanatory pathway.

We collected samples from 63 depressed patients and 30 healthy controls for metagenomic sequencing. The two groups' microbiota characteristics, functional characteristics, and ARG differences were analyzed.

We obtained 30 differential KEGG orthologs (KOs) and their producers in 5 genera and 7 species by HUMAnN3. We found 6 KOs from Weissella_cibaria and Lactobacillus_plantaru are potentially coring functional mechanism of gut microbiota. Different metabolites including sphingolipids, pyrans, prenol lipids, and isoflavonoids also showed significance between MDD and HC. We detected 48 significantly different ARGs: 5 ARGs up-regulated and 43 ARGs down-regulated in MDD compared to HC. Based on Cox model results, Three ARGs significantly affected drug efficacy (ARG29, ARG105, and ARG111). Eggerthella, Weissella, and Lactobacillus were correlated with different core ARGs, which indicated different mechanisms in affecting MDD.

The present study needs to be replicated in different ethnic groups. At the same time, a larger Chinese cohort study and detailed experimental verification are also the key to further discussion.

Our findings suggest that ARGs play a role in the interplay between major depressive disorder and gut microbiota. The role of ARGs should be taken into account when understanding the relationship between depression and gut microbiota.

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.

The role of the gut microbiota in the pathophysiology of depression has been explored in numerous studies, which have confirmed that the baseline gut microbial profiles of patients with depression differ from those of healthy individuals. The gut microbiome affects metabolic activity in the immune and central nervous systems and regulates intestinal ecology through the neuroendocrine system. Additionally, baseline changes in the gut microbiota differed among patients with depression who demonstrated varying treatment response. Currently, probiotics are an emerging treatment for depression; however, the efficacy of modulating the gut microbiota in the treatment of depression remains uncertain. Additionally, the mechanisms by which changes in the gut microbiota affect treatment response in patients with depression remain unclear. In this review, we aimed to summarize the differences in the baseline gut microbiota between the remission and non-remission groups after antidepressant therapy. Additionally, we summarized the possible mechanisms that may contribute to antidepressant resistance through the effects of the gut microbiome on the immune and nervous systems, various enzymes, bioaccumulation, and blood-brain barrier, and provide a basis for treating depression by targeting the gut microbiota.

Selective Serotonin Reuptake Inhibitor (SSRI) therapy is common among perinatal populations for the treatment of mood disorders. Medications can affect diversity and composition of the gut microbiome, which plays a key role in modulating health. While previous studies have examined the effects of antidepressant exposure on the maternal gut microbiome, whether SSRI exposure affects the offspring gut microbiome is unknown. We investigated the effects of maternal fluoxetine exposure on the gut microbiome of maternal and offspring mice during pregnancy and lactation (embryonic day 10-lactation day 21; E10-L21). Stool samples collected on E17, L11, L15, and L21 were examined using 16S rRNA sequencing. Our results suggest that maternal fluoxetine exposure may result in decreased alpha diversity of the offspring gut microbiome in early life. Furthermore, we observed several genera-specific differences in the gut microbiome based on treatment, specifically of Turicibacter, Parasutterella, and Romboutsia. These findings support our understanding of gut health, as dysbiotic development of the gut microbiome has been associated with local and systemic health problems including gastrointestinal morbidities and interrupted growth patterns in infants. Future research should pursue study in human populations and those at high risk for gut microbial dysbiosis and intestinal injury.

Preclinical studies suggested that drugs that functionally inhibit acid sphingomyelinase (FIASMA)may enhance immune cell longevity and potentially offer protection against infections. Many antidepressants have shown FIASMA activity.

We conducted a cohort study using primary-care data from the UK-based Clinical Practice Research Datalink (2000-2021). We assessed the association of composite diagnosed acute infections in new users of fluoxetine, sertraline, paroxetine, or venlafaxine aged 18-80 years compared to citalopram. We compared SARS-CoV-2 infections between groups in a secondary analysis. We estimated incidence rates (IR) and IR ratios (IRR) of acute infections in four pairwise comparisons using negative binomial regression. We applied propensity score (PS) fine stratification to control for confounding.

In the PS-weighted cohorts, we included 353,138 fluoxetine, 222,463 sertraline, 69,963 paroxetine, 32,608 venlafaxine, and between 515,996 and 516,583 new citalopram users. PS-weighted IRs ranged between 76.8 acute infections /1000 person-years (py) (sertraline) and 98.9 infections/1000 py (citalopram). We observed PS-weighted IRRs around unity for paroxetine (0.97, 95 % CI, 0.95-1.00), fluoxetine (0.94, 95 % CI, 0.92-0.95), and venlafaxine (0.90, 95 % CI, 0.87-0.94) vs citalopram. Reduced IRR for sertraline vs citalopram (0.84, 95 % CI, 0.82-0.85), became null within subgroups by cohort entry date. In the analysis of SARS-CoV-2 infection, no statistically relevant risk reduction was seen.

Analysis not limited to patients with diagnosed depression, possible underestimation of infection incidence, and unclear FIASMA activity of citalopram.

Fluoxetine, sertraline, paroxetine, and venlafaxine were not associated with a reduced risk of acute infection when compared with the presumably weak FIASMA citalopram.

Electroacupuncture (EA) is a neuroregulatory therapy for depression. Nonetheless, the effects of EA on the gut microbiome in mice models of depression are not well established. Here, using a chronic unpredictable mild stress (CUMS) model in mice, we evaluated the antidepressant effects of EA and changes in gut microbiota with behavioral tests and 16S rRNA gene sequencing. The results found that EA increased the time spent in the center area of the open-field test and the percentage of sucrose preference and reduced the immobility time in the tail suspension test in CUMS-treated mice. Furthermore, the genus Lachnoclostridium, Ruminococcaceae_UCG-002 and Rikenellaceae_RC9_gut_group were enriched in the CUMS group, which was positively correlated with depressive-like behaviors. Whereas phylum Actinobacteria and genus Allobaculum, Bifidobacterium, Dubosiella, Rikenella and Ileibacterium were enriched in the EA and CUMS + EA groups, all of which were negatively correlated with depressive-like behaviors. This study characterizes gut microbiota under EA treatment and provides new insights into the association of anti-depressive-like effects of EA and gut microbiota.

The aims of this study were to design a novel titanium surface coated with a PVA hydrogel matrix and chitosan-based nanoparticles and to investigate the antibiotic release and its ability to inhibit microbial activity.

Two drug delivery systems were developed and mixed. Chitosan-based nanoparticles (NP) and a polyvinyl alcohol film (PVA). The size, ζ-potential, stability, adhesive properties, and encapsulation profile of NP, as well as the release kinetics of drug delivery systems and their antimicrobial ability of PVA and PVANP films, were studied on Ti surfaces. The systems were loaded with doxycycline, vancomycin, and doxepin hydrochloride.

Nanoparticles presented a ζ-potential greater than 30 mV for 45 days and the efficiency drug encapsulation was 26.88% ± 1.51% for doxycycline, 16.09% ± 10.24% for vancomycin and 17.57% ± 11.08% for doxepin. In addition, PVA films were loaded with 125 μg/mL of doxycycline, 125 μg/mL of vancomycin, and 100 μg/mL of doxepin. PVANP-doxycycline achieved the antibacterial effect at 4 h while PVA-doxycycline maintained its effect at 24 h.

Psychiatric disorders represent a primary source of disability worldwide, manifesting as disturbances in individuals' cognitive processes, emotional regulation, and behavioral patterns. In the quest to discover novel therapies and expand the boundaries of neuropharmacology, studies from the field have highlighted the gut microbiota's role in modulating these disorders. These alterations may influence the brain's processes through the brain-gut axis, a multifaceted bidirectional system that establishes a connection between the enteric and central nervous systems. Thus, probiotic and prebiotic supplements that are meant to influence overall gut health may play an insightful role in alleviating psychiatric symptoms, such as the cognitive templates of major depressive disorder, anxiety, or schizophrenia. Moreover, the administration of psychotropic drugs has been revealed to induce specific changes in a microbiome's diversity, suggesting their potential utility in combating bacterial infections. This review emphasizes the intricate correlations between psychiatric disorders and the gut microbiota, mentioning the promising approaches in regard to the modulation of probiotic and prebiotic treatments, as well as the antimicrobial effects of psychotropic medication.

Alterations in gut microbiota composition have been associated with several conditions, and there is emerging evidence that sleep quantity and quality are associated with the composition of the gut microbiome. Therefore, this study aimed to assess the associations between several measures of sleep and the gut microbiome in a large, population-based sample.

Data were collected from participants in the Survey of the Health of Wisconsin from 2016 to 2017 (N = 720). Alpha diversity was estimated using Chao1 richness, Shannon's diversity, and Inverse Simpson's diversity. Beta diversity was estimated using Bray-Curtis dissimilarity. Models for each of the alpha-diversity outcomes were calculated using linear mixed effects models. Permutational multivariate analysis of variance tests were performed to test whether gut microbiome composition differed by sleep measures. Negative binomial models were used to assess whether sleep measures were associated with individual taxa relative abundance.

Participants were a mean (SD) age of 55 (16) years and 58% were female. The sample was 83% non-Hispanic white, 10.6% non-Hispanic black, and 3.5% Hispanic. Greater actigraphy-measured night-to-night sleep duration variability, wake-after-sleep onset, lower sleep efficiency, and worse self-reported sleep quality were associated with lower microbiome richness and diversity. Sleep variables were associated with beta-diversity, including actigraphy-measured night-to-night sleep duration variability, sleep latency and efficiency, and self-reported sleep quality, sleep apnea, and napping. Relative abundance of several taxa was associated with night-to-night sleep duration variability, average sleep latency and sleep efficiency, and sleep quality.

This study suggests that sleep may be associated with the composition of the gut microbiome. These results contribute to the body of evidence that modifiable health habits can influence the human gut microbiome.

The gut microbiome is emerging as an important factor in signaling along the gut-brain axis. The intimate physiological connection between the gut and the brain allows perturbations in the microbiome to be directly transmitted to the central nervous system and thereby contribute to psychiatric and neurological diseases. Common microbiome perturbations result from the ingestion of xenobiotic compounds including pharmaceuticals such as psychotropic drugs. In recent years, a variety of interactions between these drug classes and the gut microbiome have been reported, ranging from direct inhibitory effects on gut bacteria to microbiome-mediated drug degradation or sequestration. Consequently, the microbiome may play a critical role in influencing the intensity, duration, and onset of therapeutic effects, as well as in influencing the side effects that patients may experience. Furthermore, because the composition of the microbiome varies from person to person, the microbiome may contribute to the frequently observed interpersonal differences in the response to these drugs. In this review, we first summarize the known interactions between xenobiotics and the gut microbiome. Then, for psychopharmaceuticals, we address the question of whether these interactions with gut bacteria are irrelevant for the host (i.e., merely confounding factors in metagenomic analyses) or whether they may even have therapeutic or adverse effects.

The link between drug-induced dysbiosis and its influence on brain diseases through gut-residing bacteria and their metabolites, named the microbiota-gut-brain axis (MGBA), remains largely unexplored. This review investigates the effects of commonly prescribed drugs (metformin, statins, proton-pump-inhibitors, NSAIDs, and anti-depressants) on the gut microbiota, comparing the findings with altered bacterial populations in major brain diseases (depression, multiple sclerosis, Parkinson's and Alzheimer's). The report aims to explore whether drugs can influence the development and progression of brain diseases via the MGBA. Central findings indicate that all explored drugs induce dysbiosis. These dysbiosis patterns were associated with brain disorders. The influence on brain diseases varied across different bacterial taxa, possibly mediated by direct effects or through bacterial metabolites. Each drug induced both positive and negative changes in the abundance of bacteria, indicating a counterbalancing effect. Moreover, the above-mentioned drugs exhibited similar effects, suggesting that they may counteract or enhance each other's effects on brain diseases when taken together by comorbid patients. In conclusion, the interplay of bacterial species and their abundances may have a greater impact on brain diseases than individual drugs or bacterial strains. Future research is needed to better understand drug-induced dysbiosis and the implications for brain disease pathogenesis, with the potential to develop more effective therapeutic options for patients with brain-related diseases.

Functional gastrointestinal disorders (FGIDs), chronic disorders characterized by either abdominal pain, altered intestinal motility, or their combination, have a worldwide prevalence of more than 40% and impose a high socioeconomic burden with a significant decline in quality of life. Recently, FGIDs have been reclassified as disorders of gut-brain interaction (DGBI), reflecting the key role of the gut-brain bidirectional communication in these disorders and their impact on psychological comorbidities. Although, during the past decades, the field of DGBIs has advanced significantly, the molecular mechanisms underlying DGBIs pathogenesis and pathophysiology, and the role of the gut microbiome in these processes are not fully understood. This review aims to discuss the latest body of literature on the complex microbiota-gut-brain interactions and their implications in the pathogenesis of DGBIs. A better understanding of the existing communication pathways between the gut microbiome and the brain holds promise in developing effective therapeutic interventions for DGBIs.

Antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are commonly prescribed for depression treatment. Animal studies have shown that antidepressants can influence gut microbiota composition and specific bacterial taxa. We aimed to investigate the association between antidepressant use and human gut microbiota composition and functional pathway.

We collected information on antidepressant use, demographic, food patterns, and clinical characteristics through questionnaires and medical records. The gut microbiota profiles of 271 depressive patients were carried out through 16S rRNA gene sequencing. Patients were categorized based on different types of antidepressant use groups for gut microbiota comparisons. MaAsLin2 was performed to evaluate microbiota composition across groups. PICRUSt2 was used to predict microbiota functional pathways.

Patients taking SSRIs or SNRIs had a lower microbiota diversity. We found seven taxa abundances (Turicibacter, Barnesiella, Lachnospiraceae_ND3007_group, Romboutia, Akkermansia, Dialister, Romboutia and Fusicatenibacter) differed in patients with various types of antidepressants compared with those without antidepressant treatments (p < 0.05). Turicibacter inversely correlated with depression severity in SSRIs or SNRI users (r = -0.43, p < 0.05). Top identified pathways were related to compound fermentation and biosynthesis in microbiota function.

Antidepressant usage, especially SSRIs and SNRIs, associates with changes in gut microbiota composition and specific taxa. Given our study's preliminary cross-sectional nature, further research is warranted to comprehend the relationship between antidepressant use, treatment response, and gut microbiota, aiming to enhance therapeutic interventions in the future.

The mammalian gut contains a community of microorganisms called gut microbiome. The gut microbiome is integrated into mammalian physiology, contributing to metabolism, production of metabolites, and promoting immunomodulatory actions. Microglia, the brain's resident innate immune cells, play an essential role in homeostatic neurogenesis, synaptic remodeling, and glial maturation. Microglial dysfunction has been implicated in the pathogenesis of several neuropsychiatric disorders. Recent findings indicate that microglia are influenced by the gut microbiome and their derived metabolites throughout life. The pathways by which microbiota regulate microglia have only started to be understood, but this discovery has the potential to provide valuable insights into the pathogenesis of brain disorders associated with an altered microbiome. Here, we discuss the recent literature on the role of the gut microbiome in modulating microglia during development and adulthood and summarize the key findings on this bidirectional crosstalk in selected examples of neuropsychiatric and neurodegenerative disorders. We also highlight some current caveats and perspectives for the field.

Major depressive disorder (MDD) is a common neuropsychiatric challenge that primarily targets young females. MDD as a global disorder has a multifactorial etiology related to the environment and genetic background. A balanced gut microbiota is one of the most important environmental factors involved in human physiological health. The interaction of gut microbiota components and metabolic products with the hypothalamic-pituitary-adrenal system and immune mediators can reverse depression phenotypes in vulnerable individuals. Therefore, abnormalities in the quantitative and qualitative structure of the gut microbiota may lead to the progression of MDD. In this review, we have presented an overview of the bidirectional relationship between gut microbiota and MDD, and the effect of pre-treatments and microbiomebased approaches, such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and a new generation of microbial alternatives, on the improvement of unstable clinical conditions caused by MDD.

Previous studies have reported a variety of gut microbiota alterations in patients with schizophrenia. However, none of these studies has investigated gut microbiota in patients with the deficit subtype of schizophrenia (D-SCZ) that can be characterized by primary and enduring negative symptoms. Therefore, in this study we aimed to profile gut microbiota of individuals with D-SCZ, compared to those with non-deficit schizophrenia (ND-SCZ) and healthy controls (HCs).

A total of 115 outpatients (44 individuals with D-SCZ and 71 individuals with ND-SCZ) during remission of positive and disorganization symptoms as well as 120 HCs were enrolled. Gut microbiota was analyzed using the 16 rRNA amplicon sequencing. Additionally, the levels of C-reactive protein (CRP), glucose and lipid metabolism markers were determined in the peripheral blood samples.

Altogether 14 genera showed differential abundance in patients with D-SCZ compared to ND-SCZ and HCs, including Candidatus Soleaferrea, Eubacterium, Fusobacterium, Lachnospiraceae UCG-002, Lachnospiraceae UCG-004, Lachnospiraceae UCG-010, Libanicoccus, Limosilactobacillus, Mogibacterium, Peptococcus, Prevotella, Prevotellaceae NK3B31 group, Rikenellaceae RC9 gut group, and Slackia after adjustment for potential confounding factors. Observed alterations were significantly associated with cognitive performance in both groups of patients. Moreover, several significant correlations of differentially abundant genera with the levels of CRP, lipid profile parameters, glucose and insulin were found across all subgroups of participants.

Findings from the present study indicate that individuals with D-SCZ show a distinct profile of gut microbiota alterations that is associated with cognitive performance, metabolic parameters and subclinical inflammation.

Microorganisms have a close relationship with humans, whether it is commensal, symbiotic, or pathogenic. Recently, it has been documented that microorganisms may influence the response to drug therapy. Pharmacomicrobiomics is an emerging field that focuses on the study of how variations in the microbiome affect the disposition, action, and toxicity of drugs. Two additional sciences have been added to complement pharmacomicrobiomics, namely toxicomicrobiomics, which explores how the microbiome influences drug metabolism and toxicity, and pharmacoecology, which refers to modifications in the microbiome as a result of drug administration. In this context, we introduce the concept of "drug-infection interaction" to describe the influence of pathogenic microorganisms on drug response. This review analyzes the current state of knowledge regarding the relevance of microorganisms in the host's response to drugs. It also highlights promising areas for future research and proposes the term "drug-infection interaction" as an extension of pharmacomicrobiomics.

The gut microbiome is involved in the bi-directional relationship of the gut - brain axis. As most studies of this relationship are small and do not account for use of psychotropic drugs (PTDs), we explored the relations of the gut microbiome with several internalizing disorders, while adjusting for PTDs and other relevant medications, in 7,656 Lifelines participants from the Northern Netherlands (5,522 controls and 491 participants with at least one internalizing disorder). Disorders included dysthymia, major depressive disorder (MDD), any depressive disorder (AnyDep: dysthymia or MDD), generalized anxiety disorder (GAD) and any anxiety disorder (AnyAnx: GAD, social phobia and panic disorder). Compared to controls, 17 species were associated with depressive disorders and 3 were associated with anxiety disorders. Around 90% of these associations remained significant (FDR <0.05) after adjustment for PTD use, suggesting that the disorders, not PTD use, drove these associations. Negative associations were observed for the butyrate-producing bacteria Ruminococcus bromii in participants with AnyDep and for Bifidobacterium bifidum in AnyAnx participants, along with many others. Tryptophan and glutamate synthesis modules and the 3,4-Dihydroxyphenylacetic acid synthesis module (related to dopamine metabolism) were negatively associated with MDD and/or dysthymia. After additional adjustment for functional gastrointestinal disorders and irritable bowel syndrome, these relations remained either statistically (FDR <0.05) or nominally (P < 0.05) significant. Overall, multiple bacterial species and functional modules were associated with internalizing disorders, including gut - brain relevant components, while associations to PTD use were moderate. These findings suggest that internalizing disorders rather than PTDs are associated with gut microbiome differences relative to controls.

Depressive Disorders in Adolescence: Current State of Studies Concerning the Microbiota-Gut-Brain Axis Abstract. Depressive disorders increase during adolescence and often lead to significant impairment in affected individuals - despite treatment. Current research efforts aim to further investigate the pathophysiology of depression, considering the influence of gut microbiota on the gut-brain axis. The present narrative review outlines the current state of studies of the microbiota-gut-brain axis in depressive disorders as well as the direct and indirect interactions in adolescence. Besides providing promising results from animal studies, studies on the microbiota-gut-brain axis in adults suffering from depressive disorders are growing steadily. In depressed adolescents, however, the study situation is still marginal, making a recommendation for the supplementation of probiotics and prebiotics in depressed children and adolescents impossible according to the current state of research. Against the background of a very limited number of studies involving adolescents with depressive disorders, the interactive role of the microbiota-gut-brain axis in adolescent development should receive special attention in future research projects.

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.

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.

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.

These findings revealed that the modulation of gut microbiotas and PUFAs metabolism might partly contribute to the antidepressant effect of rTMS.

The trillions of microorganisms that comprise the gut microbiome form dynamic bidirectional interactions with orally administered drugs and host health. These relationships can alter all aspects of drug pharmacokinetics and pharmacodynamics (PK/PD); thus, there is a desire to control these interactions to maximize therapeutic efficacy. Attempts to modulate drug-gut microbiome interactions have spurred advancements within the field of 'pharmacomicrobiomics' and are poised to become the next frontier of oral drug delivery.

This review details the bidirectional interactions that exist between oral drugs and the gut microbiome, with clinically relevant case examples outlining a clear motive for controlling pharmacomicrobiomic interactions. Specific focus is attributed to novel and advanced strategies that have demonstrated success in mediating drug-gut microbiome interactions.

Co-administration of gut-active supplements (e.g. pro- and pre-biotics), innovative drug delivery vehicles, and strategic polypharmacy serve as the most promising and clinically viable approaches for controlling pharmacomicrobiomic interactions. Targeting the gut microbiome through these strategies presents new opportunities for improving therapeutic efficacy by precisely mediating PK/PD, while mitigating metabolic disturbances caused by drug-induced gut dysbiosis. However, successfully translating preclinical potential into clinical outcomes relies on overcoming key challenges related to interindividual variability in microbiome composition and study design parameters.

Bipolar disorders (BD) represent a severe leading disabling mental condition worldwide characterized by episodic and often progressive mood fluctuations with manic and depressive stages. The biological mechanisms underlying the pathophysiology of BD remain incompletely understood, but it seems that there is a complex picture of genetic and environmental factors implicated. Nowadays, gut microbiota is in the spotlight of new research related to this kind of psychiatric disorder, as it can be consistently related to several pathophysiological events observed in BD. In the context of the so-called microbiota-gut-brain (MGB) axis, it is shown to have a strong influence on host neuromodulation and endocrine functions (i.e., controlling the synthesis of neurotransmitters like serotonin or mediating the activation of the hypothalamic-pituitary-adrenal axis), as well as in modulation of host immune responses, critically regulating intestinal, systemic and brain inflammation (neuroinflammation). The present review aims to elucidate pathophysiological mechanisms derived from the MGB axis disruption and possible therapeutic approaches mainly focusing on gut microbiota in the complex network of BD. Understanding the mechanisms of gut microbiota and its bidirectional communication with the immune and other systems can shed light on the discovery of new therapies for improving the clinical management of these patients. Besides, the effect of psychiatric drugs on gut microbiota currently used in BD patients, together with new therapeutical approaches targeting this ecosystem (dietary patterns, probiotics, prebiotics, and other novelties) will also be contemplated.