In addition to the high neurotoxicity, depression, and anxiety are the most prominent characteristics of methamphetamine (Meth) withdrawal. Studies to date on the issue of Meth-associated depression and anxiety are focused on the brain, however, whether peripheral homeostasis, especially the "microbiota-gut" axis participates in these adverse outcomes, remains poorly understood. In the current study, with the fecal microbiota transplantation (FMT) assay, the mice received microbiota from Meth withdrawal mice displayed marked depression and anxiety behaviors. The 16S rRNA sequencing results showed that Meth withdrawal contributed to a striking reduction of Akkermansia, Bacteroides, Faecalibaculum, Desulfovibrio, and Anaerostipes, which are known to be associated with tryptophan (TRP) metabolism. Noteworthily, the substantial decreases of the indole derivatives from the TRP metabolic pathway, including IAA, IPA, ILA, IET, IArA, IAld, and TRM were observed in the serum of both Meth abusing humans and mice during Meth withdrawal with the UHPLC-MS/MS analysis. Combining the high and low TRP diet mouse model, the mice with high TRP diet obviously impeded Meth-associated depression and anxiety behaviors, and these results were further strengthened by the evidence that administration of IPA, IAA, and indole dramatically ameliorated the Meth induced aberrant behaviors. Importantly, these protective effects were remarkably counteracted in aryl hydrocarbon receptor knockout (AhR KO) mice, underlining the key roles of microbiota-indoles-AhR signaling in Meth-associated depression and anxiety. Collectively, the important contribution of the present work is that we provide the first evidence that peripheral gut homeostasis disturbance but not limited to the brain, plays a key role in driving the Meth-induced depression and anxiety in the periods of withdrawal, especially the microbiota and the indole metabolic disturbance. Therefore, targeting AhR may provide novel insight into the therapeutic strategies for Meth-associated psychological disorders.

Binge-eating spectrum disorders, including bulimia nervosa (BN) and binge-eating disorder (BED), have psychological, behavioral, and physical effects, which present significant challenges for accurate diagnosis and treatment. Identifying biomarkers is thus of relevance to improve diagnostic and treatment strategies.

Saliva collected from female individuals with BED (n = 20), BN (n = 17), and normal weight healthy controls (NW-HC) (n = 20) was analyzed to assess salivary microbiome, exosomal miRNA expression, and DNA methylation of dopaminergic system gene components.

Microbial diversity was significantly reduced in BED and BN groups compared to NW-HC. Differential abundance analysis revealed that Bacilli (class-level) were enriched in BN and BED, while Lachnospirales (order-level) were significantly depleted in BN compared to NW-HC. In total, 79 miRNAs were differentially expressed in patients compared with controls. Alteration in four of these miRNAs (let-7b-5p, mir-15b-5p, mir-429, and mir-221-3p) identified via network analysis as potentially relevant to psychiatric disorders, were confirmed to be significantly upregulated in both BED and BN compared with controls. Significant hypomethylation at specific CpG sites of the DAT1 gene was also observed in BED and BN groups relative to controls. Correlation analysis highlighted significant associations between specific microbiota genera, miRNA expression, and DNA methylation of DAT1 in both the BED and BN groups.

Our findings provide new evidence on the role of epigenetic modifications linked to alterations in salivary microbial composition and diversity in BED and BN, opening new avenues for future research and therapeutic interventions in eating disorders targeting miRNAs and microbiota.

This study aims to systematically review evidence on gut microbiota-based interventions for reducing depression- and anxiety-like symptoms in children and adolescents with autism spectrum disorder, irritable bowel syndrome, Prader-Willi syndrome, below-average literacy skills or anorexia nervosa, where some individuals may exhibit indicators of depression or anxiety. This review includes evaluated evidence from randomized controlled trials (RCTs) involving children and adolescents aged 3-19 years, identified from PsycINFO, Medline (Ovid version), Web of Science, and the reference lists of existing reviews. Risk of bias were assessed using Risk of Bias Tool (RoB 2) in RevMan (version 5.4, Cochrane Collaboration). The results were qualitatively summarized by describing the main findings across the studies. Of the 1561 studies screened, 10 RCTs with 408 participants were included. Three gut microbiota-based interventions evaluated were probiotics, prebiotics, and dietary supplementation. Probiotics and dietary supplementation were identified as effective on reducing depression and anxiety in three studies; no significant effects were reported in the remaining seven studies. No evidence supported the effectiveness of prebiotics in reducing depression and anxiety in children and adolescents. Four studies presented low risk of bias, while others showed some bias in the randomization process, allocation concealment, selective reporting, and blinding of the outcome assessment. This review highlights the potential of probiotics and dietary supplements in treating depression and anxiety in children and adolescents. However, the current evidence is constrained by inadequate mental health measurements, participant heterogeneity, and small sample sizes in reviewed studies. Further well-designed studies are needed to confirm their effectiveness.

Lead is highly toxic to the developing brain. Given its persistence in the environment, new intervention strategies are needed to mitigate the impacts of lead on child neurodevelopment. The gut microbiome, referring to the bacteria and microorganisms residing in the gastrointestinal system, may be a viable target for intervention. This short review summarizes recent evidence linking the gut-brain axis to child developmental outcomes. We explore how lead-induced effects to the gut microbiome could indirectly affect child neurodevelopment, such that disrupting or offsetting this mediating process could buffer the effects of lead on child developmental outcomes. Unexpected findings with respect to child microbiota diversity and child cognitive and behavioral outcomes as well as lead exposure and adult microbiota diversity are discussed. When possible, we draw connections between observed changes to relative bacterial abundance, proposed bacterial functions, and downstream effects to brain development. We also explore how the gut microbiome might modify the toxicity of lead by impeding the uptake of lead across the gastrointestinal tract or through indirect mechanisms in such ways that the gut microbiome does not fit within a mediating pathway. In this case, promoting the buffering capacity of the gut microbiome may reduce the impacts of lead on child neurodevelopment. The goal of this short review is to bring attention to the potential role of the gut microbiome in the associations between lead exposure and child neurodevelopment with an eye towards intervention.

Cancer patients often suffer from depression, the presence of which promotes the deterioration of the cancer patient's condition and thus affects the patient's survival. However, the exact mechanisms underlying the relationship between depression and tumour progression remain unclear, and this complexity involves multi-system and multi-level interactions, with several key challenges remaining in current research. First, the extreme complexity of biological systems. Depression and tumors involve multiple pathways such as neuroendocrine, immune system, and metabolism, respectively, and there are nonlinear interactions between these pathways (e.g., HPA axis activation affects both immunosuppression and tumor angiogenesis), so it is difficult to isolate the predominant role of a single mechanism, and there are feedback loops (e.g., inflammatory factors (e.g., IL-6) can both induce depressive symptoms and promote tumor growth) form a "feedback loop between depression and tumors" that makes it difficult to determine the direction of causality. Second, the potential blind spot of mechanism research. There is insufficient direct evidence for the brain-tumor axis, and it is known that the vagus nerve or sympathetic nerves can directly modulate the tumor microenvironment (TME) (e.g., via β-adrenergic receptors), but there is a lack of technical support for in vivo imaging on how the CNS remotely affects tumors through the neural circuits; whereas depression-associated disturbances of the intestinal flora or in certain stages of tumor development (e.g., metastatic) or specific microenvironments (e.g., areas of hyper-infiltrating T-cells) may have long-term effects on the tumors, but such changes are difficult to capture in short-term experiments and cannot be precisely temporally resolved by existing technologies. However, there are limitations in current research methods. Existing studies have relied on mouse models of chronic stress (e.g., chronic unpredictable stress), but the "depression-like behaviour" of mice is fundamentally different from the clinical manifestations of depression in humans, and the TME (e.g., immune composition) is different from that of humans. Finally, for patients with cancer-associated depression, clinical treatment is usually a two-pronged strategy, but the combination of anticancer and antidepressant drugs has limitations, such as drug-drug interactions, safety issues, and the challenge of individualised treatment in clinical practice. Therefore, by elucidating the relationship between depression and tumour bidirectional effects, this review relatively clarifies how depression affects TME to promote tumour progression by influencing changes in immunosuppression, hormonal changes, glutamate/glutamate receptors, and intestinal flora. Further, some potential therapeutic strategies are proposed for the clinical treatment of this group of patients through the above pathological mechanism; at the same time, it was found that antidepressant drugs have potential antitumor activity, and their dual pharmacological effects may provide synergistic therapeutic benefits for patients with cancer-associated depressive disorders. This finding not only expands the choice of drugs for tumour therapy but also provides a new theoretical basis for comprehensive treatment strategies in the field of psycho-oncology.

Recent research has extensively explored the involvement of gut microbes in various fatty acid metabolic processes, elucidating their crucial roles in host energy homeostasis and metabolism. Nevertheless, there remains a dearth of studies examining the comprehensive profile of fatty acid metabolites in schizophrenia and their potential connection to gut microbes.

Conducting a thorough investigation, this study scrutinized the gut microbiome composition of 63 individuals, consisting of 35 schizophrenia (SZ) patients and 28 demographically matched healthy control (HC) subjects. Feces and serum samples were meticulously collected, with stool samples subjected to 16S rRNA sequencing targeting region V4 and untargeted metabolomics analysis, while serum samples underwent untargeted metabolomics assessment.

A total of 21 different genus-level species were identified in the SZ and HC groups. Predictive analysis of gut flora pathways revealed abnormal fatty acid degradation in schizophrenia. Notably, 17 differential fatty acid metabolites were found in feces, whereas 43 were found in serum fatty acid metabolites. A higher proportion of differential fatty acid metabolites were found in serum compared to those in feces. The predominant pathways enriched in fatty acid metabolites included biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, and linoleic acid metabolism. Additionally, a significant correlation was noted between intestinal flora and fatty acids, as well as potential interactions between intestinal flora, fecal fatty acids and serum fatty acids.

Our multi-omics study provides new insights into the pathogenesis of schizophrenia, which may inform the treatment of neurodevelopmental disorders by modifying fatty acid metabolism through modulation of the gut microbiota.

The aim of this study is to investigate the characteristics of gut microbiota in depression and anxiety through a systematic review.

Articles were searched in the PubMed, Embase, and PsycINFO databases from their inception to February 12th, 2023. Case-control studies on the characteristics of gut microbiota in depression and anxiety were included. Methodological quality assessment of included studies was performed using the Newcastle-Ottawa Scale (NOS). A qualitative synthesis was conducted to assess bacterial diversity (α- and β-diversity) and taxa abundance differences at the phylum, family, and genus levels.

A total of 24 articles were included in the systematic review, 20 studies were conducted in China. Our results showed that the findings of the α- and β-diversity assessments were inconsistent for both depression and anxiety. In gut microbiota composition, we found that depression and anxiety were characterized by an enrichment of pro-inflammatory bacteria and a depletion of anti-inflammatory SCFAs-producing bacteria. Specifically, Actinobacteria, Proteobacteria, Rikenellaceae, Porphyromonadaceae and Bifidobacteriaceae were more abundant in the depression group, as well as Firmicutes, Prevotellacea and Ruminococcaceae in lower abundance. In the anxiety group, the abundance of Firmicutes, Lachnospira, Faecalibacterium, Sutterella, and Butyricicoccus was lower, while the abundance of Bacteroidetes, Enterobacteriaceae, and Fusobacterium was increased.

The systematic review found that depression and anxiety might be characterized by an enrichment of pro-inflammatory bacteria and the depletion of anti-inflammatory SCFAs-producing bacteria. However, there were conflicting reports on the abundance of bacteria due to confounders such as diet and psychotropic medications. Further studies are strongly suggested.

Not applicable.

The dura sinus-resident immune cells can influence the process of central neural system (CNS) diseases by communicating with central nerve cells. In clinical, Tregs are also frequently impaired in depression. However, the significance of this relationship remains unknown. In the present study, we found a significant increase in dural Treg populations in mouse models of depression, whereas depleting them by neutralizing antibodies injection could exacerbate depressive phenotypes. Through RNA sequencing, we identified that the antidepressant effects of dural Tregs are at least in part through the production of amphiregulin, increasing the expression of its receptor EGFR in medial prefrontal cortex (mPFC) pyramidal neurons. Furthermore, dural Tregs expressed high levels of ST2, and their expansion in depressed mice depended on astrocyte-derived IL33 secretion. Our study shows that dural Treg signaling can be enhanced by treatment with fluoxetine, highlighting that dural Tregs can be utilized as a potential target cell in major depressive disorder (MDD).

The study aimed to investigate the association of sleep bruxism (SB) and awake bruxism (AB) with health-related factors.

Data on bruxism and diagnosed diseases, use of psychoactive substances and regular identified psychoactive drugs were collected from 1,962 subjects in the Northern Finland Birth Cohort 1966 through a questionnaire. The associations were analyzed using chi-square tests and binary regression models, adjusting for gender and education, and for anxiety/depression symptoms.

Migraine and gastric/duodenal disorders, use of serotonergic antidepressants and a high number of psychoactive drugs associated significantly with AB and SB. Gastrointestinal diseases associated with SB. Poor general health and hand eczema associated with AB. Based on the multivariate model, depression/anxiety symptoms seemed to mediate the associations of bruxism with depression, hand eczema, self-reported gastric/duodenal disorders and the number of identified drugs.

Several diseases, depression/anxiety symptoms and psychoactive medications were associated with SB and AB, the associations being stronger with AB than SB.

The gut-brain axis (GBA) is a bidirectional communication network between the gastrointestinal tract and the brain, modulated by gut microbiota and related biomarkers. Malnutrition disrupts GBA homeostasis, exacerbating GBA dysfunction through gut dysbiosis, impaired neuroactive metabolite production, and systemic inflammation. Nutraceuticals, including probiotics, prebiotics, synbiotics, postbiotics, and paraprobiotics, offer a promising approach to improving GBA homeostasis by modulating the gut microbiota composition and related neuroactive metabolites. This review aims to elucidate the interplay between gut microbiota-derived biomarkers and GBA dysfunction in malnutrition and evaluate the potential of nutraceuticals in combating malnutrition. Furthermore, it explores the future of personalised nutraceutical interventions tailored to individual genetic and microbiome profiles, providing a targeted approach to optimise health outcomes. The integration of nutraceuticals into GBA health management could transform malnutrition treatment and improve cognitive and metabolic health.

Depressive disorder (a subclass of mental disorders) is characterized by persistent affective symptoms. Without timely therapeutic intervention, it leads to clinical deterioration manifested as reduced quality of life and may increase suicide risk in severe cases. Given its complex etiology, intertwined with intrinsic factors such as genetics and environment, and impacted by various issues such as first-pass effect and blood-brain barrier, the therapeutic efficacy of many antidepressant medications is limited for patients. Therefore, by delving into the exploration of novel antidepressant drugs and biomaterials, this review aims to offer fresh perspectives that may facilitate the discovery of innovative antidepressant medications and enhance their therapeutic outcomes. Notably, the review highlights polymers' crucial role in enhancing antidepressants' pharmacological efficacy and pharmacokinetic properties by optimizing their parameters, and they will undoubtedly become powerful tools in improving antidepressive outcomes in future research.

Alzheimer's disease (AD) has emerged as a global public health priority characterized by escalating prevalence and the limited efficacy of current therapeutic approaches. Although the pathological complexity of AD is well-recognized, its underlying etiology remains incompletely elucidated. Current research highlights a bidirectional gut-brain axis (GBA) interaction, wherein gut microbiome perturbations may impair intestinal barrier stability, influence immune responses, and blood-brain barrier permeability through microbial metabolite-mediated pathways, thereby contributing to AD pathophysiology. Notably, probiotics demonstrate therapeutic potential by restoring gut microbiome homeostasis, reinforcing intestinal barrier integrity, and mitigating neuroinflammatory responses via GBA. This review focuses on investigating the gut microbiome alterations in AD pathogenesis, the interaction of probiotics with GBA, and its significance in AD pathogenesis. By synthesizing current clinical evidence, this review aims to establish a scientific foundation for probiotic-based interventions as a novel therapeutic strategy in AD management.

Gut microbiota has been causally linked with different psychiatric disorders. However, its potential causal association with panic and conduct disorder remains unexplored. Here we used Mendelian randomization to unravel causal association of specific bacterial taxa with these disorders.

We retrieved genomewide association studies' summary-level dataset for gut microbiota (n = 18,340), panic disorder (n = 451,325), and conduct disorder (n = 216,179) from the MiBioGen and FinnGen consortium for two-sample Mendelian randomization (MR) analysis. We used the inverse-variance weighted (IVW) approach to estimate causal effects complemented by other MR methods. Sensitivity analyses were also carried out to assess the validity of our results.

We detected 15 bacterial taxa with suggestive causal associations. The genera Coprobacter (OR = 1.20, 95%CI = 1.04-1.38; P = 0.011; PFDR = 0.37), Senegalimassilia (OR = 1.32, 95%CI = 1.05-1.65; P = 0.015; PFDR = 0.37) and family Rikenellaceae (OR = 1.17, 95%CI = 1.00-1.38; P = 0.046; PFDR = 0.37) increased the risk of panic disorder while genus Coprococcus (OR = 2.39, 95%CI = 1.16-4.92; P = 0.0179; PFDR = 0.97) and class Coriobacteriia (OR = 2.20, 95%CI = 1.01-4.77; P = 0.045; PFDR = 0.36) increased the risk of conduct disorder. The other 10 bacterial taxa function as a protective factor as they potentially reduce the risk of the two psychiatric disorders. There was also the absence of horizontal pleiotropy and heterogeneity.

The result of this study may not be generalizable across non-European ancestral populations.

Our study provides a bedrock for future clinical prevention and treatment of these disorders.

Chronic stress is a widespread problem that significantly affects both physical and mental health, leading to numerous complications such as mood disorders, cognitive impairments, gastrointestinal issues, and chronic diseases. The dysregulation of the hypothalamic pituitary adrenal (HPA) axis and the gut-brain axis underlies several stress related disorders, leading to systemic inflammation, neuroinflammation, dysbiosis, and impaired gut barrier integrity. This review emphasizes the growing significance of probiotics as a potential treatment strategy for addressing chronic stress. Probiotics are living bacteria that provide health benefits when consumed in sufficient quantities, acting via several processes including restoration of gut microbial composition, augmentation of gut barrier integrity, and synthesis bioactive compounds such as neurotransmitters and short-chain fatty acids. These effects lead to reduced systemic and neuroinflammation, enhanced neuroplasticity, and the regulation of stress responsive pathways, including the HPA axis. Moreover, probiotics enhance parasympathetic nervous system activity by modulating vagus signaling. Current review indicates the promise of probiotics in alleviating chronic stress; nonetheless, substantial gaps exist regarding strain specific benefits, appropriate doses, and long-term safety. It is essential to address these constraints by comprehensive, large scale clinical studies and tailored therapies. This review highlights the significance of probiotics as a natural, non-invasive approach to chronic stress management, providing an innovative solution for the worldwide issue of stress related health problems.

As a significant mental health disorder worldwide, the treatment of depression has long faced the challenges of a low treatment rate, significant drug side effects and a high relapse rate. Recent studies have revealed that the gut microbiota and neuronal mitochondrial dysfunction play central roles in the pathogenesis of depression: the gut microbiota influences the course of depression through multiple pathways, including immune regulation, HPA axis modulation and neurotransmitter metabolism. Mitochondrial function serves as a key hub that mediates mood disorders through mechanisms such as defective energy metabolism, impaired neuroplasticity and amplified neuroinflammation. Notably, a bidirectional regulatory network exists between the gut microbiota and mitochondria: the flora metabolite butyrate enhances mitochondrial biosynthesis through activation of the AMPK-PGC1α pathway, whereas reactive oxygen species produced by mitochondria counteract the flora composition by altering the intestinal epithelial microenvironment. In this study, we systematically revealed the potential pathways by which the gut microbiota improves neuronal mitochondrial function by regulating neurotransmitter synthesis, mitochondrial autophagy, and oxidative stress homeostasis and proposed the integration of probiotic supplementation, dietary fiber intervention, and fecal microbial transplantation to remodel the flora-mitochondrial axis, which provides a theoretical basis for the development of novel antidepressant therapies targeting gut-brain interactions.

One of the major issues modern medicine faces is the increasing use of antibiotics in reaction to the increased incidence of infectious agents. The current trend of antibiotic overuse contributes to microbial dysbiosis. Recent studies have hypothesized that antibiotic exposure during pregnancy, which alters the composition of the microbiome, might increase the likelihood of attention deficit hyperactivity disorder (ADHD). In addition to the ongoing discussion about the potential links between antibiotic usage, microbiome dysbiosis, and ADHD, there is a rising interest in integrating AI and ML into healthcare practices. Diagnosis, treatment plans, and prognoses are all enhanced by these technological advancements. Remote monitors or telemedicine monitoring are among the management techniques described in this chapter for effectively managing illnesses. Also discussed are ways to halt the progression of diseases by preventative measures that use biosensor technology and dietary approaches. Personalized treatment programs, disease progression stages, and prognosis evaluations are all made possible with the use of artificial intelligence and machine learning. By using these technologies to provide individualized therapy, healthcare practitioners may get a better understanding of ADHD and perhaps improve patient outcomes.

The gut microbiome has emerged as a novel and intriguing focus in mood disorder research. Emerging evidence demonstrates the significant role of the gut microbiome in influencing mental health, suggesting a bidirectional communication between the gut and the brain. This review examines the latest findings on the gut-microbiota-brain axis and elucidates how alterations in gut microbiota composition can influence this axis, leading to changes in brain function and behavior. Although dietary interventions, prebiotics, probiotics, and fecal microbiota transplantation have yielded encouraging results, significant advances are needed to establish next-generation approaches that precisely target the neurobiological mechanisms of mood disorders. Future research must focus on developing personalized treatments, facilitated by innovative therapies and technological progress, which account for individual variables such as age, sex, drug history, and lifestyle. Highlighting the potential therapeutic implications of targeting the gut microbiota, this review emphasizes the importance of integrating microbiota research into psychiatric studies to develop more effective and personalized treatment strategies for mood disorders.

Over the past two decades, a growing number of studies have been conducted on the role of bidirectional communication through the gut-brain axis in the development of neurodegenerative diseases. These studies were driven by the curious fact that all of these diseases present varying degrees of intestinal involvement included in their wide range of symptoms. A population of cells belonging to the ENS, called enteric glial cells (EGCs), appears to actively participate in this communication between the intestine and the brain, but acting in a dualistic manner, sometimes in reactive gliosis releasing inflammatory mediators, sometimes promoting homeostasis and resilience in the face of inflammatory injuries. To date, the intracellular mechanisms that define the transcriptional profile expressed in EGCs in each situation have not yet been elucidated. This review proposes a discussion on: (1) the complex role of distinct phenotypes of enteric glial cells involved in neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and multiple sclerosis (MS); and (2) innovative strategies such as IDO/TDO inhibitors, Brazil nuts, caffeic acid, polyphenols, among others, that act on EGCs and have the potential to treat neurodegenerative diseases.

Postpartum depressive symptoms (PDS) are a common mental health condition among women after delivery. Although various causative factors have been reported, PDS remains a challenging condition to predict and prevent. The disruption of the gut microbiota due to antibiotic exposure has been reported to affect psychiatric conditions. Similarly, previous research suggests that antibiotic exposure during pregnancy could be related to PDS. Therefore, this prospective study examines the association between antibiotic exposure during pregnancy and PDS for 6 months after delivery. Data were obtained from 65,272 mothers from the Japan environment and children's study, a prospective birth cohort study. The ratios of maternal PDS at 1 and 6 months after delivery were 12.3% and 10.1%, respectively. During pregnancy, 10.7% of women took antibiotics orally. Antibiotic exposure during pregnancy was associated with an increased risk of PDS only at 6 months after delivery (OR = 1.13, 95% CI [1.00, 1.26]), adjusted for potential confounding factors. An increase in Edinburgh Postnatal Depression Scale scores in relation to antibiotic exposure during pregnancy was primarily observed via psychological distress during pregnancy. Although a causal link was not established, antibiotic exposure during pregnancy may be a contributing risk factor for PDS. Therefore, when antibiotic administration is required, clinical practitioners and perinatal care providers should consider the potential risk for PDS.

Gut microbiome is implicated in the onset and progression of major depressive disorder (MDD), but the dynamic alterations of depressive symptoms, gut microbiome, and fecal metabolome across different stages of stress exposure remain unclear. Here, we modified the chronic social defeat stress (CSDS) model to evaluate mice subjected to social defeat stress for 1, 4, 7, and 10 days. Behavioral tests, 16S rRNA, metagenomics, and fecal metabolomics were conducted to investigate the impact of stress exposure on behaviors, gut microbiota and fecal metabolites. We observed that depressive-like behaviors, such as anhedonia and social avoidance, worsened significantly as stress exposure increased. The microbial composition, function, and fecal metabolites exhibited distinct separations across the different social defeat stress groups. Mediation analysis identified key bacteria, such as Lachnospiraceae_UCG-001 and Bacteroidetes, and fecal metabolites like valeric acid and N-acetylaspartate. In our clinical depression cohort, we confirmed that fecal valeric acid levels, were significantly lower in depressive-like mice and MDD patients, correlating closely with stress exposure and anhedonia in mice. Further analysis of serum and brain metabolites in mice revealed sustained changes of N-acetylaspartate abundance in fecal, serum, and cortical samples following increasing stress exposure. Together, this study elucidated the characteristics of depressive-like behaviors, gut microbiome, and fecal metabolome across various social defeat stress exposure, and identified key bacteria and fecal metabolites potentially involved in modulating social defeat stress response and depressive-like behaviors, providing new insights into the pathogenesis and intervention of depression.

Despite the increasing recognition of the interplay between depression and cardiovascular disease (CVD), the precise mechanisms by which depression contributes to the pathogenesis of cardiovascular disease remain inadequately understood. The involvement of gut microbiota and their metabolites to health and disease susceptibility has been gaining increasing attention. In this study, it was found that depression exacerbated cardiac injury, impaired cardiac function (EF%: P < 0.01; FS%: P < 0.05), hindered long-term survival (P < 0.01), and intensified adverse cardiac remodeling (WGA: P < 0.01; MASSON: P < 0.0001) after myocardial ischemia/reperfusion (MI/R) in mice. Then we found that mice receiving microbiota transplants from chronic social defeat stress (CSDS) mice exhibited worse cardiac function (EF%: P < 0.01; FS%: P < 0.01) than those receiving microbiota transplants from non-CSDS mice after MI/R injury. Moreover, impaired tryptophan metabolism due to alterations in gut microbiota composition and structure was observed in the CSDS mice. Mechanistically, we analyzed the metabolomics of fecal and serum samples from CSDS mice and identified indole-3-propionic acid (IPA) as a protective agent for cardiomyocytes against ferroptosis after MI/R via NRF2/System xc-/GPX4 axis, played a role in mediating the detrimental influence of depression on MI/R. Our findings provide new insights into the role of the gut microbiota and IPA in depression and CVD, forming the basis of intervention strategies aimed at mitigating the deterioration of cardiac function following MI/R in patients experiencing depression.

Conflicts between individuals of the same species are common in nature and are mostly resolved with limited aggression. Several theoretical studies, such as the Hawk-Dove (HD) game model, investigate the evolution of limited aggression expressed during conflicts between individuals. These studies mainly focus on the individuals involved in the conflict and their genes. Recently accumulating evidence indicates that microbes are associated with diverse functions of their host and can affect host behavior. Here we extend the classic HD game model to include both the hosts and their microbes, examining how natural selection acts on the microbes. We find that nonaggressive host behavior is more likely to evolve and spread in a population when induced by the microbes residing in the host, compared to nonaggressive behavior induced by host genes. Horizontal transmission allows microbes to colonize new hosts, making their success dependent on the fitness of both the host and its opponent. Therefore, selection on the microbes favors reduced host aggressiveness under wider conditions compared to selection acting on genes alone. Our results suggest that microbes may help explain the ubiquity of nonviolent conflict resolution. Consequently, factors that alter the microbial composition within hosts may affect the aggressiveness level in host populations.

Depression is a debilitating and poorly understood mental disorder. There is an urgency to explore new potential biological mechanisms of depression and the gut microbiota is a promising research area.

Our study was aim to understand regional heterogeneity and potential molecular mechanisms underlying depression induced by dysbiosis of mucus-associated microbiota.

Here, we only selected female macaques because they are more likely to form a natural social hierarchy in a harem-like environment. Because high-ranking macaques rarely displayed depressive-like behaviors, we selected seven monkeys from high-ranking individuals as control group (HC) and the same number of low-ranking ones as depressive-like group (DL), which displayed significant depressive-like behaviors. Then, we collected mucus from the duodenum, jejunum, ileum, cecum and colon of DL and HC monkeys for shotgun metagenomic sequencing, to profile the biogeography of mucus-associated microbiota along duodenum to colon.

Compared with HC, DL macaques displayed noticeable depressive-like behaviors such as longer duration of huddle and sit alone behaviors (negative emotion behaviors), and fewer duration of locomotion, amicable and ingestion activities (positive emotion behaviors). Moreover, the alpha diversity index (Chao) could predict aforementioned depressive-like behaviors along duodenum to colon. Further, we identified that genus Pseudomonas was consistently decreased in DL group throughout the entire intestinal tract except for the jejunum. Specifically, there were 10, 18 and 28 decreased Pseudomonas spp. identified in ileum, cecum and colon, respectively. Moreover, a bacterial module mainly composed of Pseudomonas spp. was positively associated with three positive emotion behaviors. Functionally, Pseudomonaswas mainly involved in microbiota derived lipid metabolisms such as PPAR signaling pathway, cholesterol metabolism, and fat digestion and absorption.

Different regions of intestinal mucus-associated microbiota revealed that depletion of genus Pseudomonas is associated with depressive-like behaviors in female macaques, which might induce depressive phenotypes through regulating lipid metabolism.

Bibliometric analyses are increasingly used to evaluate scientific domains, revealing research trends, productivity, and impact. This study provides a bibliometric analysis of microbiome-related research conducted by Greek scientists. Data were retrieved from the Scopus database, using the keyword "microbiome" (English) for publications until December 2024. Bibliometric analysis was performed using VOSviewer and the bibliometrix package in R. Our findings indicate that research output has increased exponentially since 2018, with the National and Kapodistrian University of Athens and the Aristotle University of Thessaloniki leading microbiome research in Greece. Medicine, biochemistry, genetics, molecular biology, immunology, and microbiology are the predominant research fields. The keyword analysis highlights "microbiome", "microbiota", "probiotics", "prebiotics", "intestinal flora", and "16S rRNA" as central topics. Additionally, we acknowledge the role played by alternative microbial markers, including 18S rRNA/ITS sequencing, for fungal diversity studies. This bibliometric study demonstrates a dynamic and evolving research landscape in Greece and highlights the international relevance of Greek contributions to microbiome science.

Anhedonia, as one of the core symptoms of major depressive disorder (MDD), has been regarded as a potential endophenotype of the disease. Multiple studies have evaluated the potential mechanisms of anhedonia in MDD, and found that MDD patients with anhedonia showed different functions in clinical features. In this review, we focus on the clinical research to explore the differences between MDD patients with and without anhedonia in the clinical manifestations and biological alterations, and elaborate the treatments and prognosis of anhedonia. It is demonstrated that anhedonia is associated with adverse outcomes including more severe depressive episode and suicidality, and poor prognosis in patients with MDD. At the biological level, MDD patients with anhedonia seem to present higher levels of inflammatory factors, abnormal metabolic function and hypermetabolism of BDNF. In brain imaging studies, there are some structural and/ or functional changes in multiple brain regions of subcortical and cortical areas, as well as the limbic system in MDD patients with anhedonia. Meanwhile, preliminary research findings have also indicated that there are associations between intestinal flora imbalance and anhedonia. Moreover, evidence indicated the benefit of some selective serotonin reuptake inhibitors seemed limited on anhedonia, and other treatments including psychotherapy, physical therapy and probiotic interventions has remained to be explored but has interesting potential. Therefore, increased awareness of the anhedonic symptoms and the unique clinical features would benefit improved early diagnosis and therapeutic effects in MDD.

Akkermansia muciniphila (AKK), classified as "lean bacteria," has emerged as a promising candidate for ameliorating metabolic disorders, including obesity, diabetes, and liver disease. In this study, we investigated the therapeutic potential of AKK to counteract metabolic dysfunctions induced by Olanzapine (OLZ), a first-class antipsychotic known for its high therapeutic efficacy but also its association with metabolic disturbances, particularly Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Previous studies have implicated progesterone receptor membrane component 1 (PGRMC1) as a key player in antipsychotic-induced metabolic side effects. Using male C57BL/6J mice fed a high-fat diet, we assessed the effects of AKK supplementation on OLZ-induced metabolic disturbances. Key parameters such as body weight, hepatic injury markers, glucose tolerance, insulin resistance, and lipid metabolism were analyzed. The study revealed that AKK supplementation reduced hepatic lipid accumulation, oxidative stress, and insulin resistance, while normalizing lipid and glucose metabolism. These effects are likely mediated through the restoration of PGRMC1/SIRT1/FOXO1 signaling pathway by AKK. Additionally, changes in gut microbiota composition, including a reduction in pathogenic bacteria such as Lactococcus and enrichment of beneficial bacteria, were observed. Overall, the study suggests that AKK has therapeutic potential to counteract OLZ-induced MASLD by modulating gut microbiota and key metabolic pathways, making it a promising strategy for managing metabolic side effects in patients receiving antipsychotic treatment.

Sleep pattern (sleep duration, trouble sleeping, sleep disorder) is associated with both energy density dietary inflammatory index (EDII) and depression. However, whether depression mediates the EDII-sleep pattern relationship is unclear.

14,305 participants from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2014 were included in this study. Weighted multivariable logistic regression and mediated effect analysis were conducted to analyze the associations between EDII, depression and sleep pattern.

In the regression model with full confounding variables adjusted, the OR (95 % CI) for the association between EDII and sleep pattern was 2.11 (1.44, 3.08). Similarly, comparing the highest to the lowest EDII scores, the association with depression yielded an identical OR of 2.62 (1.89, 3.64). Mediation models showed depressive symptoms mediated 24.06 % of the EDII-sleep pattern link. Analysis by sleep pattern subtypes found depressive symptoms mediated 18.22 % for sleep duration, 30.53 % for sleep disorder (both with substantial direct EDII effects), and 93.73 % for trouble sleeping, where EDII's direct impact was not considerable.

Positive association of EDII with unhealthy sleep pattern is partly mediated by depression, and anti-inflammatory diet could be beneficial.

Major depressive disorder (MDD) is a severe mental disorder with largely unknown mechanisms. Carbonic anhydrases convert CO2 to carbonates and protons, playing roles in various brain functions. Carbonic anhydrase 1 (Car1) is particularly abundant and may be linked to microbiota at interstitial sites. We developed Car1-deficient mice to explore the relationship between depression-like behaviors and gut microbiota. Behavioral tests confirmed depression-like behavior in Car1-/- mice. Fecal samples from Car1-/- and WT mice were collected, and 16S rRNA gene sequencing identified distinct microbiota components between the groups. Car1-/- mice exhibited significantly increased immobility in the tail suspension test (TST) compared to WT mice. The gut microbiota composition differed at the phylum level in p_Bacteroidetes, p_Verrucomicrobia, p_Firmicutes, and p_Tenericutes. At the family level, Car1-/- mice had significantly different abundances in eight microbiota groups compared to WT mice. Car1 deficiency is associated with depressive-like behavior and gut microbiota dysbiosis, potentially linked to depressive-like phenotypes.

Major depressive disorder (MDD) is a leading cause of disability worldwide. While traditional pharmacological treatments are effective for many cases, a significant proportion of patients do not achieve full remission or experience side effects. Nutritional interventions hold promise as an alternative or adjunctive approach, especially for treatment-resistant depression. This review examines the potential role of nutrition in managing MDD through addressing biological deficits and modulating pathways relevant to its pathophysiology. Specifically, it explores the ketogenic diet and gut microbiome modulation through various methods, including probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation. Numerous studies link dietary inadequacies to increased MDD risk and deficiencies in nutrients like omega-3 s, vitamins D and B, magnesium, and zinc. These deficiencies impact neurotransmitters, inflammation, and other biological factors in MDD. The gut-brain axis also regulates mood, stress response, and immunity, and disruptions are implicated in MDD. While medications aid acute symptoms, nutritional strategies may improve long-term outcomes by preventing relapse and promoting sustained remission. This comprehensive review aims to provide insights into nutrition's multifaceted relationship with MDD and its potential for developing more effective integrated treatment approaches.

The primary goal of captive primate management is to ensure optimal health and welfare of the animals in our care. Given that the gut microbiome interacts closely with host metabolism, immunity, and even cognition, it represents a potentially powerful tool for identifying subtle changes in health status across a range of body systems simultaneously. However, thus far, it has not been widely tested or implemented as a monitoring tool. In this study, we used longitudinal microbiome sampling of newly arrived chimpanzees at Chimp Haven to explore the feasibility of using the gut microbiome as a health and welfare biomarker in a sanctuary environment. We also tested the hypothesis that a transition to a new living environment, and integration into new social groupings, would result in temporal changes in chimpanzee gut microbiome composition. The collection of longitudinal microbiome data at Chimp Haven was feasible, and it revealed temporal shifts that were unique to each individual and, in some cases, correlated to other known impacts on health and behavior. We found limited evidence for microbial change over time after arrival at Chimp Haven that was consistent across individuals. In contrast, social group and enclosure, and to a lesser extent, age and sex, were associated with differences in gut microbiome composition. Microbiome composition was also associated with overall health status categories. However, many of the effects we detected were most apparent when using longitudinal data, as opposed to single time point samples. Additionally, we found important effects of technical factors, specifically outdoor temperature and time to collection, on our data. Overall, we demonstrate that the gut microbiome has the potential to be effectively deployed as a tool for health and environmental monitoring in a population of sanctuary chimpanzees, but the design must be carefully considered. We encourage other institutions to apply these approaches and integrate health and physiology data to build on the utility of gut microbiome analysis for ensuring the welfare of captive primates in a range of contexts.

Major depressive disorder (MDD) is a widespread psychiatric condition with substantial socioeconomic impacts, yet single-target pharmacotherapies often yield responses. To address its multifactorial nature, this study employed a multiscale network analysis of herbs, their active components, and MDD-associated protein targets. Using a biased random walk with restart, we calculated interactions between disease-related and herb-derived targets, identifying herbs highly correlated with MDD. Enrichment analysis further revealed key signaling pathways, including oxidative stress, neuroinflammation, and hormone metabolism, underlying these herbs' therapeutic effects. We identified Ephedrae herba, Glehniae radix, Euryales semen, and Campsitis flos as promising candidates, each containing multiple bioactive compounds (such as ephedrine, psoralen, xanthine, and ursolic acid) that modulate critical processes like oxidation-reduction, inflammatory cytokine regulation, and transcriptional control. Network visualization showed how these herbs collectively target both shared and distinct pathways, supporting a synergistic, multi-target therapeutic strategy. This approach underscores the significance of network-based methodologies in addressing complex disorders such as MDD, where focusing on a single target may overlook synergistic interactions. By integrating diverse molecular data, this study provides a systematic framework for identifying novel interventions. Future experimental validation will be crucial to confirm these predictions and facilitate the translation of findings into effective MDD therapies.

Many patients with chronic health conditions experience anxiety, which can have significant implications on physical health outcomes and quality of life. This systematic review and meta-analysis aimed to examine the prevalence of anxiety in gastroenterology and hepatology outpatients, across factors such as physical health condition, type of anxiety, and patient demographics, with the intention to support clinicians in providing effective patient care.

Several recent systematic reviews have been published investigating rates of anxiety in different outpatient settings, and have found consistently high rates across the dermatology, endocrinology, cardiology and respiratory/sleep medicine fields, ranging between 25.1% and 30.3%. Whilst there are established links between gastroenterology and hepatology conditions with anxiety, there has yet to be a study estimating the overall global prevalence of anxiety in this outpatient setting. PubMed, Embase, Cochrane and PsycINFO databases were searched from database inception to January 2023 for studies reporting anxiety in gastroenterology and hepatology outpatients ≥ 16 years of age. Prevalence was extracted from self-report questionnaires, diagnostic interviews, and records. The final meta-analysis included 81 studies, with 28,334 participants. Pooled prevalence of anxiety was 31.2% (95% CI 28.2%-34.4%). Subgroup analyses identified significant differences in prevalence across anxiety type, with health anxiety showing the highest prevalence at 23.7%, followed by generalised anxiety 14.5%, specific phobia 12.5%, panic disorder/agoraphobia 12.2%, social anxiety 11.3%, post-traumatic stress disorder 4.9%, and obsessive-compulsive disorder 4.2%. No other significant differences were found. Anxiety is thus common amongst gastroenterology and hepatology outpatients, and so it is important that careful consideration be given to the identification and management of anxiety in these settings.

The etiology and pathogenesis of trigeminal neuralgia remain unclear. This study examines the connection between gut microbiota and trigeminal neuralgia using Mendelian randomization analysis to provide insights into the disorder's origin and propose potential therapies based on our findings.

We used data from the MiBioGen consortium (13,266 participants) for gut microbiota and the IEU OpenGWAS project (800 cases, 195,047 controls) for trigeminal neuralgia. We checked for heterogeneity and horizontal pleiotropy and used the inverse variance weighting method as our main approach to study the causal link between gut bacteria and trigeminal neuralgia, MR-Egger, simple mode, weighted median, and weighted mode as supplementary methods, with a sensitivity test using leave-one-out analysis. If a bacteria-trigeminal neuralgia link was found, we conducted a reverse analysis for confirmation.

According to the final results, these groups include Butyricimonas (Genus, id = 945, p-value = 0.007, OR = 1.742, 95% CI: 1.165-2.604), unknowngenus (Genus, id = 1000005479, p-value = 0.005, OR = 1.774, 95% CI: 1.187-2.651) and Bacteroidales (Family, p-value = 0.005, OR = 1.774, 95% CI: 1.187-2.651) were causally associated with trigeminal neuralgia. No significant results according to reverse Mendelian randomization analysis.

In our study, we identified specific gut bacteria linked to trigeminal neuralgia. To comprehensively understand their impact and mechanisms, additional randomized trials are necessary.

Candida albicans is a commensal yeast that is a common component of the gastrointestinal (GI) microbiome of humans. C. albicans has been shown to bloom in the GI tract of individuals with alcohol use disorder (AUD) and can promote and increase the severity of alcoholic liver disease (ALD). However, the effects of C. albicans blooms on the host in the context of AUD or AUD-related phenotypes, such as ethanol preference, have been unstudied. In this work, we report a reduction in ethanol consumption and preference in mice colonized with C. albicans. C. albicans-colonized mice exhibited elevated levels of serum PGE2 and reduced ethanol preference was reversed by injection with antagonists of PGE2 receptors. Further, injection of mice with a PGE2 derivative decreased their ethanol preference. These results show that PGE2 acting on its receptors EP1 and EP2 drives reduced ethanol preference in C. albicans-colonized mice. We also showed altered transcription of dopamine receptors in the dorsal striatum of C. albicans-colonized mice and more rapid acquisition of ethanol conditioned taste aversion, suggesting alterations to reinforcement or aversion learning. Finally, C. albicans-colonized mice were more susceptible to ethanol-induced motor coordination impairment showing significant alterations to the behavioral effects of ethanol. This study identifies a member of the fungal microbiome that alters ethanol preference and demonstrates a role for PGE2 signaling in these phenotypes.

This review explores the intricate relationships among the gut microbiota, dietary patterns, and mental health, focusing specifically on depression. It synthesizes insights from microbiological, nutritional, and neuroscientific perspectives to understand how the gut-brain axis influences mood and cognitive function.

Recent studies underscore the central role of gut microbiota in modulating neurological and psychological health via the gut-brain axis. Key findings highlight the importance of dietary components, including probiotics, prebiotics, and psychobiotics, in restoring microbial balance and enhancing mood regulation. Different dietary patterns exhibit a profound impact on gut microbiota composition, suggesting their potential as complementary strategies for mental health support. Furthermore, mechanisms like tryptophan metabolism, the HPA axis, and microbial metabolites such as SCFAs are implicated in linking diet and microbiota to depression. Clinical trials show promising effects of probiotics in alleviating depressive symptoms. This review illuminates the potential of diet-based interventions targeting the gut microbiota to mitigate depression and improve mental health. While the interplay between microbial diversity, diet, and brain function offers promising therapeutic avenues, further clinical research is needed to validate these findings and establish robust, individualized treatment strategies.

It is widely known that the dysregulation of non-coding RNAs (ncRNAs) and dysbiosis of the gut microbiome play significant roles in host development and the progression of various diseases. Emerging evidence has highlighted the bidirectional interplay between ncRNAs and the gut microbiome. This article aims to review the current understanding of the molecular mechanisms underlying the crosstalk between ncRNAs, especially microRNA (miRNA), and the gut microbiome in the context of development and diseases, such as colorectal cancer, inflammatory bowel diseases, neurological disorders, obesity, and cardiovascular disease. Ultimately, this review seeks to provide a foundation for exploring the potential roles of ncRNAs and gut microbiome interactions as biomarkers and therapeutic targets for clinical diagnosis and treatment, such as ncRNA mimics, antisense oligonucleotides, and small-molecule compounds, as well as probiotics, prebiotics, and diets.

The hypothalamus-pituitary-adrenal (HPA) and gut-brain axes are vital biological pathways in depression. The HPA axis regulates the body's stress response, and chronic stress can lead to overactivation of the HPA axis, resulting in elevated cortisol levels that contribute to neuronal damage, particularly in regions such as the hippocampus and prefrontal cortex, both of which are involved in mood regulation and mental disorders. In parallel, the gut-brain axis, a bidirectional communication network between the gut microbiota and the central nervous system, influences emotional and cognitive functions. Imbalances in gut microbiota can affect the HPA axis, promoting inflammation and increasing gut permeability. This allows endotoxins to enter the bloodstream, contributing to neuroinflammation and altering neurotransmitter production, including serotonin. Since the majority of serotonin is produced in the gut, disruptions in this pathway may be linked to depressive symptoms. This review explores the interplay between the HPA axis and the gut-brain axis in the context of depression.

The interplay between human health and the microbiome has gained extensive attention, with probiotics emerging as pivotal therapeutic agents due to their vast potential in treating various health issues. As significant modulators of the gut microbiota, probiotics are crucial in maintaining intestinal homeostasis and enhancing the synthesis of short-chain fatty acids. Despite extensive research over the past decades, there remains an urgent need for a comprehensive and detailed review that encapsulates probiotics' latest insights and applications. This review focusses on the multifaceted roles of probiotics in promoting health and preventing disease, highlighting the complex mechanisms through which these beneficial bacteria influence both gut flora and the human body at large. This paper also explores probiotics' neurological and gastrointestinal applications, focussing on their significant impact on the gut-brain axis and their therapeutic potential in a broad spectrum of pathological conditions. Current innovations in probiotic formulations, mainly focusing on integrating genomics and biotechnological advancements, have also been comprehensively discussed herein. This paper also critically examines the regulatory landscape that governs probiotic use, ensuring safety and efficacy in clinical and dietary settings. By presenting a comprehensive overview of recent studies and emerging trends, this review aims to illuminate probiotics' extensive therapeutic capabilities, leading to future research and clinical applications. However, besides extensive research, further advanced explorations into probiotic interactions and mechanisms will be essential for developing more targeted and effective therapeutic strategies, potentially revolutionizing health care practices for consumers.