The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance, which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation. We leveraged natural behavioral variation in a murine model of voluntary oral morphine self-administration to elucidate the mechanisms by which microbiota influences tolerance. Although all mice shared similar morphine-driven microbiota changes that largely masked informative associations with variability in tolerance, our high-resolution temporal analyses revealed a divergence in the progression of dysbiosis that best explained sustained antinociception. Mice that did not develop tolerance maintained a higher capacity for production of the short-chain fatty acid (SCFA) butyrate known to bolster intestinal barriers and promote neuronal homeostasis. Both fecal microbial transplantation (FMT) from donor mice that did not develop tolerance and dietary butyrate supplementation significantly reduced the development of tolerance independently of suppression of systemic inflammation. These findings could inform immediate therapies to extend the analgesic efficacy of opioids.

The gut microbiome has emerged as a promising target for modulating adverse effects of opioid exposure due to its significant role in health and disease. Opioid use disorder (OUD) has become increasingly prevalent, specifically in women of reproductive age, contributing to an increased incidence of offspring exposed to opioids in utero. Recent studies have shown that prenatal opioid exposure (POE) is associated with notable changes to the maternal gut microbiome, with subsequent implications for the offspring's microbiome and other adverse outcomes. However, the role of the gut microbiome in mediating sex-based differences in pain sensitivity has not yet been investigated. In this study, both male and female C57BL/6 offspring were used to determine sex-based differences in nociception and gut microbial composition as a result of POE. Our data reveals significant sex-based differences in offspring prenatally exposed to opioids. The gut microbiome of opioid-exposed females showed an enrichment of commensal bacteria including Lactobacillus compared to opioid-exposed males. Additionally, POE females demonstrated decreased nociceptive sensitivity, while males demonstrated increased nociceptive sensitivity. RNA sequencing of the prefrontal cortex showed sex-based differences in several canonical pathways, including an increase in the opioid signaling pathway of opioid-exposed females, which was not observed in males. Microbiome modification via maternal probiotic supplementation attenuated sex-based differences throughout the early stages of life. Together, our study provides further insight on sex-based differences arising from POE and highlights the pivotal role of the gut microbiome as a modifiable target for mitigating its negative effects.

Autism spectrum disorder (ASD) is a developmental disorder that is characterized by deficits in social communication and restricted, repetitive, and stereotyped behaviors. In addition to neurobehavioral symptoms, children with ASD often have gastrointestinal symptoms (e.g. constipation, diarrhea, gas, abdominal pain, reflux). Several studies have proposed the role of gut microbiota and metabolic disorders in gastrointestinal symptoms and neurodevelopmental dysfunction in ASD patients; these results offer promising avenues for novel treatments of this disorder. Interventions targeting the gut microbiota - such as fecal microbiota transplant (FMT), microbiota transplant therapy (MTT), probiotics, prebiotics, synbiotics, antibiotics, antifungals, and diet - promise to improve gut health and can potentially improve neurological symptoms. The modulation of the gut microbiota using MTT in ASD has shown beneficial and long-term effects on GI symptoms and core symptoms of autism. Also, the modulation of the gut microbiota to resemble that of typically developing individuals seems to be the most promising intervention. As most of the studies carried out with MTT are open-label studies, more extensive double-blinded randomized control trials are needed to confirm the efficacy of MTT as a therapeutic option for ASD. This review examines the current clinical research evidence for the use of interventions that target the microbiome - such as antibiotics, antifungals, probiotics/prebiotics, synbiotics, and MTT - and their effectiveness in changing the gut microbiota and improving gastrointestinal and neurobehavioral symptoms in ASD.

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.

The human gut microbiome, crucial in various diseases, can be utilized to develop diagnostic models through machine learning (ML). The specific tools and parameters used in model construction such as data preprocessing, batch effect removal and modeling algorithms can impact model performance and generalizability. To establish an generally applicable workflow, we divided the ML process into three above-mentioned steps and optimized each sequentially using 83 gut microbiome cohorts across 20 diseases. We tested a total of 156 tool-parameter-algorithm combinations and benchmarked them according to internal- and external- AUCs. At the data preprocessing step, we identified four data preprocessing methods that performed well for regression-type algorithms and one method that excelled for non-regression-type algorithms. At the batch effect removal step, we identified the "ComBat" function from the sva R package as an effective batch effect removal method and compared the performance of various algorithms. Finally, at the ML algorithm selection step, we found that Ridge and Random Forest ranked the best. Our optimized work flow performed similarly comparing with previous exhaustive methods for disease-specific optimizations, thus is generally applicable and can provide a comprehensive guideline for constructing diagnostic models for a range of diseases, potentially serving as a powerful tool for future medical diagnostics.

Acute stress can enhance or impair synaptic plasticity depending on the nature, duration, and type of stress exposure as well as the brain region examined. The absence of a gut microbiome can also alter hippocampal plasticity. However, the possible interplay between synaptic plasticity, acute stress, and the gut microbiota remains unknown. Here, we examine this interaction and determine whether the gut microbiota impacts stress-induced alterations in hippocampal plasticity. Further, we explored whether exposure to the microbial metabolite butyrate is sufficient to counteract stress-induced alterations in synaptic plasticity. We used electrophysiological and molecular experiments in adult male C57/BL6 antibiotic-treated and acutely stressed mice. In electrophysiological experiments we treated hippocampal slices with 3 μM sodium butyrate to explore the effect of this microbial metabolite. We found the presence of the microbiota essential for the enhancement of both short- and long-term potentiation induced by 15 min of acute restraint stress. Furthermore, butyrate exposure effectively restored the stress-induced enhancement of potentiation in slices from microbiome-depleted animals while also enhancing long-term potentiation independent of stress. In addition, alterations of hippocampal synaptic plasticity markers were noted. Our findings highlight a critical new temporal role for gut-derived metabolites in defining the impact of acute stress on synaptic plasticity.

Antimicrobial resistance (AMR) poses a growing global threat. This review examines AMR from diverse angles, tracing the story of antibiotic resistance from its origins to today's crisis. It explores the rise of AMR, from its historical roots to the urgent need to counter this escalating menace. The review explores antibiotic classes, mechanisms, resistance profiles, and genetics. It details bacterial resistance mechanisms with illustrative examples. Multidrug-resistant bacteria spotlight AMR's resilience. Modern AMR control offers hope through precision medicine, stewardship, combination therapy, surveillance, and international cooperation. Converging traditional and innovative treatments presents an exciting frontier as novel compounds seek to enhance antibiotic efficacy. This review calls for global unity and proactive engagement to address AMR collectively, emphasizing the quest for innovative solutions and responsible antibiotic use. It underscores the interconnectedness of science, responsibility, and action in combatting AMR. Humanity faces a choice between antibiotic efficacy and obsolescence. The call is clear: unite, innovate, and prevail against AMR.

Co-pollution of microplastics (MPs) and novel brominated flame retardants (NBFRs) in aquatic environments is becoming increasingly common in aquatic environments, raising concerns about their comprehensive ecological impacts. This study investigated the effects of fibrous polyethylene terephthalate (PET) MPs on the bioaccumulation and toxicity of decabromodiphenyl ethane (DBDPE) in zebrafish (Danio rerio). In a 28-day water exposure experiment, co-exposure of fibrous MPs and DBDPE significantly increased the bioavailability of DBDPE in zebrafish and prolonged the half-life of DBDPE in vivo. The elimination rates of DBDPE concentration in muscles of single DBDPE exposure and co-exposure groups were 61.58 % and 56.63 %, respectively. Additionally, the co-exposure exacerbated intestinal damage, including structural deterioration and nutrients depletion, disrupted gut microbiota, promoted the enrichment of genes related to reproductive toxicity, and affected the gut-brain axis, indicating complex toxic interactions in zebrafish. Furthermore, genera of Aurantimicrobium, Cypionkella, and Gemmobacter were the gut microbes significantly associated with main differentially expressed genes(DEGs)in the brain. This study emphasized the exacerbating role of fibrous MPs in DBDPE toxicity, providing new insights into the ecological risks posed by the coexistence of MPs and NBFRs in aquatic ecosystems.

BackgroundInsomnia is a common neurological disorder that exhibits connections with the gut microbiota; however, the exact causal relationship remains unclear. MethodsWe conducted a Mendelian randomization (MR) study to systematically evaluate the causal effects of genus-level gut microbiota on insomnia risk in individuals of European ancestry. Summary-level datasets on gut microbiota were sourced from the genome-wide association study (GWAS) of MiBioGen, while datasets on insomnia were obtained from the GWAS of Neale Lab and FinnGen. The primary analytical approach used was the inverse-variance weighted (IVW) method, supplemented by MR-Egger, maximum likelihood, MR-robust adjusted profile score, and weighted median. Sensitivity analyses were conducted to ensure robustness. ResultsThe microbial taxa Enterorhabdus, Family XIII AD3011 group, Paraprevotella, and Lachnospiraceae UCG004 were associated with an increased risk of insomnia, whereas Coprococcus1, Coprobacter, Desulfovibrio, Flavonifractor, Olsenella, Odoribacter, and Oscillibacter were linked to a decreased risk. Regarding the insomnia phenotype characterized by trouble falling asleep, the microbial taxon Eisenbergiella was correlated with an increased risk, while Haemophilus and the Eubacterium brachy group were associated with a reduced risk. Furthermore, for the insomnia phenotype characterized by waking too early, the microbial taxa Family XIII UCG001, Lachnospiraceae FCS020 group, and Olsenella were linked to an increased risk, whereas the Eubacterium brachy group and Victivallis were associated with a lower risk. The results remained robust across all sensitivity analyses. ConclusionOur MR study identified multiple genus-level gut microbial taxa that may exhibit potential causal effects on insomnia from a genetic perspective. These findings provide evidence supporting the theory of the microbiota-gut-brain axis and offer new insights into potential prevention and therapeutic targets for insomnia.

At the time of this writing, most pediatricians or child psychiatrists will probably have treated a child with early acute-onset obsessive compulsive disorder (OCD) behaviors due to the pediatric autoimmune neuropsychiatric disorder associated with Group A beta-hemolytic streptococcus, abbreviated PANDAS, described more than two decades ago; or Tourette syndrome, incorporating motor and vocal tics, described more than a century ago. One typically self-limited post-infectious OCD resulting from exposure to other putative microbial disease triggers defines PANS, abbreviating pediatric autoimmune neuropsychiatric syndrome. Tourette syndrome, PANDAS and PANS share overlapping neuroimaging features of hypometabolism of the medial temporal lobe and hippocampus on brain 18Fluorodeoxyglucose positron emission tomography fused to magnetic resonance imaging (PET/MRI) consistent with involvement of common central nervous system (CNS) pathways for the shared clinical expression of OCD. The field of pediatric neuropsychiatric disorders manifesting OCD behaviors is at a crossroads commensurate with recent advances in the neurobiology of the medial temporal area, with its wide-ranging connectivity and cortical cross-talk, and CNS immune responsiveness through resident microglia. This review advances the field of pediatric neuropsychiatric disorders and in particular PANS, by providing insights through clinical vignettes and descriptive clinical and neuroimaging correlations from the author's file. Neuroscience collaborations with child psychiatry and infectious disease practitioners are needed to design clinical trials with the necessary rigor to provide meaningful insights into the rational clinical management of PANS with the aim of developing evidence-based guidelines for the clinical management of early, abrupt-onset childhood OCD to avert potentially life-long neuropsychological struggles.

Depression is a long-term, related to stress neuropsychiatric disorder, leading to psychological health issues including worthlessness, anhedonia, sleep and appetite disturbances, dysregulated HPA axis, neuronal cell death, and alterations in the gut microbiota (GM). Dysregulated HPA axis increases level of glucocorticoids that induce proinflammatory response with activation of abnormal kynurenine pathway via metabolizing indoleamine-2,3-dioxygenase (IDO). Kynurenine pathway leads to excitotoxicity of N-methyl-D-aspartate (NMDA) receptor responsible for neuronal cell death. Further, probiotics supplementation gained attention from researchers and clinicians to treat neuropsychiatric diseases. GM alteration remains a key reason for depression; however, there is limited information about the role of probiotics on depression involving glucocorticoid receptor and NMDA excitotoxicity through IDO. Chronic unpredictable mild stress (CUMS) model was prepared to check the role of Lactobacillus fermentum ATCC 9338 (LF) and 1-methyl-D-tryptophan (1-MT) in depression. Herein, mice were placed into experimental groups: control, CUMS stressed, CUMS vehicle, CUMS LF, CUMS 1-MT, and CUMS UT (untreated). Results showed that peroral administration of 1 × 108 CFU/day/mouse LF and intraperitoneal dose of 1-MT (15 mg/kg BW/day) alleviate depressive-like behavior and improve motor coordination and walking patterns. Mice supplemented with LF and 1-MT exhibited a decreased expression of GR and NMDAR2b in the cortex, hippocampus, and medulla. Acetylcholinesterase, SOD, and CAT activities were improved in CUMS mice with supplementation of LF and 1-MT. The GM abundance in LF mice was similar to that in control mice. Such study suggests the roles of LF and 1-MT in depression and oxidative stress, and helpful to understand their therapeutic potential through the HPA axis and IDO.

In recent years, the gut microbiota has been increasingly recognized for its influence on various central nervous system diseases mediated by microglia, yet the underlying mechanisms remain unclear. As key metabolites of the gut microbiota, short-chain fatty acids (SCFAs) have emerged as a focal point in understanding microglia-related interactions. In this review, we further refine the connection between the gut microbiota and microglia by introducing the concept of the "SCFAs-microglia" pathway. We summarize current knowledge on this pathway, recent discoveries regarding its role in neurological diseases, and potential pharmacological strategies targeting it. Finally, we outlined the current challenges and limitations in this field of research. We hope this review provides new insights into the role of the gut microbiota in neuroimmune regulation.

Insulin resistance (IR) plays a significant role in the pathophysiology of comorbid type 2 diabetes mellitus (T2DM) and depression (CDD) through multifaceted mechanisms, including dysregulation of insulin signaling (both central and peripheral), neuroendocrine disturbances (hypothalamic-pituitary-adrenal axis dysfunction and monoaminergic neurotransmission impairment), chronic inflammation, oxidative stress, disruption of the microbiota-gut-brain axis, reduced brain-derived neurotrophic factor levels, and altered synaptic plasticity. These IR-related pathways may predispose individuals to depressive symptoms or exacerbate existing mood disorders. A comprehensive understanding of these mechanisms is critical for developing integrated therapeutic strategies that concurrently target metabolic and psychiatric dysfunction. Antidepressant medications exhibit divergent effects on glucose metabolism. Tricyclic antidepressants, particularly amitriptyline and nortriptyline, worsen metabolic profiles by exacerbating IR, promoting weight gain, and inducing hyperglycemia, thereby increasing diabetes risk with prolonged use. Consequently, tricyclic antidepressants should be avoided in metabolically vulnerable populations unless alternatives are unavailable. Mirtazapine presents a paradoxical profile-while its appetite-stimulating effects often lead to weight gain (a known IR risk factor), some evidence suggests potential β-cell function preservation, necessitating cautious use of mirtazapine in individuals with metabolic syndrome. Among selective serotonin reuptake inhibitors, fluoxetine and escitalopram demonstrate favorable metabolic effects, including improved insulin sensitivity and glycemic control, though hypoglycemia risk (particularly with concomitant sulfonylureas) warrants monitoring. Bupropion, a norepinephrine-dopamine reuptake inhibitor, uniquely promotes weight loss and enhances glycemic control, making it a preferred option for depression comorbid with obesity or T2DM. Agomelatine, with its neutral metabolic profile and circadian rhythm-modulating properties, represents a safer alternative for patients with metabolic concerns. Concurrently, certain antidiabetic agents show promise in managing depression. Metformin and sodium-glucose cotransporter-2 inhibitors may be prioritized for diabetic patients at risk for depression, while glucagon-like peptide-1 receptor agonists appear particularly beneficial for obesity-related mood disturbances. Thiazolidinediones offer value in treatment-resistant cases, whereas insulin secretagogues should be used cautiously in psychiatrically vulnerable individuals. Future research should prioritize three key directions: (1) Mechanistic investigations using advanced neuroimaging to elucidate the contribution of IR to depressive phenotypes and evaluate novel interventions (such as intranasal insulin); (2) Precision medicine approaches incorporating biomarkers, including genetic polymorphisms, inflammatory markers, and gut microbiome signatures, to optimize antidepressant selection and develop personalized treatment algorithms; and (3) Therapeutic innovation, including dual GLP-1/GIP agonists and anti-inflammatory-antidepressant combinations, as well as integrating digital health technologies (e.g., continuous glucose monitoring coupled with mood tracking), will enable real-time, data-driven management. These advances will be instrumental in establishing integrated care paradigms for this comorbidity, which intertwines metabolic and psychiatric conditions.

Type I and type II pyrethroids are widely used and frequently detected in agricultural environments. The neurotoxic effects and underlying mechanisms of pyrethroids in native animal populations, including lizards as common farmland inhabitants, remain unclear. This study exposed male lizards (Eremias argus) to type I bifenthrin (BF) and type II fluvalinate (FA) pyrethroids for 28 days, resulting in abnormal behaviors. Targeted analyses indicated that neurotransmitters, including dopamine, GABA, acetylcholine, and choline in lizard plasma, were significantly decreased with alterations in the cholinergic synapse, dopaminergic synapse, and cAMP signaling pathway in the brain after BF and FA treatment. Nervous system-related genes such as CACNA1A, CACNA1B, and CACNA1C were significantly down-regulated and highly correlated with arachidonic acid metabolism pathway-related metabolites in lizard gut. A notable decrease in metabolites within the arachidonic acid metabolism pathway and alterations in the gut microbiome were indicative for anti-inflammatory responses and neurotoxic effects. Interestingly, increased type I BF bioaccumulation in lizard intestines induced a higher abundance of Akkermansia, which resulted in reduced inflammation in the gut and lower neurotoxic effects compared to the low-dose BF exposure group. This study reveals contrasting dose-responses between pyrethroid types and suggests gut-brain axis-regulated neurotoxicity in lizards.

Proton pump inhibitors (PPIs) are widely prescribed, but their link to migraine risk, especially in Asian populations, remains unclear. This longitudinal study aimed to answer the following question: Does PPI exposure show a dose-dependent risk of migraine, varying by subtype and PPI indication in an Asian population?

Using Taiwan's National Health Insurance Research Database (2000-15), we conducted a matched case-control study on PPI exposure. Adults prescribed PPIs for peptic ulcers, gastroesophageal reflux disease, or upper gastrointestinal bleeding were included, excluding those with prior migraines or incomplete data. Controls were matched 1:1 by age, sex, and residence. PPI exposure was measured in cumulative defined daily doses (cDDDs).

The study included 22 834 PPI users (11 417 cases, 11 417 controls) with a mean follow-up of 4.1 ± 3.3 years. The study population comprised 65.6% females and 34.4% males, with no significant sex difference (P = 1.000). Mean age was 47.27 ± 15.16 years in cases and 47.42 ± 15.14 years in controls (P = .444). The average interval from PPI initiation to migraine diagnosis was 2.4 ± 1.9 years. Compared with those with the lowest PPI exposure (cDDD ≤30), migraine risk progressively increases with greater cumulative exposure: cDDD 31-120 [aOR = 1.22, 95% confidence interval (CI) = 1.15-1.30], cDDD 121-365 (aOR = 1.42, 95% CI = 1.32-1.52), and cDDD >365 (aOR = 1.60, 95% CI = 1.41-1.80). This dose-dependent relationship was consistent across migraine subtypes and PPI indications.

This large-scale Asian population study revealed a significant dose-dependent association between PPI exposure and increased migraine risk, emphasizing the need for cautious prescribing and monitoring of migraine symptoms in long-term PPI users, particularly in Asian populations.

The pathogenesis of obesity is complex and incompletely understood, with an underlying interplay between our genetic architecture and obesogenic environment. The public understanding of the development of obesity is shrouded in myths with widespread societal misconceptions. Body Mass Index (BMI) is a highly heritable trait. However, despite reports from recent genome-wide association studies, only a small proportion of the overall heritability of BMI is known to be lurking within the human genome. Other non-genetic heritable traits may contribute to BMI. The gut microbiome is an excellent candidate, implicating complex interlinks with hypothalamic control of appetite and metabolism via entero-endocrine, autonomic, and neuro-humeral pathways. The neonatal gut microbiome derived from the mother via transgenerational transmission (vaginal delivery and breastfeeding) tends to have a permanence within the gut. Conversely, non-maternally derived gut microbiota manifest mutability that responds to changes in lifestyle and diet. We should all strive to optimize our lifestyles and ensure a diet that is replete with varied and unprocessed plant-based foods to establish and nurture a healthy gut microbiome. Women of reproductive age should optimize their gut microbiome, particularly pre-conception, ante- and postnatally to enable the establishment of a healthy neonatal gut microbiome in their offspring. Finally, we should redouble our efforts to educate the populace on the pathogenesis of obesity, and the role of heritable (but modifiable) factors such as the gut microbiome. Such renewed understanding and insights would help to promote the widespread adoption of healthy lifestyles and diets, and facilitate a transition from our current dispassionate and stigmatized societal approach towards people living with obesity towards one that is epitomized by understanding, support, and compassion.

Supplementation with probiotics seems to confer protective effects in individuals with schizophrenia (SZ), although available results are inconclusive. The aim of this study was to systematically review existing randomized clinical trials (RCTs) to critically assess the effect of probiotics on psychiatric symptoms, anthropometric indicators, lipid profiles, glycemic indices, inflammation, and oxidative stress in adults with SZ. A systematic search was conducted in four databases from inception until January 2025. Six RCTs were included in the quantitative analysis that demonstrated beneficial effects of probiotics on SZ severity determined via the Positive and Negative Syndrome Scale (PANSS), with significant reductions in PANSS (MD = -0.50, p = 0.001), PANSS Negative (MD = -0.31, p = 0.050), and PANSS General scores (MD = -0.33, p = 0.036), alongside reductions in body weight (MD = -0.92, p = 0.000), body mass index (MD = -0.53, p = 0.016), and total cholesterol (SMD = -0.34, p = 0.005). Furthermore, probiotic interventions reduced baseline glucose (SMD = -0.59, p = 0.000), insulin (MD = -0.68, p = 0.000), and measures of insulin sensitivity/resistance and significantly improved biomarkers of inflammation and oxidative stress. To summarize, this meta-analysis suggests that probiotics may confer beneficial effects in patients with SZ through improving psychiatric symptoms as well as markers of body weight, lipid and glucose metabolism, inflammation, and oxidative stress.

The research focused on exploring the differences and relationships between gut microbiota and metabolites at various stages of Alzheimer's disease (AD), specifically using APP/PS1 mice at the ages of 6 months and 10 months. To assess metabolites in serum and cortex, and to evaluate gut microbiota profiles in cecal content, UPLC-MS/MS and 16S rRNA sequencing techniques were utilized, respectively. Findings indicated that, in comparison to younger mice, serum concentrations of L-Leucine, thymine, and Glucosamine 6-phosphate were lower, whereas levels of Sorbitol and Palmitic acid were higher. Furthermore, measurements of the ACE and Chao1 indices significantly declined in the older cohort. At the phylum level, the relative abundance of Bacteroidetes showed a decline, while there was an increase in Actinobacteria and TM7 bacteria among the middle-aged subjects. The novelty of this study is we found there were notable alterations in both gut microbiota and metabolites within serum and cortex when comparing young and older APP/PS1 mice, emphasizing the important connections between metabolites and gut microbiota throughout the progression of AD. These results indicate that manipulating metabolites and gut flora may serve as a vital strategy for the prevention and management of AD.

To explore the underlying pharmacological mechanisms and its potential effects of Chinese medicine herbal formula Sini Powder (SNP) on hepatocellular carcinoma (HCC).

The active components of SNP and their in vivo distribution were identified using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Construction of component-target-disease networks, protein-protein interaction network, Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and molecular docking were employed to analyze the active components and anti-HCC mechanisms of SNP. Cell viability assay and wound healing assay were utilized to confirm the effect of SNP-containing serum (2.5%, 5.0%, 10%, 20%, and 40%), isoprenaline or propranolol (both 10, 100, and 1,000 µ mol/L) on proliferation and migration of HepG 2 or Huh7 cells. Meanwhile, the effect of isoprenaline or propranolol on the β 2 adrenergic receptor (ADRB2) mRNA expression on HepG2 cells were measured by real-time quantitative reverse transcription (RT-qPCR). Mice with subcutaneous tumors were either subjected to chronic restraint stress (CRS) followed by SNP administration (364 mg/mL) or directly treated with SNP (364 mg/mL). These two parallel experiments were performed to validate the effects of SNP on stress responses. Stress-related proteins and hormones were quantified using RT-qPCR, enzyme-linked immunosorbent assay, and immunohistochemistry. Metagenomic sequencing was performed to confirm the influence of SNP on the gut microbiota in the tumor-bearing CRS mice.

The distribution of the 12 active components of SNP was confirmed in various tissues and feces. Network pharmacology analysis confirmed the anti-HCC effects of the 5 active components. The potential anti-HCC mechanisms of SNP may involve the epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC) and signal transducer and activator of transcription 3 (STAT3) pathways. SNP-containing serum inhibited the proliferation of HepG2 and Huh7 cells at concentrations of 2.5% and 5.0%, respectively, after 24 h of treatment. Furthermore, SNP suppressed tumor progression in tumor-bearing mice exposed to CRS. SNP treatment also downregulated the expressions of stress-related proteins and pro-inflammatory cytokines, primarily by modulating the gut microbiota. Specifically, the abundance of Alistipes and Prevotella, which belong to the phylum Bacteroidetes, increased in the SNP-treated group, whereas Lachnospira, in the phylum Firmicutes, decreased.

SNP can combat HCC by alleviating stress responses through the regulation of gut microbiota.

This study aimed to apply stress-diathesis model to investigate the prevalence of suicide attempts and associated factors in a nationally representative sample of adolescents.

A cross-sectional design and secondary data analysis were conducted using the parent study "Taiwan Youth Health Survey" data. A total of 5511 junior high school students were included. The outcome variable was self-reported suicide attempts, and the independent variables included self-reported stress and diathesis factors.

The prevalence of suicide attempts among adolescents was 7.7 %, with rates of 6.1 % for boys and 9.4 % for girls. The multiple logistic regression revealed that girls, loneliness, suicide ideation and plans, smoking, drinking alcohol, consumption of carbonated soft drinks (CSDs), eating fast food, experiencing a severe injury, being bullied, and lacking close friends were associated with an increased risk for attempting suicide. For boys, anxiety, smoking, experiencing severe injuries were identified as significant risk factors. For girls, loneliness, drinking alcohol, consuming CSDs, eating fast food, being bullied, and less parental supervision were identified as significant risk factors. The derived prediction score for the total group, boys, and girls yielded areas under the cure of 0.85, 0.82, and 0.87, respectively. The regression model, which incorporated interaction terms, demonstrated that loneliness, consumption of CSDs, and less parental supervision are gender-specific risk factors.

It is essential to consider gender differences in preventive measures. Appropriate interventions should be tailored to address both predispositions and stress unique to each gender, ensuring that gender-specific risk factors are managed more comprehensively.

While existing meta-analysis suggest that probiotic therapies may enhance cognitive functions and influence metabolic characteristics, the findings have been inconclusive. In light of these discrepancies, our study undertakes an umbrella review to more precisely determine the aggregate effects and rigorously evaluate the credibility and quality of evidence.

We conducted a systematic search across seven databases, including PubMed, Embase, the Cochrane Library, ProQuest, Web of Science, CINAHL, and Scopus, from their inception to June 20, 2024. We utilized the AMSTAR-2 tool to evaluate the quality of the meta-analyses and applied the GRADE system to rate the quality of the evidence. We estimated the final effect sizes (ESs) along with their 95% confidence intervals (CI) and performed both sensitivity and subgroup analyses to explore the sources of heterogeneity.

Among the 314 articles identified in our search, 13 meta-analysis that met the criteria were included in the study. The quality of the evidence in these studies was graded from high to very low. Our results demonstrate that probiotic treatment significantly enhances cognitive function in patients (ESSMD = 0.39, 95%CI: 0.19 to 0.59, p < 0.001). Moreover, probiotic treatment notably decreased level of serum malondialdehyde (MDA), insulin resistance as detected by homeostasis model assessment method (HOMA-IR) and high-sensitivity C-reactive protein (hs-CRP) (p < 0.001). Conversely, probiotic treatment did not significantly impact triglycerides and very-low-density lipoprotein (VLDL) in patients (p > 0.05).

Although preliminary evidence indicated that probiotic therapy may positively impact cognitive function, MDA, HOMA-IR, and hs-CRP, the overall quality of the existing evidence is insufficient to provide strong support. Therefore, future research must employ more rigorous designs or initiate larger clinical trials to produce more compelling evidence to further validate the efficacy of probiotic therapy on cognitive function of patients with cognitive dysfunction.

The amygdala, especially its central nucleus (CeA), is one of the key brain structures regulating fear, anxiety and stress responses and is also involved in gut microbiota signal processing. Amygdala hyperactivity, as well as microbiota alterations, plays an important role in the pathophysiology of anxiety disorders, depression or post-traumatic stress disorder (PTSD). The present study determines whether 3 weeks of galactooligosaccharide (GOS) supplementation alleviates behavioural, haematological, immunological and gut microbiota disturbances induced by long-term electrical stimulation of the CeA in rats (Stim). The unsupplemented Stim group showed locomotor hyperactivity and higher anxiety (measured with an actometer and the elevated plus maze, respectively), as well as a decrease in white blood cells (WBCs), lymphocytes (LYMs), red blood cells (RBCs) and platelets (PLTs); an elevation of TNFα; a reduction in IL-10 concentration in plasma; and microbiota alterations as compared to the control (Sham) group. GOS supplementation alleviated all these Stim-induced adverse effects or even normalised them to the sham group level. The effect of GOS was comparable to citalopram and even more effective in WBC and PLT normalisation and IL-10 induction. The obtained results indicate the high therapeutic potential of GOS in anxiety and stress-related disorders. GOS supplementation may support conventional therapy or the prevention of PTSD, depression and anxiety disorders.

Background: The gut-brain axis (GBA) is a complex bidirectional communication system that links the gastrointestinal tract and the central nervous system. Essential oils (EOs) have emerged as promising natural compounds capable of modulating this axis. Methods: A comprehensive analysis of the recent literature was conducted, focusing on studies investigating the effects of EOs on the GBA. Particular attention was given to the endocannabinoid system, the role of cannabis-derived EOs, and other plant-based EOs with potential neuroprotective and gut microbiota-modulating effects. Results: Among the EOs analyzed, cannabis essential oil (CEO) gained attention for its interaction with cannabinoid receptors (CBR1 and CBR2), modulating gut motility, immune responses, and neurotransmission. While acute administration of the CEO reduces inflammation and gut permeability, chronic use has been associated with alterations in gut microbiota composition, potentially impairing cognitive function. Other EOs, such as those from rosemary, lavender, eucalyptus, and oregano, demonstrated effects on neurotransmitter modulation, gut microbiota balance, and neuroinflammation, supporting their potential therapeutic applications in GBA-related disorders. Conclusions: EOs demonstrate promising potential in modulating the GBA through mechanisms including neurotransmitter regulation, gut microbiota modulation, and anti-inflammatory activity. At the same time, phytocannabinoids offer therapeutic value; their long-term use warrants caution due to potential impacts on microbiota. Future research should aim to identify EO-based interventions that can synergistically restore GBA homeostasis and mitigate neurodegenerative and gastrointestinal disorders.

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.

Emerging evidence supports gut microbiota's association with mental distress, particularly depression and anxiety, the microbiota-gut-brain axis was the believed to be the underlying mechanism. This study investigated the causal relationships between specific gut microbiota and depression and anxiety disorders using large-scale genome-wide association study (GWAS) data.

A two-sample bidirectional Mendelian randomization (MR) analysis was conducted to explore the causal effects of 211 microbial taxa on depression and anxiety across three large GWAS databases: FinnGen, Pan-UKBB, and PGC. Sensitive analyses were followed to validate the robustness of results. Random-effect meta-analysis was further performed to enhance the statistical power.

The MR analysis revealed that the Bifidobacteriales (IVW: OR 0.90, 95 %CI 0.83 to 0.98) and Bifidobacteriaceae (IVW: OR 0.90, 95 %CI 0.83 to 0.98) had a protective effect against depression. Clostridiales (cML-MA: OR 0.88, 95 %CI 0.81 to 0.95) and Parasutterella (cML-MA: OR 0.75, 95 %CI 0.64 to 0.88) showed negative associations with depression. Increased abundance of Oxalobacteraceae (cML-MA: OR 1.78, 95 %CI 1.24 to 2.56), Deltaproteobacteria (cML-MA: OR 2.17, 95 %CI 1.38 to 3.40), and Desulfovibrionales (cML-MA: OR 2.22, 95 %CI 1.41 to 3.49) was associated with a higher risk of depression. For anxiety, protective effects were found for Actinobacteria (phylum: IVW: OR 0.83, 95 %CI 0.76 to 0.87; class: IVW: OR 0.84, 95 %CI 0.75 to 0.93), Bifidobacteriales (IVW: OR 0.80, 95 %CI 0.75 to 0.85), Bifidobacteriaceae (IVW: OR 0.80, 95 %CI 0.75 to 0.85) and Bifidobacterium [g] (IVW: OR 0.79, 95 %CI 0.74 to 0.84). Lactobacillaceae [f] (cML-MA: OR 1.18, 95 %CI 1.08 to 1.28), Clostridia [c] (cML-MA: OR 1.15, 95 %CI 0.1.06 to 1.26) and Clostridiales [o] (IVW: OR 1.15, 95 %CI 1.05 to 1.27) were associated with increased anxiety risk. Meta-analysis results indicated significant associations, particularly the protective effects of Actinobacteria (OR 0.90, 95 % CI, 0.83 to 0.98) and Clostridiaceae1 (OR 0.91, 95 % CI, 0.83 to 0.99) on depression and several taxa on anxiety. No significant instrumental variables for depression or anxiety on gut microbiota were identified.

Our findings highlight specific gut microbiota that are associated with depression and anxiety, underscoring the causal relationships between these intestinal microbes and psychiatric disorders. These results suggest potential strategies for mitigating disease symptoms and improving quality of life through microbiome-targeted therapies. Further studies, including randomized controlled trials and investigations into sex-specific effects, are essential to validate and expand upon these findings.

Glyphosate is a broad-spectrum herbicide that inhibits the shikimate pathway, which honey bees (Apis mellifera), a non-target beneficial pollinator, do not endogenously express. Nonetheless, sublethal glyphosate exposure in honey bees has been correlated to impairments in gustation, learning, memory and navigation. While these impacted physiologies underpin honey bee foraging and recruitment, the effects of sublethal glyphosate exposure on these important behaviors remain unclear, and any proximate mechanism of action in the honey bee is poorly understood. We trained cohorts of honey bees from the same hives to forage at one of two artificial feeders offering 1 mol l-1 sucrose solution, either unaltered (N=40) or containing glyphosate at 5 mg acid equivalent (a.e.) l-1 (N=46). We then compared key foraging behaviors and, on a smaller subset of bees, recruitment behaviors. Next, we quantified protein levels of octopamine, tyramine and dopamine, and levels of the amino acid precursor tyrosine in the brains of experimental bees collected 3 days after the exposure. We found that glyphosate treatment bees reduced their foraging by 13.4% (P=0.022), and the brain content of tyramine was modulated by a crossover interaction between glyphosate treatment and the number of feeder visits (P=0.004). Levels of octopamine were significantly correlated with its precursors tyramine (P=0.011) and tyrosine (P=0.018) in glyphosate treatment bees, but not in control bees. Our findings emphasize the critical need to investigate impacts of the world's most-applied herbicide and to elucidate its non-target mechanism of action in insects to create better-informed pollinator protection strategies.

Evidence of changes in the composition and function of the gut microbiota (GM) in post-stroke depression (PSD) patients is gradually accumulating. This study aimed to systematically evaluate the relationship between PSD and GM.

We searched in PubMed, Web of Science, Embase, Cochrane databases, Wangfang, VIP, CBM, and CNKI from the establishment of the database to April 17, 2024, and systematic review and meta-analysis were performed to investigate the differences of GM between patients with PSD spectrum and healthy controls (HC) or stroke spectrum.

There were 14 studies consisting a total of 1,556 individuals included in the meta-analysis. The pooled results showed that PSD spectrum demonstrated significantly increased α diversity as indexed by Chao1 index, ACE indexes, Shannon index, and Simpson index as compared to HC. Additionally, stroke spectrum significantly increased α diversity as indexed by Simpson index compared to PSD. Furthermore, the pooled estimation of relative abundance showed that Bacteroidota, Fusobacteriota, and Pseudomonadota in PSD patients were significantly higher than those in the HC group, while the abundance of Bacillota was higher in the HC group. Moreover, significant differences in GM were observed between PSD patients and HC at the family and genus levels.

This study found that the α diversity of PSD patients was higher than that of HC. Moreover, there were also differences in the distribution of GM at the phylum, family, and genus levels, respectively. At the same time, the level of Lachnospira in PSD patients was lower than that in the stroke group.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024582708.

In this study, we aimed to characterize the gut microbiome and its potential functioning in 2 populations at 2 time points during pregnancy in relation to mental distress.

During the second and third trimester, individuals from the United States and Sweden completed the Edinburgh Postnatal Depression Scale and provided fecal samples for whole-genome metagenomics. A total of 832 and 161 samples were sequenced and analyzed from the Swedish cohort and the U.S. cohort, respectively. Multiple characterizations of the microbial community were analyzed in relation to distress measured using the Edinburgh Postnatal Depression Scale. Principal coordinate analysis and distance-based redundancy analysis assessed variation in functional gut-brain modules. For the U.S. cohort, the Trier Social Stress Test was administered 8 weeks postpartum while collecting salivary cortisol.

Principal coordinate analysis identified 4 sample clusters based on the gut-brain modules distinguished by functions such as short-chain fatty acid synthesis and cortisol degradation. While with distance-based redundancy analysis, mental distress subtypes did not significantly contribute to variation in gut-brain modules (p = .085 for Sweden, p = .23 for the U.S.), a U.S. sample cluster distinguished by lower cortisol degradation from another cluster with higher gut microbial cortisol degradation abundance had significantly higher odds of being associated with depression (p = .024). The U.S. sample cluster with lower gut microbial cortisol degradation abundance also had significantly higher cortisol levels after a postpartum social stressor.

Further studies are warranted to investigate the potential for the gut microbiome to serve as biomarkers of gut-brain axis health during pregnancy across disparate populations.

Microbial communities are not simply remnants of the past but dynamic entities that continuously evolve under the selective pressures of nature, reflecting the intricate and adaptive processes of evolution. The microbiota residing in the various regions of the human body has numerous roles in different physiological processes such as nutrition, metabolism, immune regulation, etc. In the zeal of achieving empirical insights into the ambit of the gut microbiome, the research over the years led to the revelation of reciprocal interaction between the gut microbiome and the cognitive functioning of the human body. Dysbiosis in the gut microbial composition disturbs the homeostatic cognitive functioning of the human body. This dysbiosis has been associated with various chronic diseases, including brain cancer, such as glioma, glioblastoma, etc. This review explores the mechanistic role of dysbiosis-mediated progression of brain cancers and their subtypes. Moreover, it demonstrates the regulatory role of microbial metabolites produced by the gut microbiota, such as short-chain fatty acids, amino acids, lipids, etc., in the tumour progression. Further, we also provide valuable insights into the microbiota mediating the efficiency of therapeutic regimens, thereby leveraging gut microbiota as potential biomarkers and targets for improved treatment outcomes.

Life expectancy and graft survival continue to improve after transplantation. However, improved posttransplant clinical outcomes do not necessarily translate into improved health-related quality of life (HRQoL). Therefore, there is an increased focus on HRQoL in kidney transplant recipients (KTRs). The HRQoL of KTRs is worse than that of the general population, but interventions that improve HRQoL in KTRs are scarce, and health care professionals in nephrology care do not routinely address HRQoL. To improve HRQoL, it is essential to understand which factors play a role in HRQoL and to pinpoint areas for intervention. This narrative review maps the concept of HRQoL within the KTR population and provides a comprehensive overview of factors associated with posttransplant HRQoL. The results are structured using an easy-to-understand conceptual model of HRQoL, which is instrumental for understanding how HRQoL is constituted of many clinical and nonclinical factors. We conclude that symptom burden among KTRs is high, which is likely a key driver of the limited HRQoL in this population. Moreover, myriad other clinical and nonclinical factors are associated with HRQoL, but the majority of the evidence is observational.

Taolimiao-Alashan Nur (T-A Nur) is an important breeding site for the Relict Gulls (Larus relictus) and many other waterbirds. To understand the gut health status of rare bird species living there and to protect these bird species, this study analyzed the gut microbiota of four waterbird species, including Relict Gull (L. relictus), Black-necked Grebe (Podiceps nigricollis), Greylag Goose (Anser anser), and Ruddy Shelduck (Tadorna ferruginea), using 16S rRNA high-throughput sequencing. Results showed that the gut microbiota of Ruddy Shelduck had the highest α-diversity, while Greylag Goose had the lowest. The composition of gut microbiota varied significantly among the bird species. The dominant bacterial phylum in the guts of Black-necked Grebe, Greylag Goose, and Ruddy Shelduck was Firmicutes, while it was Pseudomonadota in Relict Gull. At the genus level, the dominant bacteria were Halomonas in Black-necked Grebe, Escherichia-Shigella in Relict Gull, Ligilactobacillus in Greylag Goose, and Enterococcus in Ruddy Shelduck. Correlation analysis revealed significant relationships among gut bacterial communities, suggesting that gut bacteria can regulate host metabolism and physiological state by their interactions. KEGG functional predictions indicated that gut microbiota were primarily involved in metabolism. The abundance of metabolism-related microorganisms in Relict Gull was significantly lower than in Greylag Goose and Ruddy Shelduck, indicating that the gut microbiota of Greylag Goose and Ruddy Shelduck can provide stronger metabolic functions for the hosts. Additionally, microorganisms related to human diseases were more abundant in the gut of Relict Gull compared to Ruddy Shelduck and Black-necked Grebe, and in Greylag Goose compared to Ruddy Shelduck. These findings suggested that the gut microbiota of birds in this area harbor some human pathogens, which warrants attention and preventive measures.

This study evaluated the antidepressant effects of arecoline, a bioactive alkaloid derived from areca nuts, using a mouse model of depression induced by chronic unpredictable mild stress. Arecoline treatment significantly alleviated depression-like behaviors, including anxiety, anhedonia, and despair, as evidenced by behavioral tests. Mechanistically, arecoline restored serotonin and norepinephrine levels in the brain and serum, reduced pro-inflammatory markers such as IL-1β and LPS in both serum and colon, and enhanced hippocampal neuroplasticity through increased BDNF and PSD-95 expression. Moreover, arecoline modulated gut microbiota composition, particularly enriching beneficial species like Bifidobacterium pseudolongum and Ligilactobacillus murinus, and regulated serum metabolites associated with tryptophan metabolism, neurotransmitter synthesis, and oxidative stress. These findings demonstrate that arecoline exerts its antidepressant effects via a multitargeted approach involving the gut-brain axis, neurotransmitter modulation, and neuroplasticity enhancement. This study highlights arecoline as a promising therapeutic candidate for depression, emphasizing its potential to address both central and peripheral mechanisms.

The human gut microbiome, composed of a vast array of microorganisms that have co-evolved with humans, is crucial for the development and function of brain systems. Research has consistently shown bidirectional communication between the gut and the brain through neuronal, endocrine, and immunological, and chemical pathways. Recent neuroscience studies have linked changes in the microbiome and microbial metabolites to various neuropsychiatric disorders such as autism, depression, anxiety, schizophrenia, eating disorders, and neurocognitive disorders. Novel metagenome-wide association studies have confirmed these microbiome variations in large samples and expanded our understanding of the interactions between human genes and the gut microbiome. The causal relationship between gut microbiota and neuropsychiatric disorders is being elucidated through the establishment of large cohort studies incorporating microbiome data and advanced statistical techniques. Ongoing animal and human studies focused on the microbiota-gut-brain axis are promising for developing new prevention and treatment strategies for neuropsychiatric conditions. The scope of these studies has broadened from microbiome-modulating therapies including prebiotics, probiotics, synbiotics and postbiotics to more extensive approaches such as fecal microbiota transplantation. Recent systematic reviews and meta-analyses have strengthened the evidence base for these innovative treatments. Despite extensive research over the past decade, many intriguing aspects still need to be elucidated regarding the role and therapeutic interventions of the microbiota-gut-brain axis in neuropsychiatric disorders.

Objectives: The aim of this study was to investigate the effects of different stages of training on the intestinal microbial abundance of Yili horses. Methods: Ten Yili horses, all aged 2 years old and weighing 305 ± 20 kg, were selected and divided into a training group and an untrained group. The training group performed riding training 6 days a week, and the untrained group moved freely in the activity circle every day. Fecal samples were collected on days 30 and 60, and the intestinal microorganisms were detected and analyzed using metagenomics. Results: Compared with the 30-day untrained group, the relative abundances of Bacteroidetes were significantly increased in the 30-day training group (p < 0.01). Conversely, the abundances of Clostridiaceae, Clostridium, and Ruminococcus were significantly decreased (p < 0.01), whereas those of Prevotella, Bacteroideaceae, and Bacteroidetes were significantly increased (p < 0.05). Additionally, the relative abundances of Firmicutes and Actinomycetes were significantly decreased (p < 0.05). Compared with the 60-day untrained group, no significant differences in the phyla Bacteriaceae and Bacteriae of the 60-day training group (p > 0.05) were observed. In the linear discriminant analysis effect size analysis, seven significantly different bacteria were detected in the fecal flora of horses in the 30-day training group versus the untrained 30-day group, but only one significantly different bacterium was detected after 60 days. The Kyoto Encyclopedia of Genes and Genomes analysis showed that the differentially expressed genes were related to metabolism and the environmental information processing pathway, carbohydrate metabolism, and membrane transport pathways. Conclusions: Therefore, training seems to affect the diversity and composition of the gut microbiota of Yili horses, especially during the first 30 days of training.

Background: Glutamate, a nutritionally non-essential amino acid, is a key intermediate in nitrogen metabolism. Despite more studies on its functional role in intestine health, it remains unknown how glutamate regulates nitrogen metabolism in animals fed a low-protein diet. Methods: Herein, we investigated the effects of glutamate supplementation on colonic amino acid transport, barrier protein expression, microbiota alterations, fecal nitrogen emissions, hepatic amino acid transport, and protein synthesis in weaned rats. Results: We found that protein restriction diminished the mucus thickness, reduced goblet cell numbers, and the expression of EAAT3, y+LAT2 in the colon. In contrast, glutamate supplementation reversed these effects, increasing the colon length and enhancing the expression of ZO-1, Occludin, and Claudin-1 in the colon. At the genus level, glutamate increased the abundance of Lactococcus and Clostridia_sensu_stricto_18. Additionally, glutamate supplementation resulted in an increased apparent nitrogen digestibility, reduced the ratio of fecal nitrogen to total nitrogen intake, and increased the ratio of fecal microbial nitrogen to total nitrogen intake. Protein restriction decreased the mRNA level of ATP1A1, EAAT3, SNAT9/2, and ASCT2, and the protein level of p-mTOR, mTOR, p-mTOR/mTOR, and p-p70S6K/p70S6K as well as p-4EBP1/4EBP1 in the liver. These effects were reversed by glutamate supplementation. Conclusions: In conclusion, glutamate supplementation upregulates amino acid transporters and barrier protein expression in the colon, modulates microbiota composition to reduce fecal nitrogen excretion, and enhances amino acid transport and protein synthesis in the liver by activating the mTOR/p70S6K/4EBP1 pathway, which influences nitrogen metabolism in weaned rats fed a low-protein diet.

Although evolutionary medicine has produced several novel insights for explaining prevalent health issues, it has yet to sufficiently address possible adverse mental health effects of humans during long-term space missions While evolutionary applications to medicine have increased over the past 20 years, there is scope for the integration of evolutionary applications in the new branch of space medicine called bioastronautics, which analyses the effects on human bodies when in outer space. Evolutionary principles may explain what kinds of space environments increase mental health risks to astronauts, both in the short and long term; secondly, evolutionary principles may provide a more informed understanding of the evolutionary mismatch between terrestrial and space environments in which astronauts exist. This information may assist in developing frameworks for improving mental health of astronauts and future space colonists. Consequently, this paper will focus on some of the major evolutionary mismatches currently confronting astronauts' mental health, with an aim to improve medical knowledge. It will also provide possible therapeutic countermeasures based on evolutionary principles for reducing adverse mental effects on astronauts.

SUMMARYRecent advances in therapeutic probiotics have shown promising results across various health conditions, reflecting a growing understanding of the human microbiome's role in health and disease. However, comprehensive reviews integrating the diverse therapeutic effects of probiotics in human subjects have been limited. By analyzing randomized controlled trials (RCTs) and meta-analyses, this review provides a comprehensive overview of key developments in probiotic interventions targeting gut, liver, skin, vaginal, mental, and oral health. Emerging evidence supports the efficacy of specific probiotic strains and combinations in treating a wide range of disorders, from gastrointestinal (GI) and liver diseases to dermatological conditions, bacterial vaginosis, mental disorders, and oral diseases. We discuss the expanding understanding of microbiome-organ connections underlying probiotic mechanisms of action. While many clinical trials demonstrate significant benefits, we acknowledge areas requiring further large-scale studies to establish definitive efficacy and optimal treatment protocols. The review addresses challenges in standardizing probiotic research methodologies and emphasizes the importance of considering individual variations in microbiome composition and host genetics. Additionally, we explore emerging concepts such as the oral-gut-brain axis and future directions, including high-resolution microbiome profiling, host-microbe interaction studies, organoid models, and artificial intelligence applications in probiotic research. Overall, this review offers a comprehensive update on the current state of therapeutic probiotics across multiple domains of human health, providing insights into future directions and the potential for probiotics to revolutionize preventive and therapeutic medicine.

The aging population worldwide is on the rise, leading to a higher number of Parkinson's disease (PD) cases each year. PD is presently the second most prevalent neurodegenerative disease, affecting an estimated 7-10 million individuals globally. This research aimed to identify mobile genetic elements in human fecal samples using a shotgun metagenomics approach. We identified over 44,000 plasmid contigs and compared plasmid populations between PD patients (n = 68) and controls (n = 68). Significant associations emerged between groups (control vs PD) based on plasmid alpha and beta diversity. Moreover, the gene populations present on plasmids displayed marked differences in alpha and beta diversity between PD patients and controls. We identified a considerable number of phage contigs that were differentially abundant in the two groups. We also developed a predictive machine learning model based on phage abundance data, achieving a mean Area Under the Curve (AUC) of 0.74 with a standard deviation of 0.105 and a mean F1 score of 0.68 with a standard deviation of 0.14 across cross-validation folds, indicating moderate discriminatory power. Additionally, when tested on external data, the model yielded an AUC of 0.74 and an F1 score of 0.8, further demonstrating the predictive potential of phage populations in Parkinson's disease. Further, we improved the continuity and identification of the protein coding regions of the phage contigs by implementing alternative genetic codes.