Previous studies have indicated a potential link between the gut microbiota and obsessive-compulsive disorder (OCD). However, the exact causal relationship remains uncertain. In this study, we employed a two-sample Mendelian randomization (MR) analysis to evaluate the causal connection between gut microbiota and OCD.

We collected Genome-Wide Association Study (GWAS) summary data on gut microbiota (n = 18, 340) and OCD (n = 199, 169), using single nucleotide polymorphisms (SNPs) as the instrumental variable. SNPs with an F-statistic of <10 were deemed weak instrumental variables and subsequently excluded. The MR analysis was conducted using five methods: inverse variance weighting (IVW), MR Egger, weighted median, weighted mode, and simple mode. Heterogeneity and pleiotropy were assessed using Cochran's Q-test and MR Egger intercept test, while sensitivity analysis was performed using a leave-one-out approach.

The IVW analysis revealed that at the phylum level, Proteobacteria (OR = 0.545, 95%CI: 0.347-0.855, P = 0.008) served as a protective factor for OCD, whereas at the order level, Bacillales (OR = 1.327, 95%CI: 1.032-1.707, P = 0.027) was identified as a risk factor. At the family level, Ruminococcaceae (OR = 0.570, 95%CI: 0.354-0.918, P = 0.021) also acted as a protective factor. At the genus level, Bilophila (OR = 0.623, 95%CI: 0.425-0.911, P = 0.015) was a protective factor, while Eubacterium ruminantium group (OR = 1.347, 95%CI: 1.012-1.794, P = 0.041) and Lachnospiraceae UCG001 (OR = 1.384, 95%CI: 1.003-1.910, P = 0.048) were identified risk factors. Reverse MR analysis showed no significant causal relationship between OCD and the gut microbiota, with no significant heterogeneity or horizontal pleiotropy observed.

Our analysis suggested that specific gut microbiota might have a causal relationship with OCD, revealing potential intervention strategies for the prevention and treatment of this disorder.

Numerous studies have shown an interconnection between the gut microbiota and the brain via the "gut-brain" axis. However, the causal relationships between gut microbiota, lipids, and neuropsychiatric disorders remain unclear. This study aimed to analyze potential associations among gut microbiota, lipids, and neuropsychiatric disorders-including AD, PD, ALS, MS, SCZ, MDD, and BD-using summary data from large-scale GWAS.

Bidirectional Mendelian randomization (MR) with inverse variance weighting (IVW) was the primary method. Supplementary analyses included sensitivity analyses, Steiger tests, and Bayesian weighted MR (BWMR). Mediation analyses used two-step MR (TSMR) and multivariable MR (MVMR).

The analyses revealed 51 positive correlations (risk factors) (β > 0, P < 0.05) and 47 negative correlations (protective factors) (β < 0, P < 0.05) between gut microbiota and neuropsychiatric disorders. In addition, 35 positive correlations (β > 0, P < 0.05) and 22 negative correlations (β < 0, P < 0.05) between lipids and neuropsychiatric disorders were observed. Assessment of reverse causality with the seven neuropsychiatric disorders as exposures and the identified gut microbiota and lipids as outcomes revealed no evidence of reverse causality (P > 0.05). Mediation analysis indicated that the effect of the species Bacteroides plebeius on MDD is partially mediated through the regulation of phosphatidylcholine (16:0_20:4) levels (mediation proportion = 10.9 % [95 % CI = 0.0110-0.2073]).

This study provides evidence of a causal relationship between gut microbiota and neuropsychiatric disorders, suggesting lipids as mediators. These findings offer new insights into the mechanisms by which gut microbiota may influence neuropsychiatric disorders.

Alpha-synuclein aggregation, a hallmark of Parkinson's disease (PD), is hypothesized to often begin in the enteric or peripheral nervous system in "body-first" PD and progresses through the vagus nerve to the brain, therefore REM sleep behavior disorder (RBD) precedes the PD diagnosis. In contrast, "brain-first" PD begins in the central nervous system. Evidence that gut microbiome imbalances observed in PD and idiopathic RBD exhibit similar trends supports body-first and brain-first hypothesis and highlights the role of microbiota in PD pathogenesis. However, further investigation is needed to understand distinct microbiome changes in body-first versus brain-first PD over the disease progression.

Our investigation involved 104 patients with PD and 85 of their spouses as healthy controls (HC), with 57 patients (54.8%) categorized as PD-RBD(+) and 47 patients (45.2%) as PD-RBD(-) based on RBD presence before the PD diagnosis. We evaluated the microbiome differences between these groups over the disease progression through taxonomic and functional differential abundance analyses and carbohydrate-active enzyme (CAZyme) profiles based on metagenome-assembled genomes. The PD-RBD(+) gut microbiome showed a relatively stable microbiome composition irrespective of disease stage. In contrast, PD-RBD(-) microbiome exhibited a relatively dynamic microbiome change as the disease progressed. In early-stage PD-RBD(+), Escherichia and Akkermansia, associated with pathogenic biofilm formation and host mucin degradation, respectively, were enriched, which was supported by functional analysis. We discovered that genes of the UDP-GlcNAc synthesis/recycling pathway negatively correlated with biofilm formation; this finding was further validated in a separate cohort. Furthermore, fiber intake-associated taxa were decreased in early-stage PD-RBD(+) and the biased mucin-degrading capacity of CAZyme compared to fiber degradation.

We determined that the gut microbiome dynamics in patients with PD according to the disease progression depend on the presence of premotor RBD. Notably, early-stage PD-RBD(+) demonstrated distinct gut microbial characteristics, potentially contributing to exacerbation of PD pathophysiology. This outcome may contribute to the development of new therapeutic strategies targeting the gut microbiome in PD. Video Abstract.

The intestinal flora (IF) has been linked to risks of non-communicable diseases, especially various cancers, stroke, and Alzheimer's disease. However, many uncertainties of these associations during different stages of growth, development, and aging still exist. Therefore, further in-depth explorations are warranted.

To explore the associations of the human IF with disease risks during different stages of growth, development, and aging to achieve more accurate and convincing conclusions.

Cohort, cross-sectional, case-control, and Mendelian randomization studies published in the PubMed and Web of Science databases until December 31, 2023 were systematically reviewed to clarify the associations of the IF at the genus level with the risks of various non-communicable diseases, which were grouped in accordance with the 10th revision of the International Classification of Diseases.

In total, 57 studies were included to quantitatively examine the influence of the IF on the risks of 30 non-communicable diseases during different stages of growth, development, and aging. Population studies and Mendelian randomization studies confirmed positive associations of the abundances of Bifidobacterium and Ruminococcus with multiple sclerosis.

These findings contribute to a deeper understanding of the roles of the IF and provide novel evidence for effective strategies for the prevention and treatment of non-communicable diseases. In the future, it will be necessary to explore a greater variety of research techniques to uncover the specific mechanisms by which gut microbiota trigger diseases and conduct in-depth studies on the temporal relationship between microbiota alterations and diseases, so as to clarify the causal relationship more accurately.

Primary glomerular diseases (PGDs), including nephrotic syndrome (NS), membranous nephropathy (MN), and IgA nephropathy (IgAN), are complex renal conditions influenced by immune system dysregulation. Although associations between immune cell phenotypes and PGDs have been observed, the precise causal relationships have not been fully elucidated.

Utilizing genetic association data from genome-wide association studies (GWASs), we investigated 731 immunophenotypes in relation to PGDs. A bidirectional two-sample Mendelian randomization (MR) approach, primarily employing inverse variance weighting (IVW), was conducted to establish causality. MR-Egger, weighted median, simple mode, and weighted mode were used as complementary methods to reinforce the robustness and validity of the results. Sensitivity analyses further validated the sensitivity and stability of our results.

We identified 38 immunophenotypes suggestively related to IgAN, with 20 as risk factors and 18 as protective effects. Six immunophenotypes remained significant after Bonferroni correction: The percentage of CD25hi among T cells; the percentage of CD25hi CD45RA- CD4 not T regulatory (Treg) among T cells; the percentage of CD25hi CD45RA- CD4 not Treg within the CD4+ T cell population; CX3CR1 expression on monocytes; CD40 expression on monocytes; and CD64 expression on CD14+ CD16- monocytes. In the validation analysis of IgAN, CD3 expression on effector memory CD4+ T cells further confirmed the predisposing risk role of effector memory T cells in the development of IgAN. Additionally, the MR analysis demonstrated suggestive associations between 25 immunophenotypes and MN (8 risk factors and 17 protective factors), as well as between 22 immunophenotypes and NS (10 risk factors and 12 protective factors). Last, by intersecting the immunophenotypes showing suggestive associations with PGDs, we identified two common immunophenotypes shared by IgAN and MN, three by IgAN and NS, and one by MN and NS.

This genetic-level investigation uncovers causal associations between immunophenotypes and PGDs, providing valuable insights into the immunological underpinnings of PGDs. Our findings suggest potential targets for treatment strategies, thereby facilitating more personalized and effective therapeutic approaches in PGDs management.

Previous studies have suggested a link between gut microbiota and iron-deficiency anemia (IDA). However, interpreting these findings is difficult due to various factors that influence microbiome composition and the limitations of observational studies, such as confounding variables and reverse causation. This study aims to explore the causal relationship between gut microbiota and IDA using Mendelian randomization (MR) to overcome these limitations. We conducted a 2-sample MR analysis using data from genome-wide association studies from the MiBioGen Consortium and the UK Biobank. The gut microbiome data included 211 genus-level microbes linked to single-nucleotide polymorphisms from 18,340 participants in the MiBioGen Consortium. The outcome data for IDA were obtained from 484,598 participants in the UK Biobank, with 2941 cases and 481,657 controls. We assessed causal relationships using various MR techniques, primarily inverse variance weighting, and performed sensitivity analyses to confirm the robustness of our results. Nine genus-level gut microbes were significantly associated with IDA (P < .05). Protective factors included Clostridia, Actinomycetaceae, Pasteurellaceae, Oscillospira, Prevotella, and Roseburia, while risk factors included Ruminococcus gnavus group, Hungatella, and Parasutterella. Sensitivity analyses showed the reliability of these findings without significant variability. This study provides evidence for a causal relationship between specific gut bacteria and IDA risk, identifying potential targets for therapies aimed at improving outcomes for those with IDA. Further research is needed to clarify the bacteria involved.

Observational studies have shown gut microbiota changes in sporadic Creutzfeldt-Jakob disease patients, but the causal relationship remains unknown. We aimed to determine any causal links between gut microbiota and this prion disease. Using Mendelian randomization analysis, we examined the causal relationship between gut microbiota composition and sporadic Creutzfeldt-Jakob disease. Data on gut microbiota (N = 18,340) and disease cases (5208) were obtained. Various analysis methods were used, including inverse variance weighted, Mendelian randomization-Egger, weighted median, simple mode, and weighted mode. In addition, MR-PRESSO was used to evaluate horizontal pleiotropy and detect outliers. Pleiotropy and heterogeneity were assessed, and reverse analysis was conducted. Negative associations were found between sporadic Creutzfeldt-Jakob disease and family Defluviitaleaceae, family Ruminococcaceae, genus Butyricicoccus, genus Desulfovibrio, and genus Eubacterium nodatum. Genus Lachnospiraceae UCG010 showed a positive correlation. Reverse analysis indicated genetic associations between the disease and decreased levels of family Peptococcaceae, genus Faecalibacterium, and genus Phascolarctobacterium, as well as increased levels of genus Butyrivibrio. No pleiotropy, heterogeneity, outliers, or weak instrument bias were observed. This study revealed bidirectional causal effects between specific gut microbiota components and sporadic Creutzfeldt-Jakob disease. Certain components demonstrated inhibitory effects on disease pathogenesis, while others were positively associated with the disease. Modulating gut microbiota may provide new insights into prion disease therapies. Further research is needed to clarify mechanisms and explore treatments for sporadic Creutzfeldt-Jakob disease.

Previous observational studies have hinted at a potential correlation between aplastic anemia (AA) and the gut microbiome. However, the precise nature of this bidirectional causal relationship remains uncertain.

We conducted a bidirectional two-sample Mendelian randomization (MR) study to investigate the potential causal link between the gut microbiome and AA. Statistical analysis of the gut microbiome was based on data from an extensive meta-analysis (genome-wide association study) conducted by the MiBioGen Alliance, involving 18,340 samples. Summary statistical data for AA were obtained from the Integrative Epidemiology Unit database. Single -nucleotide polymorphisms (SNPs) were estimated and summarized using inverse variance weighted (IVW), MR Egger, and weighted median methods in the bidirectional MR analysis. Cochran's Q test, MR Egger intercept test, and sensitivity analysis were employed to assess SNP heterogeneity, horizontal pleiotropy, and stability.

The IVW analysis revealed a significant correlation between AA and 10 bacterial taxa. However, there is currently insufficient evidence to support a causal relationship between AA and the composition of gut microbiome.

This study suggests a causal connection between the prevalence of specific gut microbiome and AA. Further investigation into the interaction between particular bacterial communities and AA could enhance efforts in prevention, monitoring, and treatment of the condition.

Mounting evidence suggests that alterations in gut microbial composition play an active role in the pathogenesis of Parkinson's disease (PD). Probiotics are believed to modulate gut microbiota, potentially influencing PD development through the microbiota-gut-brain axis. However, the potential beneficial effects of Lactiplantibacillus plantarum SG5 (formerly known as Lactobacillus plantarum, abbreviated as L. plantarum) on PD and its underlying mechanisms remain unclear. In this study, we employed immunofluorescence, Western blotting, ELISA, and 16S rRNA gene sequencing to investigate the neuroprotective effects of L. plantarum SG5 against neuroinflammation in an MPTP-induced PD model and to explore the underlying mechanisms. Our results demonstrated that L. plantarum SG5 ameliorated MPTP-induced motor deficits, dopaminergic neuron loss, and elevated α-synuclein protein levels. Furthermore, SG5 inhibited MPTP-triggered overactivation of microglia and astrocytes in the substantia nigra (SN), attenuated disruption of both blood-brain and intestinal barriers, and suppressed the release of inflammatory factors in the colon and SN. Notably, SG5 modulated the composition and structure of the gut microbiota in mice. The MPTP-induced decrease in colonic GLP-1 secretion was reversed by SG5 treatment, accompanied by increased expression of GLP-1R and PGC-1α in the SN. Importantly, the GLP-1R antagonist Exendin 9-39 and PGC-1α inhibitor SR18292 attenuated the protective effects of SG5 in PD mice. In conclusion, we demonstrate a neuroprotective role of L. plantarum SG5 in the MPTP-induced PD mouse model, which likely involves modulation of the gut microbiota and, significantly, the GLP-1/PGC-1α signaling pathway.

The microbiome-gut-brain axis is altered by environmental stressors such as heat, diet, and pollutants as well as microbes in the air, water, and soil. These stressors might alter the host's microbiome and symbiotic relationship by modifying the microbial composition or location. Compartmentalized mutualistic microbes promote the beneficial interactions in the host leading to circulating metabolites and hormones such as insulin and leptin that affect inter-organ functions. Inflammation and oxidative stress induced by environmental stressors may alter the composition, distribution, and activities of the microbes in the microbiomes such that the resultant metabolite and hormone changes are no longer beneficial. The microbiome-gut-brain axis and immune adverse changes that may accompany environmental stressors are reviewed for effects on innate and adaptive immune cells, which may make host immunity less responsive to pathogens and more reactive to self-antigens. Cardiovascular and fluid exchanges to organs might adversely alter organ functionality. Organs, especially the brain, need a consistent supply of nutrients and clearance of debris; disruption of these exchanges by stressors, and involvement of gut microbiome are discussed regarding neural dysfunctions with Alzheimer's disease, autistic spectrum disorders, viral infections, and autoimmune diseases. The focus of this review includes the manner in which environmental stressors may disrupt gut microbiota leading to adverse immune and hormonal influences on development of neuropathology related to hyperhomocysteinemia, inflammation, and oxidative stress, and how certain therapeutics may be beneficial. Strategies are explored to lessen detrimental effects of environmental stressors on central and peripheral health navigated toward (1) understanding neurological disorders and (2) promoting environmental and public health and well-being.

The objective of this review is to provide a comprehensive examination of the role of microbial metabolites in the progression of neurodegenerative diseases, as well as to investigate potential therapeutic interventions targeting the microbiota. A comprehensive literature search was conducted across the following databases: PubMed, Scopus, Web of Science, ScienceDirect, and Wiley. Key terms related to the gut microbiota, microbial metabolites, neurodegenerative diseases, and specific metabolic products were used. The review included both preclinical and clinical research articles published between 2000 and 2024. Short-chain fatty acids have been demonstrated to play a crucial role in modulating neuroinflammation, preserving the integrity of the blood-brain barrier, and influencing neuronal plasticity and protection. Furthermore, amino acids and their derivatives have been demonstrated to exert a significant influence on CNS function. These microbial metabolites impact CNS health by regulating intestinal permeability, modulating immune responses, and directly influencing neuroinflammation and oxidative stress, which are integral to neurodegenerative diseases. Therapeutic strategies, including prebiotics, probiotics, dietary modifications, and fecal microbiota transplantation have confirmed the potential to restore microbial balance and enhance the production of neuroprotective metabolites. Furthermore, novel drug developments based on microbial metabolites present promising therapeutic avenues. The gut microbiota and its metabolites represent a promising field of research with the potential to advance our understanding of and develop treatments for neurodegenerative diseases.

The aim of this study was to reveal the relationship, if any, between gut microbiota and oral ulcers.

We performed a 2-sample Mendelian randomization (MR) study to estimate the roles of gut microbiota in mouth ulcers. The summary datasets of gut microbiota were from the largest genome-wide association study (GWAS) conducted by MiBioGen, and data of mouth ulcers were obtained from UK Biobank. Random effect inverse variance-weighted, weighted median, MR Egger, simple mode and weighted mode were used to estimate the relationship. Sensitivity analyses were conducted to assess the heterogeneity and pleiotropy of instrumental variables. MR Steiger filtering was also applied to orient the causal direction.

Three gut microbiota taxa were positively associated with mouth ulcers: Holdemania (odds ratio [OR] = 1.005, 95% confidence interval [CI]: 1.001-1.009, P = .019), Oxalobacter (OR = 1.004, 95% CI: 1.000-1.007, P = .032), and Ruminococcaceae UCG011 (OR = 1.006, 95% CI: 1.001-1.011, P = .029), while 4 gut microbiota taxa were negatively associated with mouth ulcers: Actinobacteria (OR = 0.992, 95% CI: 0.985-1.000, P = .042), Lactobacillales (OR = 0.995, 95% CI: 0.990-1.000, P = .034), Oscillospira (OR = 0.990, 95% CI: 0.984-0.997, P = .007) and Phascolarctobacterium (OR = 0.992, 95% CI: 0.986-0.997, P = .003). Sensitivity analyses validated the robustness of the association in between.

This MR study identified a strong association between the quality of gut microbiota and oral ulcers. The findings are likely to expand the therapeutic targets for mouth ulcers.

Previous studies have shown a bidirectional communication between human gut microbiota and the brain, known as the microbiota-gut-brain axis (MGBA). The MGBA influences the host's nervous system development, emotional regulation, and cognitive function through neurotransmitters, immune modulation, and metabolic pathways. Factors like diet, lifestyle, genetics, and environment shape the gut microbiota composition together. Most research have explored how gut microbiota regulates host physiology and its potential in preventing and treating neurological disorders. However, the individual heterogeneity of gut microbiota, strains playing a dominant role in neurological diseases, and the interactions of these microbial metabolites with the central/peripheral nervous systems still need exploration. This review summarizes the potential role of gut microbiota in driving neurodevelopmental disorders (autism spectrum disorder and attention deficit/hyperactivity disorder), neurodegenerative diseases (Alzheimer's and Parkinson's disease), and mood disorders (anxiety and depression) in recent years and discusses the current clinical and preclinical gut microbe-based interventions, including dietary intervention, probiotics, prebiotics, and fecal microbiota transplantation. It also puts forward the current insufficient research on gut microbiota in neurological disorders and provides a framework for further research on neurological disorders.

Airway allergic disease (AAD) is a class of autoimmune diseases with predominantly Th2-type inflammation, mainly including allergic rhinitis (AR), allergic asthma (AS), and chronic sinusitis (CRS). There are very complex regulatory mechanisms between immune cells and AAD; however, previous reports found that the functions of the same immune cells in AAD are not identical.

The aim of this study was to explore the causal relationship between different phenotypic immune cells and their association with AAD.

Utilizing the publicly available Genome-Wide Association Studies (GWAS) database, this study conducted a bidirectional Mendelian randomization (MR) to assess the causal relationship between immune cells of 731 different immunophenotypes and AAD. The primary assessment methods included inverse variance weighting, weighted median, and MR Egger. Additionally, sensitivity analyses such as MR-PRESSO, leave-one-out, and scatter plots were employed to eliminate the interference of heterogeneity and pleiotropy, ensuring the stability of the causal inference.

A total of 38 immune cells with different immunophenotypes were found to be positively and causally associated with AR, of which 26 were protective factors and 12 were risk factors. Positive associations were found between 33 immune cells and AS, of which 14 were protective factors and 19 were risk factors, as well as between 39 immune cells and CRS, of which 22 were protective factors and 17 were risk factors. Finally, the results of all relevant immune cells for the three diseases were taken and intersected, and it was found that CD3 on CD39+-activated Treg (IVWAR = 0.001, IVWCRS = 0.043, IVWAS = 0.027) may be the key immune cell that inhibits the development of AAD (ORAR = 0.940, ORAS = 0.967, ORCRS = 0.976).

This study reveals that different immune phenotypes of immune cells are closely related to AAD at the genetic level, which provides a theoretical basis for future clinical studies.

Previous studies have suggested a potential association between gut microbiota and neurological and psychiatric disorders. However, the causal relationship between gut microbiota and cognitive performance remains uncertain.

A two-sample Mendelian randomization (MR) study used SNPs linked to gut microbiota (n = 18,340) and cognitive performance (n = 257,841) from recent GWAS data. Inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode were employed. Heterogeneity was assessed via Cochran's Q test for IVW. Results were shown with funnel plots. Outliers were detected through leave-one-out method. MR-PRESSO and MR-Egger intercept tests were conducted to address horizontal pleiotropy influence.

Limited to European populations, generic level, and potential confounding factors.

IVW analysis revealed detrimental effects on cognitive perfmance associated with the presence of genus Blautia (P = 0.013, 0.966[0.940-0.993]), Catenibacterium (P = 0.035, 0.977[0.956-0.998]), Oxalobacter (P = 0.043, 0.979[0.960-0.999]). Roseburia (P < 0.001, 0.935[0.906-0.965]), in particular, remained strongly negatively associated with cognitive performance after Bonferroni correction. Conversely, families including Bacteroidaceae (P = 0.043, 1.040[1.001-1.081]), Rikenellaceae (P = 0.047, 1.026[1.000-1.053]), along with genera including Paraprevotella (P = 0.044, 1.020[1.001-1.039]), Ruminococcus torques group (P = 0.016, 1.062[1.011-1.115]), Bacteroides (P = 0.043, 1.040[1.001-1.081]), Dialister (P = 0.027, 1.039[1.004-1.074]), Paraprevotella (P = 0.044, 1.020[1.001-1.039]) and Ruminococcaceae UCG003 (P = 0.007, 1.040[1.011-1.070]) had a protective effect on cognitive performance.

Our results suggest that interventions targeting specific gut microbiota may offer a promising avenue for improving cognitive function in diseased populations. The practical application of these findings has the potential to enhance cognitive performance, thereby improving overall quality of life.

Hemorrhoidal disease (HEM) is a common condition affecting a significant proportion of the population. However, the causal relationship between the gut microbiota and hemorrhoids remains unclear. In this study, we employed a Mendelian randomization (MR) approach to investigate the potential associations between them. In this study, the exposure factor was determined by selecting summary statistics data from a large-scale gut microbiome whole-genome association study conducted by the MiBioGen Consortium, which involved a sample size of 18,340 individuals. The disease outcome data consisted of 218,920 cases of HEM and 725,213 controls of European ancestry obtained from the European Bioinformatics Institute dataset. Two-sample MR analyses were performed to assess the causalities between gut microbiota and hemorrhoids using various methods, including inverse-variance weighting, MR-Egger regression, MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), simple mode, and weighted median. Reverse MR analyses were performed to examine reverse causal association. Our findings suggest phylum Cyanobacteria (OR = 0.947, 95% CI: 0.915-0.980, P = 2.10 × 10 - 3), genus Phascolarctobacterium (OR = 0.960, 95% CI: 0.924-0.997, P = .034) and family FamilyXI (OR = 0.974, 95% CI: 0.952-0.997, P = .027) have potentially protective causal effects on the risk of HEM, while genus Ruminococcaceae_UCG_002 (OR = 1.036, 95% CI: 1.001-1.071, P = .042), family Peptostreptococcaceae (OR = 1.042, 95% CI: 1.004-1.082, P = .029), genus Oscillospira (OR = 1.048, 95% CI: 1.005-1.091, P = .026), family Alcaligenaceae (OR = 1.048, 95% CI: 1.005-1.091, P = .036) and order Burkholderiales (OR = 1.074, 95% CI: 1.020-1.130, P = 6.50 × 10-3) have opposite effect. However, there was a reverse causal relationship between HEM and genus Oscillospira (OR = 1.140, 95% CI: 1.002-1.295, P = .046) This is the first MR study to explore the causalities between specific gut microbiota taxa and hemorrhoidal disease, which may offer valuable insights for future clinical interventions for hemorrhoidal disease.

Like other infections, a SARS-CoV-2 infection can also trigger Post-Acute Infection Syndromes (PAIS), which often progress into myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS, characterized by post-exercise malaise (PEM), is a severe multisystemic disease for which specific diagnostic markers or therapeutic concepts have not been established. Despite numerous indications of post-infectious neurological, immunological, endocrinal, and metabolic deviations, the exact causes and pathophysiology remain unclear. To date, there is a paucity of data, that changes in the composition and function of the gastrointestinal microbiota have emerged as a potential influencing variable associated with immunological and inflammatory pathways, shifts in ME/CFS. It is postulated that this dysbiosis may lead to intestinal barrier dysfunction, translocation of microbial components with increased oxidative stress, and the development or progression of ME/CFS. In this review, we detailed discuss the findings regarding alterations in the gastrointestinal microbiota and its microbial mediators in ME/CFS. When viewed critically, there is currently no evidence indicating causality between changes in the microbiota and the development of ME/CFS. Most studies describe associations within poorly defined patient populations, often combining various clinical presentations, such as irritable bowel syndrome and fatigue associated with ME/CFS. Nevertheless, drawing on analogies with other gastrointestinal diseases, there is potential to develop strategies aimed at modulating the gut microbiota and/or its metabolites as potential treatments for ME/CFS and other PAIS. These strategies should be further investigated in clinical trials.

Parkinson's disease (PD) is a common, chronic, and progressive degenerative disease of the central nervous system for which there is no effective treatment. Gastrodia elata is a well-known food and medicine homologous resource with neuroprotective potential. Gastrodia elata polysaccharide (GEP), which is a highly active and safe component in Gastrodia elata, is an important ingredient in the development of functional products. In this study, GEP was administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice over 3 weeks to investigate its neuroprotective effects. The results showed that GEP significantly alleviated the motor dysfunction of PD mice, inhibited the accumulation of α-synuclein, and reduced the loss of dopaminergic neurons in the brain. Moreover, GEP increased the Bcl-2/Bax ratio and decreased the cleaved-caspase-3 level, suggesting that GEP may ameliorate PD by preventing MPTP-induced mitochondrial apoptosis. GEP also significantly inhibited the increase of GFAP and decreased the levels of TNF-α, IL-1β, and IL-6 in the brain of PD mice, which may be the result of the inhibition of neuroinflammation by the inactivation of the TLR4/NF-κB pathway. Furthermore, the neuroprotective effects of GEP involve the gut-brain axis, as it has been shown that GEP regulated the dysbiosis of PD-related gut microbiota such as Akkermansia, Lactobacillus, Bacteroides, Prevotella, and Faecalibacterium, increased the content of microbial metabolites SCFAs in the colon and increased the level of occludin that repairs the intestinal barrier of PD mice. In conclusion, this study is expected to provide a theoretical basis for the development and application of functional products with GEP from the perspective of neuroprotective effects.

Many clinical studies have demonstrated a correlation between psoriasis vulgaris and dementia, yet this correlation remains controversial. Our study employed the Mendelian randomization (MR) method to investigate the causal relationship between psoriasis vulgaris and dementia. Data were obtained from the summary statistics of the genome-wide association studies from IEU-OpenGWAS project database. In univariate Mendelian randomization (UVMR) analysis, psoriasis vulgaris was used as exposure. Alzheimer disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD) and frontotemporal dementia (FTD) served as the outcomes. In multivariate Mendelian randomization (MVMR) analysis, VaD served as the outcome. The first MVMR analysis used psoriasis vulgaris, mean platelet volume (MPV), platelet distribution width (PDW) and platelet count (PLT) as exposures. The second MVMR analysis used psoriasis vulgaris, vitamin D level and 25 hydroxyvitamin D level as exposures. The main analysis employed the inverse variance weighted method, and the outcomes were evaluated by odds ratio (OR) and 95% confidence interval (95% CI). In UVMR analysis, the results depicted that psoriasis vulgaris was associated with VaD (OR: 0.903, 95% CI: 0.818-0.996, p = 0.041). The results revealed insignificant associations between psoriasis vulgaris and other dementia types. After adjusting the effects of MPV, PDW and PLT in MVMR analysis, the association between psoriasis vulgaris and VaD was no longer significant (p = 0.164). Similarly, after adjusting the effects of vitamin D level and 25 hydroxyvitamin D level in MVMR analysis, the association between psoriasis vulgaris and VaD was also no longer significant (p = 0.533). Our study suggests that psoriasis vulgaris may potentially decrease VaD incidence. However, the causal association between psoriasis vulgaris and VaD may be impeded by platelet-related indices, vitamin D level and 25 hydroxyvitamin D level.

Myasthenia gravis (MG) is an autoimmune disease observed to have connections with gut microbiome. We aimed to systematically assess the causal relationships between gut microbiome, gut microbiome-derived metabolites, and MG using Mendelian randomization (MR) approach.

Summary-level genetic datasets from large-scale genome-wide association studies regarding 196 gut microbial taxa from the MiBioGen consortium (n=18,340), 72 derived metabolites from the TwinsUK and KORA studies (n=7,824), and antiacetylcholine receptor (AChR) antibody-positive MG (case=1,873, control=36,370) were employed for MR causal estimates. The inverse-variance weighted (IVW) method was utilized as the main analysis with MR-Egger, maximum likelihood, simple mode, and weighted median as complements. The tests of Cochran's Q, MR-Egger intercept, Steiger, MR-PRESSO and leave-one-out were implemented for sensitivity analyses.

The forward MR estimates of IVW revealed significant causal associations of the abundance of phylum Actinobacteria, class Gammaproteobacteria, family Defluviitaleac, family Family XIII, and family Peptococcaceae with a reduced risk of MG. Conversely, the abundance of phylum Lentisphaerae, order Mollicutes RF9, order Victivallales, and genus Faecalibacterium was causally associated with an increased risk of MG. The reversed MR analysis proved negative causal correlations between the MG and the abundance of family Peptostreptococcaceae, genus Romboutsia, and genus Subdoligranulum. Regarding the derived metabolites, the IVW estimates revealed that elevated levels of beta-hydroxyisovalerate and methionine were causally associated with a decreased risk of MG, while increased levels of choline and kynurenine were linked to an increased risk of MG. Furthermore, genetically predicted MG was associated with a decreased level of cholesterol. The results obtained from complementary MR methods were similar. These findings remained robust in all sensitivity analyses.

Our MR findings support the causal effects of specific gut microbiome taxa and derived metabolites on AChR antibody-positive MG, and vice versa, yielding novel insights into prevention and therapy targets of MG. Future studies may be warranted for validation and pursuing the precise mechanisms.

Previous observational studies have indicated that an imbalance in gut microbiota may contribute to non-alcoholic fatty liver disease (NAFLD). However, given the inevitable bias and unmeasured confounders in observational studies, the causal relationship between gut microbiota and NAFLD cannot be deduced. Therefore, we employed a two-sample Mendelian randomization (TSMR) study to assess the causality between gut microbiota and NAFLD.

The gut microbiota-related genome-wide association study (GWAS) data of 18,340 individuals were collected from the International MiBioGen consortium. The GWAS summary data for NAFLD from the Anstee cohort (1,483 cases and 17,781 controls) and the FinnGen consortium (894 cases and 217,898 controls) were utilized in the discovery and verification phases, respectively. The inverse variance weighted (IVW) method was used as the principal method in our Mendelian randomization (MR) study, with sensitivity analyses using the MR-Egger, weighted median, simple mode, and weighted mode methods. The MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were conducted to identify heterogeneity and pleiotropy. Moreover, a fixed-effect meta-analysis was conducted to verify the robustness of the results.

The gene prediction results showed that at the genus level, four gut microbiota were causally associated with NAFLD in the GWAS conducted by Anstee et al. The relative abundance of Intestinimonas (OR: 0.694, 95%CI: 0.533-0.903, p = 0.006, IVW), Lachnoclostridium (OR: 0.420, 95%CI: 0.245-0.719, p = 0.002, IVW), and Senegalimassilia (OR: 0.596, 95%CI: 0.363-0.978, p = 0.041, IVW) was negatively associated with NAFLD. The relative abundance of Ruminococcus1 (OR: 1.852, 95%CI: 1.179-2.908, p = 0.007, IVW) was positively correlated with NAFLD. Among them, the Lachnoclostridium genus was validated in FinnGen GWAS (OR: 0.53, 95%CI: 0.304-0.928, p = 0.026, IVW). The Lachnoclostridium genus was also significantly associated with NAFLD risk in the meta-analyses (OR: 0.470, 95%CI: 0.319-0.692, p = 0.0001, IVW). No heterogeneity or pleiotropy was observed.

This study provided new evidence of the relationship between the Lachnoclostridium genus and NAFLD, suggesting that augmentation of the relative abundance of the Lachnoclostridium genus through the oral administration of probiotics or fecal microbiota transplantation could be an effective way to reduce the risk of NAFLD.

Observational studies have demonstrated an association between gut microbiota and myasthenia gravis; however, the causal relationship between the two still lacks clarity. Our goals are to ascertain the existence of a bidirectional causal relationship between gut microbiota composition and myasthenia gravis, and to investigate how gut microbiota plays a role in reducing the risk of myasthenia gravis.

We acquired gut microbiota data at the phylum, class, order, family, and genus levels from the MiBioGen consortium (N = 18,340) and myasthenia gravis data from the FinnGen Research Project (426 cases and 373,848 controls). In the two-sample Mendelian randomization analysis, we assessed the causal relationship between the gut microbiota and myasthenia gravis. We also conducted bidirectional MR analysis to determine the direction of causality. The inverse variance weighted, mendelian randomization-Egger, weighted median, simple mode, and weighted mode were used to test the causal relationship between the gut microbiota and severe myasthenia gravis. We used MR-Egger intercept and Cochran's Q test to assess for pleiotropy and heterogeneity, respectively. Furthermore, we utilized the MR-PRESSO method to evaluate horizontal pleiotropy and detect outliers.

In the forward analysis, the inverse-variance weighted method revealed that there is a positive correlation between the genus Lachnoclostridium (OR = 2.431,95%CI 1.047-5.647, p = 0.039) and the risk of myasthenia gravis. Additionally, the family Clostridiaceae1 (OR = 0.424,95%CI 0.202-0.889, p = 0.023), family Defluviitaleaceae (OR = 0.537,95%CI  0.290-0.995, p = 0.048), family Enterobacteriaceae (OR = 0.341,95%CI  0.135-0.865, p = 0.023), and an unknown genus (OR = 0.407,95%CI  0.209-0.793, p = 0.008) all demonstrated negative correlation with the risk of developing myasthenia gravis. Futhermore, reversed Mendelian randomization analysis proved a negative correlation between the risk of myasthenia gravis and genus Barnesiella (OR = 0.945,95%CI  0.906-0.985, p = 0.008).

Our research yielded evidence of a causality connection in both directions between gut microbiota and myasthenia gravis. We identified specific types of microbes associated with myasthenia gravis, which offers a fresh window into the pathogenesis of this disease and the possibility of developing treatment strategies. Nonetheless, more studies, both basic and clinical, are necessary to elucidate the precise role and therapeutic potential of the gut microbiota in the pathogenesis of myasthenia gravis.

Studies have shown a close relationship between gut microbiota (GM) and Alzheimer's disease (AD). However, the causal relationship between them remains unclear.

We conducted a genome-wide association study (GWAS) using publicly available summary statistics data for GM and AD. We extracted independent genetic loci significantly associated with GM relative abundances as instrumental variables based on predefined thresholds (p < 1*e-5). The inverse variance-weighted (IVW) method was primarily used for causal relationship assessment. Additional analyses, including MR-Egger, weighted median, simple mode, and weighted mode, were performed as supplementary analyses.

IVW analysis revealed significant correlations between certain microbial taxa and the risk of AD. Higher abundances of Actinobacteria at the class level, phylum. Actinobacteria, class. Deltaproteobacteria, order. Desulfovibrionales, genus. Oscillospira, and genus. Ruminococcaceae UCG004 (p < 0.048) was found to be positively associated with an elevated risk of AD. However, within the genus-level taxa, Ruminococcus1 (p = 0.030) demonstrated a protective effect on lowering the risk of AD. In addition, to ensure the robustness of the findings, we employed Cochrane's Q test and leave-one-out analysis for quality assessment, while the stability and reliability of the results were validated through MR-Egger intercept test, MR-PRESSO global test, and sensitivity analysis.

This study provided a comprehensive analysis of the causal relationship between 211 GM taxa and AD. It discerned distinct GM taxa linked to the susceptibility of AD, thereby providing novel perspectives on the genetic mechanisms governing AD via the GM. Additionally, these discoveries held promise as valuable biomarkers, enabling the identification of potential therapeutic targets and guiding forthcoming AD investigations.

The composition, viability and metabolic functionality of intestinal microbiota play an important role in human health and disease. Studies on intestinal microbiota are often based on fecal samples, because these can be sampled in a non-invasive way, although procedures for sampling, processing and storage vary. This review presents factors to consider when developing an automated protocol for sampling, processing and storing fecal samples: donor inclusion criteria, urine-feces separation in smart toilets, homogenization, aliquoting, usage or type of buffer to dissolve and store fecal material, temperature and time for processing and storage and quality control. The lack of standardization and low-throughput of state-of-the-art fecal collection procedures promote a more automated protocol. Based on this review, an automated protocol is proposed. Fecal samples should be collected and immediately processed under anaerobic conditions at either room temperature (RT) for a maximum of 4 h or at 4 °C for no more than 24 h. Upon homogenization, preferably in the absence of added solvent to allow addition of a buffer of choice at a later stage, aliquots obtained should be stored at either -20 °C for up to a few months or -80 °C for a longer period-up to 2 years. Protocols for quality control should characterize microbial composition and viability as well as metabolic functionality.

The causal association between the gut microbiome and the development of migraine and its subtypes remains unclear.

The single nucleotide polymorphisms concerning gut microbiome were retrieved from the gene-wide association study (GWAS) of the MiBioGen consortium. The summary statistics datasets of migraine, migraine with aura (MA), and migraine without aura (MO) were obtained from the GWAS meta-analysis of the International Headache Genetics Consortium (IHGC) and FinnGen consortium. Inverse variance weighting (IVW) was used as the primary method, complemented by sensitivity analyses for pleiotropy and increasing robustness.

In IHGC datasets, ten, five, and nine bacterial taxa were found to have a causal association with migraine, MA, and MO, respectively, (IVW, all P < 0.05). Genus.Coprococcus3 and genus.Anaerotruncus were validated in FinnGen datasets. Nine, twelve, and seven bacterial entities were identified for migraine, MA, and MO, respectively. The causal association still exists in family.Bifidobacteriaceae and order.Bifidobacteriales for migraine and MO after FDR correction. The heterogeneity and pleiotropy analyses confirmed the robustness of IVW results.

Our study demonstrates that gut microbiomes may exert causal effects on migraine, MA, and MO. We provide novel evidence for the dysfunction of the gut-brain axis on migraine. Future study is required to verify the relationship between gut microbiome and the risk of migraine and its subtypes and illustrate the underlying mechanism between them.

Background: The microbiota-gut-brain axis has been proposed as a potential therapeutic target of PD. The effects of curcumin against Parkinson's disease have been demonstrated; however, its neuroprotective mechanisms remain unknown. Our study investigated the potential mechanisms through which curcumin ameliorates Parkinson's disease via the microbiota-gut-brain axis. Methods: Mice were randomly divided into four groups: control, Curcumin, MPTP, and MPTP + Curcumin. Motor deficits and gastrointestinal dysfunction were assessed using behavioral test, intestinal motility test, and fecal parameter measurement. The loss of dopaminergic neurons and intestinal barrier function was measured using Western blot and immunofluorescence. Shotgun metagenomic sequencing and LC-MS were parallelly performed on mice feces to investigate alterations in microbiota and metabolites. Results: Curcumin alleviated motor deficits and the loss of dopaminergic neurons in MPTP-induced mice. Curcumin ameliorated gastrointestinal and intestinal barrier dysfunctions in MPTP-induced mice. Curcumin reduced gut microbial dysbiosis and modulated carbohydrate metabolism in MPTP-induced mice. Curcumin restored short-chain fatty acid (SCFA) profiles in MPTP-induced mice. Conclusion: Concurrently, these results indicate that curcumin inhibits Parkinson's disease by regulating the gut microbiota and short-chain fatty acids.