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Journal of Affective Disorders May 2023Several studies have linked gut microbiota to human brain activity. This study used Mendelian randomization (MR) to investigate the causal relationship between gut...
BACKGROUND
Several studies have linked gut microbiota to human brain activity. This study used Mendelian randomization (MR) to investigate the causal relationship between gut microbes and delirium.
METHODS
MR was used to select SNPs from large-scale GWAS summary data on 211 gut microbiota taxa and delirium. Inverse variance weighting (IVW), weighted median, and MR-Egger methods were used for statistical analyses. Outliers were assessed using the leave-one-out method. To avoid horizontal pleiotropy, we performed the MR-PRESSO and MR-Egger intercept tests. Cochran's Q and I values for IVW and MR-Egger were used to assess heterogeneity.
RESULTS
IVW suggested that genetic prediction of the family Desulfovibrionaceae (1.784 (1.267-2.512), P = 0.001), order Desulfovibrionales (1.501 (1.058-2.128), P = 0.023), and genus Candidatus Soleaferrea (1.322 (1.052-1.659), P = 0.016) increased the risk of delirium, but the family Oxalobacteraceae (0.841 (0.722-0.981), P = 0.027), and genera Holdemania (0.766 (0.620-0.946), P = 0.013), Ruminococcus gnavus (0.806 (0.661-0.982), P = 0.033), and Eggerthella (0.815 (0.667-0.997), P = 0.047) reduced the risk of delirium.
LIMITATIONS
(1) Limited sample size, (2) inability to assess gut microbiota interactions, and (3) limited to European populations.
CONCLUSION
Our results suggest that presence of the microbial family Desulfovibrionaceae, order Desulfovibrionales, and genus Candidatus Soleaferrea increased the risk of delirium, whereas the Oxalobacteraceae family, and the genera Holdemania, Ruminococcus gnavus, and Eggerthella decreased the risk of delirium. However, the potential of gut probiotic interventions in the prevention of perioperative delirium should be emphasized.
Topics: Humans; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Causality; Delirium; Genome-Wide Association Study
PubMed: 36842654
DOI: 10.1016/j.jad.2023.02.078 -
Brain, Behavior, and Immunity Oct 2020Growing evidences show that gut microbiota is associated with the pathogenesis of Parkinson's disease (PD) and the gut-brain axis can be promising target for the...
Growing evidences show that gut microbiota is associated with the pathogenesis of Parkinson's disease (PD) and the gut-brain axis can be promising target for the development of the therapeutic strategies for PD. Acupuncture has been used to improve brain functions and inflammation in neurological disorders such as PD, and to recover the gastrointestinal dysfunctions in various gastrointestinal disorders. Thus, we investigated whether acupuncture could improve Parkinsonism and gut microbial dysbiosis induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. First, we observed that acupuncture treatment at acupoints GB34 and ST36 could improve motor functions and comorbid anxiety in PD mice. Next, we found that acupuncture increased the levels of dopaminergic fibers and neurons in the striatum and the substantia nigra, respectively. Acupuncture also restored the overexpression of microglia and astrocyte as well as conversion of Bax and Bcl-2 expression in both the striatum and the substantia nigra, indicating that inflammatory responses and apoptosis were blocked by acupuncture. Additionally, via 16S rRNA sequence analysis, we observed that the relative abundance of 18 genera were changed in acupuncture-treated mice compared to the PD mice. Of them, Butyricimonas, Holdemania, Frisingicoccus, Gracilibacter, Phocea, and Aestuariispira showed significant correlations with anxiety as well as motor functions. Furthermore, the predicted functional analyses showed that acupuncture restored the physiology functions such as glutathione metabolism, methane metabolism, and PD pathway. In conclusion, we suggest that the effects of acupuncture on the enhanced motor function and the protection of the dopaminergic neurons may be associated with the regulation of the gut microbial dysbiosis and thus the inhibition of the neuroinflammation in the PD mice.
Topics: Acupuncture Therapy; Animals; Disease Models, Animal; Dopaminergic Neurons; Dysbiosis; Gastrointestinal Microbiome; Mice; Mice, Inbred C57BL; Parkinson Disease; RNA, Ribosomal, 16S; Substantia Nigra
PubMed: 32827699
DOI: 10.1016/j.bbi.2020.08.015 -
Frontiers in Psychiatry 2020Cumulative evidence shows a linkage between gut microbiota pattern and depression through the brain-gut microbiome axis. The aim of this systematic review was to...
Cumulative evidence shows a linkage between gut microbiota pattern and depression through the brain-gut microbiome axis. The aim of this systematic review was to identify the alterations of the gut microbiota patterns in people with depression compared to healthy controls. A comprehensive literature search of human studies, published between January 2000 and June 2019, was reviewed. The key words included gastrointestinal microbiome, gut microbiome, microbiota, depression, depressive symptoms, and depressive disorder. The systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Nine articles met the eligibility criteria. Disparities in α-diversity and β-diversity of the microbiota existed in people with depression compared to healthy controls. At the phylum level, there were inconsistencies in the abundance of , , . However, high abundance in and phyla were observed in people with depression. On the family level, high abundance of , , , , , , , , , , , , , low abundance of , , , , , , and were observed in people with depression. On the genus level, high abundance of , , , , , , , , , , , , , , , , , , , , , , , and low abundance of , , , , , , , and were found in people with depression. Alteration of gut microbiome patterns was evident in people with depression. Further evidence is warranted to allow for the translation of microbiome findings toward innovative clinical strategies that may improve treatment outcomes in people with depression.
PubMed: 32587537
DOI: 10.3389/fpsyt.2020.00541 -
Neoplasia (New York, N.Y.) Oct 2017This is the first prospective study of the effects of human gut microbiota and metabolites on immune checkpoint inhibitor (ICT) response in metastatic melanoma patients....
Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients.
This is the first prospective study of the effects of human gut microbiota and metabolites on immune checkpoint inhibitor (ICT) response in metastatic melanoma patients. Whereas many melanoma patients exhibit profound response to ICT, there are fewer options for patients failing ICT-particularly with BRAF-wild-type disease. In preclinical studies, specific gut microbiota promotes regression of melanoma in mice. We therefore conducted a study of the effects of pretreatment gut microbiota and metabolites on ICT Response Evaluation Criteria in Solid Tumors response in 39 metastatic melanoma patients treated with ipilimumab, nivolumab, ipilimumab plus nivolumab (IN), or pembrolizumab (P). IN yielded 67% responses and 8% stable disease; P achieved 23% responses and 23% stable disease. ICT responders for all types of therapies were enriched for Bacteroides caccae. Among IN responders, the gut microbiome was enriched for Faecalibacterium prausnitzii, Bacteroides thetaiotamicron, and Holdemania filiformis. Among P responders, the microbiome was enriched for Dorea formicogenerans. Unbiased shotgun metabolomics revealed high levels of anacardic acid in ICT responders. Based on these pilot studies, both additional confirmatory clinical studies and preclinical testing of these bacterial species and metabolites are warranted to confirm their ICT enhancing activity.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Immunological; Biomarkers, Tumor; Chromatography, High Pressure Liquid; Cluster Analysis; Female; Gastrointestinal Microbiome; High-Throughput Nucleotide Sequencing; Humans; Male; Melanoma; Metabolomics; Metagenome; Metagenomics; Middle Aged; Molecular Targeted Therapy; Neoplasm Metastasis; Neoplasm Staging; Prognosis; Tandem Mass Spectrometry; Treatment Outcome
PubMed: 28923537
DOI: 10.1016/j.neo.2017.08.004 -
Frontiers in Microbiology 2023Observational studies have provided evidence of a close association between gut microbiota and the progression of chronic hepatitis B (CHB). However, establishing a...
BACKGROUND
Observational studies have provided evidence of a close association between gut microbiota and the progression of chronic hepatitis B (CHB). However, establishing a causal relationship between gut microbiota and CHB remains a subject of investigation.
METHODS
Genome-wide association study (GWAS) summary data of gut microbiota came from the MiBioGen consortium, while the GWAS summary data of CHB came from the Medical Research Council Integrative Epidemiology Unit (IEU) Open GWAS project. Based on the maximum likelihood (ML), Mendelian randomization (MR)-Egger regression, inverse variance weighted (IVW), MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and weighted-mode and weighted-median methods, we conducted a bidirectional, two-sample, MR analysis to explore the causal relationship between the gut microbiota and CHB. Additionally, we evaluated the genetic associations between individual gut microbes and CHB using the Linkage disequilibrium score regression (LDSC) program.
RESULTS
According to the IVW method estimates, genetically predicted class Alphaproteobacteria (odds ratio [OR] = 0.57; 95% confidence interval [CI], 0.34-0.96; false discovery rate [FDR] = 0.046), genus group (OR = 0.60; 95% CI, 0.39-0.91; FDR = 0.026), genus (OR = 0.73; 95% CI, 0.56-0.94; FDR = 0.022) exhibited a protective effect against CHB. On the other hand, family Family XIII (OR = 1.79; 95% CI, 1.03-3.12; FDR = 0.061), genus group (OR = 1.34; 95% CI, 1.04-1.74; FDR = 0.043), genus group (OR = 1.59; 95% CI, 1.01-2.51; FDR = 0.056), genus (OR = 1.35; 95% CI, 1.00-1.82; FDR = 0.049), and genus group (OR = 1.69; 95% CI, 1.10-2.61; FDR = 0.076) were associated with an increased risk of CHB. The results from LDSC also indicated a significant genetic correlation between most of the aforementioned gut microbiota and CHB. Our reverse MR analysis demonstrated no causal relationship between genetically predicted CHB and gut microbiota, and we observed no significant horizontal pleiotropy or heterogeneity of instrumental variables (IVs).
CONCLUSION
In this study, we identified three types of gut microbiota with a protective effect on CHB and five types with an adverse impact on CHB. We postulate that this information will facilitate the clinical prevention and treatment of CHB through fecal microbiota transplantation.
PubMed: 37655340
DOI: 10.3389/fmicb.2023.1243811 -
BMC Women's Health Nov 2023Previous studies have shown observational associations between the gut microbiota and endometriosis; however, the causal nature of such associations remains unclear....
BACKGROUND
Previous studies have shown observational associations between the gut microbiota and endometriosis; however, the causal nature of such associations remains unclear. This study aimed to analyze the genetic causal relationship between the two.
METHODS
A gut microbiome genome-wide association study conducted by the MiBioGen consortium was used as exposure data, and summary statistics of endometriosis were obtained from the FinnGen consortium R8 release data. Inverse variance weighted, MR-Egger, weighted median, weighted model, and simple model analyses were applied to examine the causal relationship, and sensitivity analyses were conducted to validate the robustness of the results.
RESULTS
The results showed that, out of 211 gut microbiome taxa, Clostridiales_vadin_BB60_group, Oxalobacteraceae, Desulfovibrio, Haemophilus, and Holdemania had protective effects on endometriosis, while Porphyromonadaceae and Anaerotruncus might contribute to the development of endometriosis. Heterogeneity and pleiotropy analyses confirmed the robustness of the results.
CONCLUSION
The two-sample Mendelian randomization analysis conducted in this study identified specific intestinal flora with a causal relationship with endometriosis at the genetic level, offering new insights into the gut microbiota-mediated development mechanism of endometriosis.
Topics: Female; Humans; Gastrointestinal Microbiome; Endometriosis; Genome-Wide Association Study; Mendelian Randomization Analysis; Microbiota
PubMed: 38037013
DOI: 10.1186/s12905-023-02742-0 -
Frontiers in Cellular and Infection... 2023The gut microbiota is closely linked to cholesterol metabolism-related diseases such as obesity and cardiovascular diseases. However, whether gut microbiota plays a...
BACKGROUND
The gut microbiota is closely linked to cholesterol metabolism-related diseases such as obesity and cardiovascular diseases. However, whether gut microbiota plays a causal role in cholelithiasis remains unclear.
AIMS
This study explored the causal relationship between gut microbiota and cholelithiasis. We hypothesize that the gut microbiota influences cholelithiasis development.
METHODS
A two-sample Mendelian randomization method was combined with STRING analysis to test this hypothesis. Summary data on gut microbiota and cholelithiasis were obtained from the MiBioGen (n=13,266) and FinnGen R8 consortia (n=334,367), respectively.
RESULTS
, , and increased the risk of cholelithiasis and expressed more bile salt hydrolases. In contrast, , , and weakly expressed bile salt hydrolases and were implied to have a protective effect against cholelithiasis by Mendelian randomization analysis.
CONCLUSION
Gut microbiota causally influences cholelithiasis and may be related to bile salt hydrolases. This work improves our understanding of cholelithiasis causality to facilitate the development of treatment strategies.
Topics: Humans; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Cardiovascular Diseases; Clostridiales; Bile Acids and Salts; Genome-Wide Association Study
PubMed: 37876873
DOI: 10.3389/fcimb.2023.1253447 -
Cardiovascular Diabetology Nov 2023Gut microbiota imbalances have been suggested as a contributing factor to atrial fibrillation (AF), but the causal relationship is not fully understood.
BACKGROUND
Gut microbiota imbalances have been suggested as a contributing factor to atrial fibrillation (AF), but the causal relationship is not fully understood.
OBJECTIVES
To explore the causal relationships between the gut microbiota and AF using Mendelian randomization (MR) analysis.
METHODS
Summary statistics were from genome-wide association studies (GWAS) of 207 gut microbial taxa (5 phyla, 10 classes, 13 orders, 26 families, 48 genera, and 105 species) (the Dutch Microbiome Project) and two large meta-GWASs of AF. The significant results were validated in FinnGen cohort and over 430,000 UK Biobank participants. Mediation MR analyses were conducted for AF risk factors, including type 2 diabetes, coronary artery disease (CAD), body mass index (BMI), blood lipids, blood pressure, and obstructive sleep apnea, to explore the potential mediation effect of these risk factors in between the gut microbiota and AF.
RESULTS
Two microbial taxa causally associated with AF: species Eubacterium ramulus (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.04-1.12, P = 0.0001, false discovery rate (FDR) adjusted p-value = 0.023) and genus Holdemania (OR 1.15, 95% CI 1.07-1.25, P = 0.0004, FDR adjusted p-value = 0.042). Genus Holdemania was associated with incident AF risk in the UK Biobank. The proportion of mediation effect of species Eubacterium ramulus via CAD was 8.05% (95% CI 1.73% - 14.95%, P = 0.008), while the proportion of genus Holdemania on AF via BMI was 12.01% (95% CI 5.17% - 19.39%, P = 0.0005).
CONCLUSIONS
This study provided genetic evidence to support a potential causal mechanism between gut microbiota and AF and suggested the mediation role of AF risk factors.
Topics: Humans; Atrial Fibrillation; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Cohort Studies; Diabetes Mellitus, Type 2; Genome-Wide Association Study; Coronary Artery Disease
PubMed: 37940997
DOI: 10.1186/s12933-023-02045-6 -
Frontiers in Microbiology 2022The gut microbiota plays a crucial role in food allergies. We sought to identify characteristics of the maternal gut microbiota in the third trimester and the infant gut...
The gut microbiota plays a crucial role in food allergies. We sought to identify characteristics of the maternal gut microbiota in the third trimester and the infant gut microbiota in early life and the association of these microbiotas with infant food allergy. A total of 68 healthy pregnant women and their full-term newborns were selected from a cohort of 202 mother-infant pairs; among them, 24 infants had been diagnosed with food allergy within 1 year of age, whereas 44 infants were healthy without allergic symptoms. We collected 65 maternal fecal samples before delivery and 253 infant fecal samples at five time points following birth. Fecal samples were microbiologically analyzed using 16S rRNA gene sequencing. abundance in the maternal gut microbiota in the third trimester was significantly higher in the non-allergy group than in the food allergy group ( = 0.036). In the infant gut microbiota, was only found in meconium samples; its abundance did not differ significantly between the two groups. The change in the abundance of over time differed between the non-allergy and food allergy groups (FA, = 0.013; NA, = 9.8 × 10), and the change in the abundance of over time differed significantly in the non-allergy group ( = 0.023). The abundances of genera , and were significantly different between the non-allergy and food allergy groups at different time points. Our results showed that maternal carriage of during the third trimester strongly predicted the absence of food allergies in infants; there was no correlation between the presence of food allergies and the abundance of in the infant gut microbiota. More dynamic fluctuations in phyla Actinobacteria and Firmicutes early in life protect against food allergy. Thus, the enrichment of the infant gut microbiota early in life with short-chain fatty acid-producing bacteria may be beneficial in preventing the development of food allergies in infants.
PubMed: 36419421
DOI: 10.3389/fmicb.2022.933152 -
Frontiers in Cellular and Infection... 2023Recent studies have suggested a relationship between gut microbiota and non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). However, the...
BACKGROUND
Recent studies have suggested a relationship between gut microbiota and non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). However, the nature and direction of this potential causal relationship are still unclear. This study used two-sample Mendelian randomization (MR) to clarify the potential causal links.
METHODS
Summary-level Genome-Wide Association Studies (GWAS) statistical data for gut microbiota and NAFLD/NASH were obtained from MiBioGen and FinnGen respectively. The MR analyses were performed mainly using the inverse-variance weighted (IVW) method, with sensitivity analyses conducted to verify the robustness. Additionally, reverse MR analyses were performed to examine any potential reverse causal associations.
RESULTS
Our analysis, primarily based on the IVW method, strongly supports the existence of causal relationships between four microbial taxa and NAFLD, and four taxa with NASH. Specifically, associations were observed between Enterobacteriales ( =0.04), ( =0.04), ( =0.02), and ( =0.04) and increased risk of NAFLD. ( =0.03) and ( =0.04) could increase the risks of NASH while ( =0.04) and (=0.005) could decrease them. We also identified that NAFLD was found to potentially cause an increased abundance in ( =0.007) and ( =0.002). However, we found no evidence of reverse causation in the microbial taxa associations with NASH.
CONCLUSION
This study identified several specific gut microbiota that are causally related to NAFLD and NASH. Observations herein may provide promising theoretical groundwork for potential prevention and treatment strategies for NAFLD and its progression to NASH in future.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Clostridiaceae; Clostridiales
PubMed: 38106475
DOI: 10.3389/fcimb.2023.1294826