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Frontiers in Microbiology 2023Increasing evidence from observational studies and clinical experimentation has indicated a link between the gut microbiotas (GMs) and polycystic ovary syndrome (PCOS),...
BACKGROUND
Increasing evidence from observational studies and clinical experimentation has indicated a link between the gut microbiotas (GMs) and polycystic ovary syndrome (PCOS), however, the causality and direction of causality between gut microbiome and PCOS remains to be established.
METHODS
We conducted a comprehensive search of four databases-PubMed, Cochrane Library, Web of Science, and Embase up until June 1, 2023, and subjected the results to a meta-analysis. In this study, a bidirectional two-sample Mendelian randomization (MR) analysis was employed to investigate the impact of gut microbiota on polycystic ovary syndrome (PCOS). The genome-wide association study (GWAS) data for PCOS comprised 113,238 samples, while the GWAS data for gut microbiota were derived from the MiBioGen consortium, encompassing a total sample size of 18,340 individuals. As the largest dataset of its kind, this study represents the most comprehensive genome-wide meta-analysis concerning gut microbiota composition to date. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables at various taxonomic levels, including Phylum, Class, Order, Family, and Genus. The causal associations between exposures and outcomes were assessed using four established MR methods. To correct for multiple testing, the false discovery rate (FDR) method was applied. The reliability and potential biases of the results were evaluated through sensitivity analysis and F-statistics.
RESULTS
The meta-analysis incorporated a total of 20 studies that met the criteria, revealing a close association between PCOS and specific gut microbiota species. As per the results from our MR analysis, we identified six causal associations between the gut microbiome and polycystic ovary syndrome (PCOS). At the genus level, (OR = 1.369, = 0.040), (OR = 1.548, = 0.027), and (OR = 1.488, = 0.028) were identified as risk factors for PCOS. Conversely, (OR = 0.723, = 0.040), (OR = 0.580, = 0.032), and (OR = 0.732, = 0.030) were found to be protective factors against PCOS. Furthermore, the MR-PRESSO global test and MR-Egger regression indicated that our study results were not affected by horizontal pleiotropy ( > 0.05). Finally, the leave-one-out analysis corroborated the robustness of the MR findings.
CONCLUSION
Both our meta-analysis and MR study indicates that there is a causal relationship between the gut microbiome and PCOS, which may contribute to providing novel insights for the development of new preventive and therapeutic strategies for PCOS.
PubMed: 37555058
DOI: 10.3389/fmicb.2023.1203902 -
Nature Communications Nov 2023The gut microbiota may have an effect on the therapeutic resistance and toxicity of immune checkpoint inhibitors (ICIs). However, the associations between the highly...
The gut microbiota may have an effect on the therapeutic resistance and toxicity of immune checkpoint inhibitors (ICIs). However, the associations between the highly variable genomes of gut bacteria and the effectiveness of ICIs remain unclear, despite the fact that merely a few gene mutations between similar bacterial strains may cause significant phenotypic variations. Here, using datasets from the gut microbiome of 996 patients from seven clinical trials, we systematically identify microbial genomic structural variants (SVs) using SGV-Finder. The associations between SVs and response, progression-free survival, overall survival, and immune-related adverse events are systematically explored by metagenome-wide association analysis and replicated in different cohorts. Associated SVs are located in multiple species, including Akkermansia muciniphila, Dorea formicigenerans, and Bacteroides caccae. We find genes that encode enzymes that participate in glucose metabolism be harbored in these associated regions. This work uncovers a nascent layer of gut microbiome heterogeneity that is correlated with hosts' prognosis following ICI treatment and represents an advance in our knowledge of the intricate relationships between microbiota and tumor immunotherapy.
Topics: Humans; Gastrointestinal Microbiome; Immune Checkpoint Inhibitors; Microbiota; Metagenome; Bacteria; Neoplasms
PubMed: 37973916
DOI: 10.1038/s41467-023-42997-7 -
Frontiers in Cellular and Infection... 2023Insomnia is the second most common mental health issue, also is a social and financial burden. Insomnia affects the balance between sleep, the immune system, and the...
INTRODUCTION
Insomnia is the second most common mental health issue, also is a social and financial burden. Insomnia affects the balance between sleep, the immune system, and the central nervous system, which may raise the risk of different systemic disorders. The gut microbiota, referred to as the "second genome," has the ability to control host homeostasis. It has been discovered that disruption of the gut-brain axis is linked to insomnia.
METHODS
In this study, we conducted MR analysis between large-scale GWAS data of GMs and insomnia to uncover potential associations.
RESULTS
Ten GM taxa were detected to have causal associations with insomnia. Among them, class , genus , genus , genus , genus , and order were linked to a higher risk of insomnia. In reverse MR analysis, we discovered a causal link between insomnia and six other GM taxa.
CONCLUSION
It suggested that the relationship between insomnia and intestinal flora was convoluted. Our findings may offer beneficial biomarkers for disease development and prospective candidate treatment targets for insomnia.
Topics: Humans; Gastrointestinal Microbiome; Sleep Initiation and Maintenance Disorders; Mendelian Randomization Analysis; Central Nervous System; Clostridiaceae; Genome-Wide Association Study
PubMed: 38089822
DOI: 10.3389/fcimb.2023.1296417 -
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 -
Aging Sep 2023Recent studies have shown that gut microbiota (GM) is related to hypertensive disorders in pregnancy (HDP). However, the causal relationship needs to be treated with...
BACKGROUND
Recent studies have shown that gut microbiota (GM) is related to hypertensive disorders in pregnancy (HDP). However, the causal relationship needs to be treated with caution due to confounding factors and reverse causation.
METHODS
We obtained genetic variants from genome-wide association studies including GM (N = 18,340) in MiBioGen Consortium as well as HDP (7,686 cases/115,893 controls) and specific subtypes in FinnGen Consortium. Then, Inverse variance weighted, maximum likelihood, weighted median, MR-Egger, and MR.RAPS methods were applied to examine the causal association. Reverse Mendelian randomization (RMR) and multivariable MR were performed to confirm the causal direction and adjust the potential confounders, respectively. Furthermore, sensitivity analyses including Cochran's Q statistics, MR-Egger intercept, MR-PRESSO global test, and the leave-one-out analysis were conducted to detect the potential heterogeneity and horizontal pleiotropy.
RESULTS
The present study found causalities between eight gut microbial genera and HDP. The HDP-associated gut microbial genera identified by MR analyses varied in different subtypes. Specifically, our study found causal associations of , , , , and with GH, of (), (), , , and with PE, and of and with eclampsia, respectively.
CONCLUSIONS
This study first applied the MR approach to detect the causal relationships between GM and specific HDP subtypes. Our findings may promote the prevention and treatment of HDP targeted on GM and provide valuable insights to understand the mechanism of HDP in different subtypes from the perspective of GM.
Topics: Female; Pregnancy; Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Hypertension, Pregnancy-Induced; Mendelian Randomization Analysis
PubMed: 37698537
DOI: 10.18632/aging.205019 -
Signal Transduction and Targeted Therapy Sep 2023The role of gut microbiota in modulating the durability of COVID-19 vaccine immunity is yet to be characterised. In this cohort study, we collected blood and stool...
The role of gut microbiota in modulating the durability of COVID-19 vaccine immunity is yet to be characterised. In this cohort study, we collected blood and stool samples of 121 BNT162b2 and 40 CoronaVac vaccinees at baseline, 1 month, and 6 months post vaccination (p.v.). Neutralisation antibody, plasma cytokine and chemokines were measured and associated with the gut microbiota and metabolome composition. A significantly higher level of neutralising antibody (at 6 months p.v.) was found in BNT162b2 vaccinees who had higher relative abundances of Bifidobacterium adolescentis, Bifidobacterium bifidum, and Roseburia faecis as well as higher concentrations of nicotinic acid (Vitamin B) and γ-Aminobutyric acid (P < 0.05) at baseline. CoronaVac vaccinees with high neutralising antibodies at 6 months p.v. had an increased relative abundance of Phocaeicola dorei, a lower relative abundance of Faecalibacterium prausnitzii, and a higher concentration of L-tryptophan (P < 0.05) at baseline. A higher antibody level at 6 months p.v. was also associated with a higher relative abundance of Dorea formicigenerans at 1 month p.v. among CoronaVac vaccinees (Rho = 0.62, p = 0.001, FDR = 0.123). Of the species altered following vaccination, 79.4% and 42.0% in the CoronaVac and BNT162b2 groups, respectively, recovered at 6 months. Specific to CoronaVac vaccinees, both bacteriome and virome diversity depleted following vaccination and did not recover to baseline at 6 months p.v. (FDR < 0.1). In conclusion, this study identified potential microbiota-based adjuvants that may extend the durability of immune responses to SARS-CoV-2 vaccines.
Topics: Humans; COVID-19 Vaccines; Gastrointestinal Microbiome; BNT162 Vaccine; Cohort Studies; COVID-19; SARS-CoV-2; Antibodies, Neutralizing
PubMed: 37743379
DOI: 10.1038/s41392-023-01629-8 -
Cells Jun 2023Multiple sclerosis (MS) is a chronic, progressive neuroinflammatory disease with a complex pathophysiological background. A variety of diverse factors have been... (Review)
Review
Multiple sclerosis (MS) is a chronic, progressive neuroinflammatory disease with a complex pathophysiological background. A variety of diverse factors have been attributed to the propagation of inflammation and neurodegeneration in MS, mainly genetic, immunological, and environmental factors such as vitamin D deficiency, infections, or hormonal disbalance. Recently, the importance of the gut-brain axis for the development of many neurological conditions, including stroke, movement disorders, and neuroinflammatory disorders, has been postulated. The purpose of our paper was to summarize current evidence confirming the role of the gut microbiome in the pathophysiology of MS and related disorders, such as neuromyelitis optica spectrum disorder (NMO-SD). For this aim, we conducted a systematic review of the literature listed in the following databases: Medline, Pubmed, and Scopus, and were able to identify several studies demonstrating the involvement of the gut microbiome in the pathophysiology of MS and NMO-SD. It seems that the most relevant bacteria for the pathophysiology of MS are those belonging to , , , , , , , and , while and have been demonstrated to play a role in the pathophysiology of NMO-SD. Following this line of evidence, there is also some preliminary data supporting the use of probiotics or other agents affecting the microbiome that could potentially have a beneficial effect on MS/NMO-SD symptoms and prognosis. The topic of the gut microbiome in the pathophysiology of MS is therefore relevant since it could be used as a biomarker of disease development and progression as well as a potential disease-modifying therapy.
Topics: Humans; Multiple Sclerosis; Gastrointestinal Microbiome; Neuromyelitis Optica; Vitamin D Deficiency; Inflammation
PubMed: 37443793
DOI: 10.3390/cells12131760 -
Frontiers in Cellular and Infection... 2023In recent years, observational studies have provided evidence supporting a potential association between autism spectrum disorder (ASD) and gut microbiota. However, the...
BACKGROUND
In recent years, observational studies have provided evidence supporting a potential association between autism spectrum disorder (ASD) and gut microbiota. However, the causal effect of gut microbiota on ASD remains unknown.
METHODS
We identified the summary statistics of 206 gut microbiota from the MiBioGen study, and ASD data were obtained from the latest Psychiatric Genomics Consortium Genome-Wide Association Study (GWAS). We then performed Mendelian randomization (MR) to determine a causal relationship between the gut microbiota and ASD using the inverse variance weighted (IVW) method, simple mode, MR-Egger, weighted median, and weighted model. Furthermore, we used Cochran's Q test, MR-Egger intercept test, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and leave-one-out analysis to identify heterogeneity and pleiotropy. Moreover, the Benjamin-Hochberg approach (FDR) was employed to assess the strength of the connection between exposure and outcome. We performed reverse MR analysis on the gut microbiota that were found to be causally associated with ASD in the forward MR analysis to examine the causal relationships. The enrichment analyses were used to analyze the biological function at last.
RESULTS
Based on the results of IVW results, genetically predicted and had a possible positive association with ASD (IVW OR=1.14, 95% CI: 1.00-1.29, =3.7×10), four gut microbiota with a potential protective effect on ASD: (OR=0.81, 95% CI: 0.69-0.96, =1.4×10), (OR=0.81, 95% CI: 0.69-0.96, =1.5×10), (OR=0.83, 95% CI: 0.70-0.98, =2.8×10), and (OR=0.82, 95% CI: 0.68-0.99, =3.6×10). After FDR multiple-testing correction we further observed that there were two gut microbiota still have significant relationship with ASD: (IVW OR=1.24; 95% CI: 1.09-1.40, =9.2×10) was strongly positively correlated with ASD and (IVW OR=0.78, 95% CI: 0.67-0.89, =6.9×10) was strongly negatively correlated with ASD. The sensitivity analysis excluded the influence of heterogeneity and horizontal pleiotropy.
CONCLUSION
Our findings reveal a causal association between several gut microbiomes and ASD. These results deepen our comprehension of the role of gut microbiota in ASD's pathology, providing the foothold for novel ideas and theoretical frameworks to prevent and treat this patient population in the future.
Topics: Humans; Gastrointestinal Microbiome; Autism Spectrum Disorder; Genome-Wide Association Study; Mendelian Randomization Analysis; Bacteroidetes
PubMed: 38156319
DOI: 10.3389/fcimb.2023.1267721 -
Genome Biology Oct 2023The gut microbiota plays a crucial role in regulating host metabolism and producing uremic toxins in patients with end-stage renal disease (ESRD). Our objective is to...
BACKGROUND
The gut microbiota plays a crucial role in regulating host metabolism and producing uremic toxins in patients with end-stage renal disease (ESRD). Our objective is to advance toward a holistic understanding of the gut ecosystem and its functional capacity in such patients, which is still lacking.
RESULTS
Herein, we explore the gut microbiome of 378 hemodialytic ESRD patients and 290 healthy volunteers from two independent cohorts via deep metagenomic sequencing and metagenome-assembled-genome-based characterization of their feces. Our findings reveal fundamental alterations in the ESRD microbiome, characterized by a panel of 348 differentially abundant species, including ESRD-elevated representatives of Blautia spp., Dorea spp., and Eggerthellaceae, and ESRD-depleted Prevotella and Roseburia species. Through functional annotation of the ESRD-associated species, we uncover various taxon-specific functions linked to the disease, such as antimicrobial resistance, aromatic compound degradation, and biosynthesis of small bioactive molecules. Additionally, we show that the gut microbial composition can be utilized to predict serum uremic toxin concentrations, and based on this, we identify the key toxin-contributing species. Furthermore, our investigation extended to 47 additional non-dialyzed chronic kidney disease (CKD) patients, revealing a significant correlation between the abundance of ESRD-associated microbial signatures and CKD progression.
CONCLUSION
This study delineates the taxonomic and functional landscapes and biomarkers of the ESRD microbiome. Understanding the role of gut microbiota in ESRD could open new avenues for therapeutic interventions and personalized treatment approaches in patients with this condition.
Topics: Humans; Metagenome; Gastrointestinal Microbiome; Kidney Failure, Chronic; Microbiota; Renal Insufficiency, Chronic; Feces; Clostridiales
PubMed: 37828586
DOI: 10.1186/s13059-023-03056-y -
Journal of Gastrointestinal and Liver... Sep 2023Traditional cardiovascular risk factors are established predictors of heart failure (HF). However, the human gut microbiota is suggested to potentially interact with the...
BACKGROUND AND AIMS
Traditional cardiovascular risk factors are established predictors of heart failure (HF). However, the human gut microbiota is suggested to potentially interact with the cardiovascular system through the "gut-heart axis", which induces inflammation and contributes to HF pathogenesis. This systematic review aims to confirm the interconnection between the gut microbiome in HF patients.
METHODS
Peer-reviewed human studies comparing the gut microbiota profile in adult patients with HF and healthy controls (HCs) up to April 18, 2022, were searched in Ovid MEDLINE, Ovid EMBASE, SCOPUS, and the Cochrane Library. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS).
RESULTS
A total of nine studies, including 317 HF patients and 510 HCs, were included in the review. Decreased gut microbiota richness and similar microbial diversity (alpha diversity), and significantly different gut microbiota composition (beta diversity) were observed between HF patients and HCs. In comparison to HCs, HF patients had a greater abundance of Actinobacteria, Proteobacteria, and Synergistetes phyla; Enterococcus, Escherichia, Klebsiella, Lactobacillus, Streptococcus, and Veilonella genera and Ruminococcus gnavus, Streptococcus sp., and Veilonella sp. species. In contrast, there was decreased abundance of Firmicutes phylum; Blautia, Eubacterium, Faecalibacterium, and Lachnospiraceae FCS020 genera; and Dorea longicatena, Eubacterium rectale, Faecalibacterium prausnitzii, Oscillibacter sp., and Sutterella wadsworthensis species in HF patients.
CONCLUSIONS
Gut microbiota diversity, richness, and composition in HF patients differ significantly from the healthy population. Overall, short-chain fatty acid (SCFA)-producing gut microbiota was depleted in HF patients. However, different underlying comorbidities, environments, lifestyles, and dietary choices could affect gut microbiota heterogeneity.
Topics: Adult; Humans; Gastrointestinal Microbiome; Diet; Bacteria; Heart Failure; Inflammation
PubMed: 37774217
DOI: 10.15403/jgld-4779