Gut microbiota and risk of five common cancers: A univariable and multivariable Mendelian randomization study

Cancer Medicine, Journal Year: 2023, Volume and Issue: 12(9), P. 10393 - 10405

Published: March 7, 2023

Previous studies have linked gut microbiota with cancer etiology, but the associations for specific are causal or owing to bias remain be elucidated.We performed a two-sample Mendelian randomization (MR) analysis assess effect of on risk. Five common cancers, including breast, endometrial, lung, ovarian, and prostate as well their subtypes (sample sizes ranging from 27,209 228,951) were included outcomes. Genetic information was obtained genome-wide association study (GWAS) comprising 18,340 participants. In univariable MR (UVMR) analysis, inverse variance weighted (IVW) method conducted primary method, robust adjusted profile scores, median, Egger used supplementary methods inference. Sensitivity analyses Cochran Q test, intercept leave-one-out verify robustness results. Multivariable (MVMR) evaluate direct effects risk cancers.UVMR detected higher abundance genus Sellimonas predicted estrogen receptor-positive breast (OR = 1.09, 95% CI 1.05-1.14, p 2.01 × 10-5 ), class Alphaproteobacteria associated lower 0.84, 0.75-0.93, 1.11 10-3 ). found little evidence in current study. MVMR further confirmed that exerted cancer, while driven by factors cancer.Our implies involvement development, which provides novel potential target screening prevention, might an implication future functional analysis.

Language: Английский

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Causal effects of exposure to ambient air pollution on cancer risk: Insights from genetic evidence

The Science of The Total Environment, Journal Year: 2023, Volume and Issue: 912, P. 168843 - 168843

Published: Nov. 28, 2023

Language: Английский

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Causal relationship between gut microbiota and gastrointestinal diseases: a mendelian randomization study

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 23, 2024

Abstract Background Recent research increasingly highlights a strong correlation between gut microbiota and the risk of gastrointestinal diseases. However, whether this relationship is causal or merely coincidental remains uncertain. To address this, Mendelian randomization (MR) analysis was undertaken to explore connections prevalent Methods Genome-wide association study (GWAS) summary statistics for microbiota, encompassing diverse range 211 taxa (131 genera, 35 families, 20 orders, 16 classes, 9 phyla), were sourced from comprehensive MiBioGen study. Genetic associations with 22 diseases gathered UK Biobank, FinnGen study, various extensive GWAS studies. MR meticulously conducted assess genetically predicted these validate reliability our findings, sensitivity analyses tests heterogeneity systematically performed. Results The yielded significant evidence 251 relationships This included 98 upper diseases, 81 lower 54 hepatobiliary 18 pancreatic Notably, particularly evident in belonging genera Ruminococcus Eubacterium . Further reinforced robustness results. Conclusions findings indicate potential genetic predisposition linking These insights pave way designing future clinical trials focusing on microbiome-related interventions, including use microbiome-dependent metabolites, potentially treat manage their associated factors.

Language: Английский

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Gut–X axis

iMeta, Journal Year: 2025, Volume and Issue: 4(1)

Published: Feb. 1, 2025

Abstract Recent advances in understanding the modulatory functions of gut and microbiota on human diseases facilitated our focused attention contribution to pathophysiological alterations many extraintestinal organs, including liver, heart, brain, lungs, kidneys, bone, skin, reproductive, endocrine systems. In this review, we applied “gut–X axis” concept describe linkages between other organs discussed latest findings related axis,” underlying mechanisms potential clinical intervention strategies.

Language: Английский

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Potential causal association between gut microbiome and posttraumatic stress disorder

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 31, 2024

Abstract Background The causal effects of gut microbiome and the development posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential association using mendelian randomization (MR). Methods summary-level statistics for were retrieved from a genome-wide (GWAS) MiBioGen consortium. As PTSD, Freeze 2 datasets originated Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), replicated obtained FinnGen Single nucleotide polymorphisms meeting MR assumptions selected as instrumental variables. inverse variance weighting (IVW) method was employed main approach, supplemented by sensitivity analyses evaluate pleiotropy heterogeneity ensure robustness results. We also performed reverse explore PTSD’s on relative abundances specific features microbiome. Results In PGC-PTSD, eight bacterial traits revealed between PTSD (IVW, all P < 0.05). addition, Genus.Dorea genus.Sellimonas in datasets, which occurrence PTSD. further supported IVW findings, providing additional evidence reliability. Conclusion Our provides impact microbiomes shedding new light understanding dysfunctional gut-brain axis this disorder. findings present novel call investigations confirm links, well illuminate underlying mechanisms.

Language: Английский

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Risk factors for prostate cancer: An umbrella review of prospective observational studies and mendelian randomization analyses

PLoS Medicine, Journal Year: 2024, Volume and Issue: 21(3), P. e1004362 - e1004362

Published: March 15, 2024

Background The incidence of prostate cancer is increasing in older males globally. Age, ethnicity, and family history are identified as the well-known risk factors for cancer, but few modifiable have been firmly established. objective this study was to identify evaluate various modifying reported meta-analyses prospective observational studies mendelian randomization (MR) analyses. Methods findings We searched PubMed, Embase, Web Science from inception January 10, 2022, updated on September 9, 2023, MR cancer. Eligibility criteria were (1) including or that declared outcome-free at baseline; (2) evaluating any category associated with incidence; (3) providing effect estimates further data synthesis. Similar applied studies. Meta-analysis repeated using random-effects inverse-variance model DerSimonian—Laird method. Quality assessment then conducted included AMSTAR-2 tool STROBE-MR assumption evaluation. Subsequent evidence grading significant associations contained sample size, P values 95% confidence intervals, prediction heterogeneity, publication bias, assigning 4 grades (convincing, highly suggestive, weak). Significant graded robust, probable, insufficient considering concordance directions. Finally, 92 selected 411 64 118 after excluding overlapping outdated which published earlier fewer participants instrument variables same exposure. In total, 123 (45 78 null) 145 causal (55 90 categorized into lifestyle; diet nutrition; anthropometric indices; biomarkers; clinical variables, diseases, treatments; environmental factors. Concerning associations, there 5 36 weak meta-analyses, 10 24 17 Twenty-six between identified, consistent effects found physical activity (PA) (occupational PA meta: OR = 0.87, CI: 0.80, 0.94; accelerator-measured MR: 0.49, 0.33, 0.72), height (meta: 1.09, 1.06, 1.12; 1.07, 1.01, 1.15, aggressive cancer), smoking (current 0.74, 0.68, 0.80; initiation 0.91, 0.86, 0.97). Methodological limitation could be expanded by more indices. Conclusions large-scale study, we summarized provided comparisons meta-analysis genetically estimated causality absence convincing based existing literature, no robust some observed height, activity, smoking.

Language: Английский

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Gut Microbiota–Tumor Microenvironment Interactions: Mechanisms and Clinical Implications for Immune Checkpoint Inhibitor Efficacy in Cancer

Cancer Management and Research, Journal Year: 2025, Volume and Issue: Volume 17, P. 171 - 192

Published: Jan. 1, 2025

Cancer immunotherapy has transformed cancer treatment in recent years, with immune checkpoint inhibitors (ICIs) emerging as a key therapeutic approach. ICIs work by inhibiting the mechanisms that allow tumors to evade detection. Although have shown promising results, especially solid tumors, patient responses vary widely due multiple intrinsic and extrinsic factors within tumor microenvironment. Emerging evidence suggests gut microbiota plays pivotal role modulating at site may even influence outcomes patients receiving ICIs. This review explores complex interactions between microenvironment, examining how these could impact effectiveness of ICI therapy. Furthermore, we discuss dysbiosis, an imbalance composition, contribute resistance ICIs, highlight microbiota-targeted strategies potentially overcome this challenge. Additionally, studies investigating diagnostic potential profiles patients, considering microbial markers might aid early detection stratification By integrating insights from preclinical clinical studies, aim shed light on microbiome modulation adjunct tool, paving way for personalized approaches optimize outcomes.

Language: Английский

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Investigating the causal relationship of gut microbiota with GERD and BE: a bidirectional mendelian randomization

BMC Genomics, Journal Year: 2024, Volume and Issue: 25(1)

Published: May 14, 2024

Gut microbiota(GM) have been proven associated with lots of gastrointestinal diseases, but its causal relationship Gastroesophageal reflux disease(GERD) and Barrett's esophagus(BE) hasn't explored. We aimed to uncover the relation between GM GERD/BE potential mediators by utilizing Mendelian Randomization(MR) analysis.

Language: Английский

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Revealing a causal relationship between gut microbiota and lung cancer: a Mendelian randomization study

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Sept. 27, 2023

The gut microbiota has been found to be associated with the risk of lung cancer. However, its causal relationship various types cancer remains unclear.We conducted a Mendelian randomization (MR) study using largest genome-wide association analysis data date from MiBioGen consortium, pooled statistics for Transdisciplinary Research in Cancer Lung, International Lung Consortium, and FinnGen Consortium R7 release data. Inverse variance weighted, weighted model, MR-Egger regression, median were adapted assess between Sensitivity was used test presence pleiotropy heterogeneity instrumental variables. A reverse MR performed on these bacteria determine their potential role causing Multivariable (MVMR) direct impact cancer.Using IVW as primary analytical method, we identified total 40 groups associations subtypes cancer, which 10 adenocarcinoma, 9 squamous cell 11 small After performing FDR correction, further that there still significant Peptococcaceae adenocarcinoma. analyses demonstrated robustness results, no or found.Our results confirm specific providing new insights into mediating development

Language: Английский

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The association between gut microbiome and PCOS: evidence from meta-analysis and two-sample mendelian randomization

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: July 24, 2023

Increasing evidence from observational studies and clinical experimentation has indicated a link between the gut microbiotas (GMs) polycystic ovary syndrome (PCOS), however, causality direction of microbiome PCOS remains to be established. We conducted comprehensive search four databases-PubMed, Cochrane Library, Web Science, Embase up until June 1, 2023, subjected results meta-analysis. In this study, bidirectional two-sample Mendelian randomization (MR) analysis was employed investigate impact microbiota on (PCOS). The genome-wide association study (GWAS) data for comprised 113,238 samples, while GWAS were derived MiBioGen consortium, encompassing total sample size 18,340 individuals. As largest dataset its kind, represents most meta-analysis concerning composition date. Single nucleotide polymorphisms (SNPs) selected as instrumental variables at various taxonomic levels, including Phylum, Class, Order, Family, Genus. causal associations exposures outcomes assessed using established MR methods. To correct multiple testing, false discovery rate (FDR) method applied. reliability potential biases evaluated through sensitivity F-statistics. incorporated 20 that met criteria, revealing close specific species. per our analysis, we identified six At genus level, Actinomyces (ORIVW = 1.369, FDR 0.040), Streptococcus 1.548, 0.027), Ruminococcaceae UCG-005 1.488, 0.028) risk factors PCOS. Conversely, Candidatus Soleaferrea 0.723, Dorea 0.580, 0.032), UCG-011 0.732, 0.030) found protective against Furthermore, MR-PRESSO global test MR-Egger regression not affected by horizontal pleiotropy (p > 0.05). Finally, leave-one-out corroborated robustness findings. Both indicates there is relationship PCOS, which may contribute providing novel insights development new preventive therapeutic strategies

Language: Английский

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