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Journal of Translational Medicine Jan 2024Recent research increasingly highlights a strong correlation between gut microbiota and the risk of gastrointestinal diseases. However, whether this relationship is...
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, a Mendelian randomization (MR) analysis was undertaken to explore the connections between gut microbiota and prevalent gastrointestinal diseases.
METHODS
Genome-wide association study (GWAS) summary statistics for gut microbiota, encompassing a diverse range of 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla), were sourced from the comprehensive MiBioGen study. Genetic associations with 22 gastrointestinal diseases were gathered from the UK Biobank, FinnGen study, and various extensive GWAS studies. MR analysis was meticulously conducted to assess the causal relationship between genetically predicted gut microbiota and these gastrointestinal diseases. To validate the reliability of our findings, sensitivity analyses and tests for heterogeneity were systematically performed.
RESULTS
The MR analysis yielded significant evidence for 251 causal relationships between genetically predicted gut microbiota and the risk of gastrointestinal diseases. This included 98 associations with upper gastrointestinal diseases, 81 with lower gastrointestinal diseases, 54 with hepatobiliary diseases, and 18 with pancreatic diseases. Notably, these associations were particularly evident in taxa belonging to the genera Ruminococcus and Eubacterium. Further sensitivity analyses reinforced the robustness of these results.
CONCLUSIONS
The findings of this study indicate a potential genetic predisposition linking gut microbiota to gastrointestinal diseases. These insights pave the way for designing future clinical trials focusing on microbiome-related interventions, including the use of microbiome-dependent metabolites, to potentially treat or manage gastrointestinal diseases and their associated risk factors.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Reproducibility of Results; Gastrointestinal Diseases
PubMed: 38263233
DOI: 10.1186/s12967-024-04894-5 -
Journal of Crohn's & Colitis Nov 2023Dietary patterns are important in managing ulcerative colitis [UC], given their influence on gut microbiome-host symbiosis and inflammation. We investigated whether the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIMS
Dietary patterns are important in managing ulcerative colitis [UC], given their influence on gut microbiome-host symbiosis and inflammation. We investigated whether the Mediterranean Diet Pattern [MDP] vs the Canadian Habitual Diet Pattern [CHD] would affect disease activity, inflammation, and the gut microbiome in patients with quiescent UC.
METHODS
We performed a prospective, randomised, controlled trial in adults [65% female; median age 47 years] with quiescent UC in an outpatient setting from 2017 to 2021. Participants were randomised to an MDP [n = 15] or CHD [n = 13] for 12 weeks. Disease activity [Simple Clinical Colitis Activity Index] and faecal calprotectin [FC] were measured at baseline and week 12. Stool samples were analysed by 16S rRNA gene amplicon sequencing.
RESULTS
The diet was well tolerated by the MDP group. At week 12, 75% [9/12] of participants in the CHD had an FC >100 μg/g, vs 20% [3/15] of participants in the MDP group. The MDP group had higher levels of total faecal short chain fatty acids [SCFAs] [p = 0.01], acetic acid [p = 0.03], and butyric acid [p = 0.03] compared with the CHD. Furthermore, the MDP induced alterations in microbial species associated with a protective role in colitis [Alistipes finegoldii and Flavonifractor plautii], as well as the production of SCFAs [Ruminococcus bromii].
CONCLUSIONS
An MDP induces gut microbiome alterations associated with the maintenance of clinical remission and reduced FC in patients with quiescent UC. The data support that the MDP is a sustainable diet pattern that could be recommended as a maintenance diet and adjunctive therapy for UC patients in clinical remission. ClinicalTrials.gov no: NCT0305371.
Topics: Adult; Humans; Female; Middle Aged; Male; Colitis, Ulcerative; Diet, Mediterranean; Prospective Studies; RNA, Ribosomal, 16S; Canada; Inflammation; Feces; Butyric Acid; Leukocyte L1 Antigen Complex
PubMed: 37095601
DOI: 10.1093/ecco-jcc/jjad073 -
Frontiers in Immunology 2023Several existing studies have revealed that the occurrence of lichen planus (LP) is relevant to the gut microbiota, and the causal relationship between gut microbiota...
PURPOSE
Several existing studies have revealed that the occurrence of lichen planus (LP) is relevant to the gut microbiota, and the causal relationship between gut microbiota and LP was analyzed using the Mendelian randomization (MR) method.
METHODS
Through the two-sample MR method, single nucleotide polymorphisms (SNPs) relevant to gut microbiota were selected as instrument variables (IVs) to evaluate the causal association between gut microbiota and the risk of LP.
RESULTS
According to the selection criteria of inverse-variance weighted (IVW), six bacterial genera were found to be significantly linked to the initiation of LP; The IVW results suggested that Oxalobacteraceae, Victivallaceae, and Actinobacteria could restrain the initiation of LP, showing protective effects against LP. Desulfovibrio, Veillonella, and Ruminococcus gauvreauii groups were demonstrated to have casual correlations with the onset of LP.
CONCLUSION
The relationship between gut microbiota and LP was not a single positive or inverse relationship. Investigation of the causal relationship of these gut microbiota with LP could further provide evidence for the intestine-skin axis theory. However, the specific mechanism of microorganisms affecting the skin remains to be clarified. In this paper, the protective effects and mechanisms of Oxalobacteraceae, Victivallaceae, and Actinobacteria on LP require further exploration.
PubMed: 37767099
DOI: 10.3389/fimmu.2023.1235982 -
Nutrients Sep 2023Several observational studies and clinical trials have shown that the gut microbiota is associated with urological cancers. However, the causal relationship between gut...
BACKGROUND
Several observational studies and clinical trials have shown that the gut microbiota is associated with urological cancers. However, the causal relationship between gut microbiota and urological cancers remains to be elucidated due to many confounding factors.
METHODS
In this study, we used two thresholds to identify gut microbiota GWAS from the MiBioGen consortium and obtained data for five urological cancers from the UK biobank and Finngen consortium, respectively. We then performed a two-sample Mendelian randomization (MR) analysis with Wald ratio or inverse variance weighted as the main method. We also performed comprehensive sensitivity analyses to verify the robustness of the results. In addition, we performed a reverse MR analysis to examine the direction of causality.
RESULTS
Our study found that family , genus , genus , genus , genus , genus , genus , and genus were related to bladder cancer; genus , genus , genus , genus , and genus were related to prostate cancer; class , class , family , genus , genus , genus , genus , genus , and genus were related to renal cell cancer; family , family , genus , genus , and genus were related to renal pelvis cancer; family , genus , and genus were related to testicular cancer. Comprehensive sensitivity analyses proved that our results were reliable.
CONCLUSIONS
Our study confirms the role of specific gut microbial taxa on urological cancers, explores the mechanism of gut microbiota on urological cancers from a macroscopic level, provides potential targets for the screening and treatment of urological cancers, and is dedicated to providing new ideas for clinical research.
Topics: Male; Humans; Gastrointestinal Microbiome; Testicular Neoplasms; Mendelian Randomization Analysis; Urologic Neoplasms; Kidney Neoplasms; Clostridiaceae; Lactobacillales; Bacteroidetes; Genome-Wide Association Study
PubMed: 37764869
DOI: 10.3390/nu15184086 -
Journal of Cancer 2024Regulating the immune system is a crucial measure of gut microbiota (GM) that influences the development of diseases. The causal role of GM on Non-small cell lung...
Regulating the immune system is a crucial measure of gut microbiota (GM) that influences the development of diseases. The causal role of GM on Non-small cell lung cancer (NSCLC) and whether it can be mediated by immune cells is still unknown. We performed a two-step, two-sample Mendelian randomization study with an Inverse variance weighted (IVW) approach to investigate the causal role of GM on NSCLC and the mediation effect of immune cells between the association of GM and NSCLC. MR analyses determined the protective effects of 6 genera on NSCLC (Bacteroides, Roseburia, Alistipes, Methanobrevibacter, Ruminococcus gauvreauii group, and Peptococcus). In addition, 38 immune cell traits were suggestively associated with NSCLC. Of note, the mediation MR illustrated the causal role of Genus-Peptococcus on NSCLC (Total effect IVW: OR = 0.790, 95% CI [0.657, 0.950], P = 0.012) was to a large proportion mediated by CD45 on HLA DR CD4 in TBNK panel (-034 (95% CI [-0.070, -0.005]; P = 0.037), accounting for 14.4% of Total effect). The study suggested a causal relationship between GM and NSCLC, which may be mediated by immune cells.
PubMed: 38434967
DOI: 10.7150/jca.92699 -
Frontiers in Microbiology 2023Despite the growing body of evidence, the link between the gut microbiota and different types of tumors, such as colorectal, gastric, and liver cancer, is becoming more...
INTRODUCTION
Despite the growing body of evidence, the link between the gut microbiota and different types of tumors, such as colorectal, gastric, and liver cancer, is becoming more apparent. The gut microbiota can be used as a reference for evaluating various diseases, including cancer, and can also act as risk factors or preventive factors. However, the specific connection between the gut microbiota and the advancement of esophageal cancer has yet to be investigated. Therefore, the aim of this research is to clarify the possible causal influence of intestinal microorganisms on the vulnerability to esophageal cancer through the utilization of Mendelian randomization (MR) studies.
METHODS
In this study, we employed a two-sample Mendelian randomization approach to evaluate the unbiased causal association between 150 different gut microbiota types and the occurrence of esophageal cancer. Following the selection from the IEU GWAS database and SNP filtration, we utilized various MR statistical techniques on the suitable instrumental variables. These included IVW methods, employing inverse variance weighting. Additionally, we performed a range of sensitivity analyses to confirm the heterogeneity and pleiotropy of the instrumental variables, thus ensuring the reliability of the outcomes.
RESULTS
The increased likelihood of developing esophageal cancer is linked to the genetically predicted high levels of , and . Conversely, a decreased risk of esophageal cancer is associated with the high abundance of , and . No heterogeneity and pleiotropy were detected in the sensitivity analysis.
DISCUSSION
We found that 11 types of gut microbial communities are associated with esophageal cancer, thereby confirming that the gut microbiota plays a significant role in the path.
PubMed: 38107856
DOI: 10.3389/fmicb.2023.1286598 -
Nutrients Jul 2023The gut microbiota is a dynamic community of bacteria distributed in the gastroenteric tract and changes in response to diseases, diet, use of antibiotics and... (Review)
Review
The gut microbiota is a dynamic community of bacteria distributed in the gastroenteric tract and changes in response to diseases, diet, use of antibiotics and probiotics, hygiene status, and other environmental factors. Dysbiosis, a disruption of the normal crosstalk between the host and the microbes, is associated with obesity, diabetes, cancer, and cardiovascular diseases, is linked to a reduction of anti-inflammatory bacteria like and , and to an increase in the growth of proinflammatory species like and . Some plants possess anticancer properties and various studies have reported that some of these are also able to modulate the gut microbiota. The aim of this work is to evaluate the crucial relationship between medical plants and gut microbiota and the consequences on the onset and progression of cancer. In vivo studies about hematological malignancies showed that beta-glucans tie to endogenous antibeta glucan antibodies and to iC3b, an opsonic fragment of the central complement protein C3, leading to phagocytosis of antibody-targeted neoplastic cells and potentiation of the cytotoxic activity of the innate immune system if administered together with monoclonal antibodies. In conclusion, this review suggests the potential use of medical plants to improve gut dysbiosis and assist in the treatment of cancer.
Topics: Humans; Gastrointestinal Microbiome; Dysbiosis; Obesity; Bacteria; Diet; Neoplasms; Probiotics
PubMed: 37571264
DOI: 10.3390/nu15153327 -
BMC Microbiology Nov 2023Infantile cholestasis (IC) is the most common hepatobiliary disease in infants, resulting in elevated direct bilirubin levels. Indeed, hepatointestinal circulation...
BACKGROUND
Infantile cholestasis (IC) is the most common hepatobiliary disease in infants, resulting in elevated direct bilirubin levels. Indeed, hepatointestinal circulation impacts bile acid and bilirubin metabolism. This study evaluates changes in the gut microbiota composition in children with IC and identifies abnormal metabolite profiles associated with microbial alterations.
RESULTS
The gut microbiota in the IC group exhibits the higher abundance of Veillonella, Streptococcus and Clostridium spp. (P < 0.05), compared to healthy infants (CON) group. Moreover, the abundance of Ruminococcus, Vibrio butyricum, Eubacterium coprostanogenes group, Intestinibacter, and Faecalibacterium were lower (P < 0.05). In terms of microbiota-derived metabolites, the levels of fatty acids (palmitoleic, α-linolenic, arachidonic, and linoleic) (P < 0.05) increased and the levels of amino acids decreased in IC group. Furthermore, the abundances of Ruminococcus, Eubacterium coprostanoligenes group, Intestinibacter and Butyrivibrio are positively correlated with proline, asparagine and aspartic acid, but negatively correlated with the α-linolenic acid, linoleic acid, palmitoleic acid and arachidonic acid. For analysis of the relationship between the microbiota and clinical index, it was found that the abundance of Veillonella and Streptococcus was positively correlated with serum bile acid content (P < 0.05), while APTT, PT and INR were negatively correlated with Faecalibalum and Ruminococcus (P < 0.05).
CONCLUSION
Microbiota dysbiosis happened in IC children, which also can lead to the abnormal metabolism, thus obstructing the absorption of enteral nutrition and aggravating liver cell damage. Veillonella, Ruminococcus and Butyrivibrio may be important microbiome related with IC and need further research.
Topics: Infant; Child; Humans; Gastrointestinal Microbiome; Cholestasis; Liver; Streptococcus; Bilirubin; Bile Acids and Salts
PubMed: 37980506
DOI: 10.1186/s12866-023-03115-1 -
Neurology International Jul 2023Fibromyalgia is a widespread chronic condition characterized by pain and fatigue. Among the long list of physiological disturbances linked to this syndrome,...
Fibromyalgia is a widespread chronic condition characterized by pain and fatigue. Among the long list of physiological disturbances linked to this syndrome, mitochondrial imbalance and oxidative stress stand out. Recently, the crosstalk between mitochondria and intestinal microbiota has caught the attention of biomedical researchers, who have found connections between this axis and several inflammatory and pain-related conditions. Hence, this pilot descriptive study focused on characterizing the mitochondrial mass/mitophagy ratio and total antioxidant capacity in PBMCs, as well as some microbiota components in feces, from a Peruvian cohort of 19 females and 7 males with FM. Through Western blotting, electrochemical oxidation, ELISA, and real-time qPCR, we determined VDAC1 and MALPLC3B protein levels; total antioxidant capacity; secretory immunoglobulin A (sIgA) levels; and , and ratios; as well as spp., spp., and levels, respectively. We found statistically significant differences in spp. and spp. levels between females and males, as well as a marked polarization in mitochondrial mass in both groups. Taken together, our results point to a mitochondrial imbalance in FM patients, as well as a sex-dependent difference in intestinal microbiota composition.
PubMed: 37489361
DOI: 10.3390/neurolint15030055 -
Renal Failure Dec 2023Vascular calcification (VC) is an independent risk factor for cardiovascular mortality in end-stage renal disease (ESRD) patients. The pathogenesis of VC is complicated...
INTRODUCTION
Vascular calcification (VC) is an independent risk factor for cardiovascular mortality in end-stage renal disease (ESRD) patients. The pathogenesis of VC is complicated and unclear. Uremic toxins produced by gut microbiota can promote VC. This study aims to identify the differences in gut microbiota between the different VC groups and the main bacteria associated with VC in hemodialysis (HD) patients in an attempt to open up new preventive and therapeutic approaches and define the probable mechanism for VC in HD patients in the future.
METHODS
A total of 73 maintenance HD patients were enrolled in this cross-sectional study. According to the abdominal aortic calcification (AAC) scores, the participants were divided into the high AAC score group and the low AAC score group. High-throughput sequencing of the gut microbiota was performed and the results were evaluated by alpha diversity, beta diversity, species correlation, and model predictive analyses.
RESULTS
The prevalence of VC was 54.79% (40/73) in the study. The majority of phyla in the two groups were the same, including , , , and . The microbial diversity in the high AAC score group had a decreasing trend ( = 0.050), and the species abundance was significantly lower ( = 0.044) than that in the low AAC score group. The HD patients with high AAC scores showed an increased abundance of and decreased abundances of and at the phylum level; increased abundances of and and decreased abundances of and at the genus level (0.05). and were positively correlated with VC, and , and were negatively correlated with VC. had the greatest influence on VC in HD patients, followed by and
CONCLUSIONS
Our results provide clinical evidence that there was a difference in gut microbiota between the different VC groups in HD patients. a lipopolysaccharide (LPS)-producing bacterium, was positively correlated with VC and had the greatest influence on VC. a short-chain fatty acid (SCFA)-producing bacterium, was negatively correlated with VC and had the second strongest influence on VC in HD patients. The underlying mechanism is worth studying. These findings hint at a new therapeutic target.
Topics: Humans; Gastrointestinal Microbiome; Cross-Sectional Studies; Renal Dialysis; Kidney Failure, Chronic; Vascular Calcification; Bacteria
PubMed: 36632746
DOI: 10.1080/0886022X.2022.2148538