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Frontiers in Endocrinology 2023There is some evidence for an association between gut microbiota and nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), and viral hepatitis, but no...
OBJECTIVE
There is some evidence for an association between gut microbiota and nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), and viral hepatitis, but no studies have explored their causal relationship.
METHODS
Instrumental variables of the gut microbiota (N = 13266) and gut microbiota-derived metabolites (N = 7824) were acquired, and a Mendelian randomization study was performed to explore their influence on NAFLD (1483 European cases and 17,781 European controls), ALD (2513 European cases and 332,951 European controls), and viral hepatitis risk (1971 European cases and 340,528 European controls). The main method for examining causality is inverse variance weighting (IVW).
RESULTS
IVW results confirmed that ( = 0.0249), ( = 0.0237), ( = 0.0245), ( = 0.0083), ( = 0.0163), and ( = 0.0472) were protective factors for NAFLD, and ( = 0.0120) was detrimental for NAFLD. The higher abundance of three genera, ( = 0.0388), ( = 0.0252), and ( = 0.0364), was correlated with a lower risk of ALD, while level was associated with a higher risk of ALD ( = 0.0371). The ( = 0.0069) and ( = 0.0195) were related to a higher risk of viral hepatitis. Besides, alanine ( = 0.0076) and phenyllactate ( = 0.0100) were found to be negatively correlated with NAFLD, while stachydrine (O = 0.0244) was found to be positively associated with NAFLD. The phenylacetate ( = 0.0353) and ursodeoxycholate ( = 0.0144) had a protective effect on ALD, while the threonate ( = 0.0370) exerted a detrimental influence on ALD. The IVW estimates of alanine ( = 0.0408) and cholate ( = 0.0293) showed their suggestive harmful effects against viral hepatitis, while threonate ( = 0.0401) displayed its suggestive protective effect against viral hepatitis.
CONCLUSION
In conclusion, our research supported causal links between the gut microbiome and its metabolites and NAFLD, ALD, and viral hepatitis.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Alanine; Clostridiales
PubMed: 37476494
DOI: 10.3389/fendo.2023.1159148 -
Nutrition Journal Jul 2023Resistance training adaptively increases muscle strength and mass, contributing to athletic performance and health promotion. Dietary intervention with natural foods... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Resistance training adaptively increases muscle strength and mass, contributing to athletic performance and health promotion. Dietary intervention with natural foods provides nutrients that help accelerate muscle adaptation to training. Matcha green tea contains several bioactive factors such as antioxidants, amino acids, and dietary fibers; however, its effect on muscle adaptation is unclear. In this study, we aimed to investigate the effects of matcha beverage intake on muscle adaptation to resistance training.
METHODS
Healthy, untrained men were randomized into placebo and matcha groups. Participants consumed either a matcha beverage containing 1.5 g of matcha green tea powder or a placebo beverage twice a day and engaged in resistance training programs for 8 (trial 1) or 12 weeks (trial 2).
RESULTS
In trial 1, maximum leg strength after training tended to increase more in the matcha group than that in the placebo group. In the matcha group, subjective fatigue after exercise at 1 week of training was lower than that in the placebo group. Gut microbe analysis showed that the abundance of five genera changed after matcha intake. The change in Ruminococcus, Butyricimonas, and Oscillospira compositions positively correlated with the change in maximum strength. In trial 2, the change in skeletal muscle mass in response to training was larger in the matcha group. In addition, the salivary cortisol level was lower in the matcha group than that in the placebo group.
CONCLUSION
Daily intake of matcha green tea beverages may help in muscle adaptation to training, with modulations in stress and fatigue responses and microbiota composition.
Topics: Male; Humans; Antioxidants; Resistance Training; Tea; Muscle Strength; Exercise; Muscle, Skeletal
PubMed: 37403052
DOI: 10.1186/s12937-023-00859-4 -
Gut Microbes Dec 2023Numerous studies have described the notable impact of gut microbiota on the brain in Alzheimer's disease (AD) via the gut - brain axis. However, the molecular mechanisms...
Numerous studies have described the notable impact of gut microbiota on the brain in Alzheimer's disease (AD) via the gut - brain axis. However, the molecular mechanisms underlying the involvement of gut microbiota in the development of AD are limited. This study aimed to explore the potential mechanisms of gut microbiota in AD by integrating multi-omics data. In this study, APP/PS1 and WT mice at nine months of age were used as study mouse model. Cognitive function was assessed using the Morris water maze test. The levels of Aβ plaque and neuroinflammation in the brain were detected using immunofluorescence and PET/CT. In addition, we not only used 16S rRNA gene sequencing and metabolomics to explore the variation characteristics of gut microbiota and serum metabolism abundance, but also combined spatial metabolomics and transcriptomics to explore the change in the brain and identify their potential correlation. APP/PS1 mice showed significant cognitive impairment and amyloid-β deposits in the brain. The abundance of gut microbiota was significantly changed in APP/PS1 mice, including decreased , , , and and increased . The integration of serum untargeted metabolomics and brain spatial metabolomics showed that glycerophospholipid metabolism was a common alteration pathway in APP/PS1 mice. Significant proliferation and activation of astrocyte and microglia were observed in APP/PS1 mice, accompanied by alterations in immune pathways. Integration analysis and fecal microbiota transplantation (FMT) intervention revealed potential association of gut microbiota, host glycerophospholipid metabolism, and neuroinflammation levels in APP/PS1 mice.
Topics: Mice; Animals; Amyloid beta-Protein Precursor; Mice, Transgenic; Neuroinflammatory Diseases; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Multiomics; Positron Emission Tomography Computed Tomography; Alzheimer Disease; Glycerophospholipids; Disease Models, Animal
PubMed: 37992400
DOI: 10.1080/19490976.2023.2282790 -
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 -
Frontiers in Endocrinology 2023Observation studies have confirmed the association between the gut microbiome and reproductive endocrine diseases (REDs), namely, polycystic ovary syndrome (PCOS),...
BACKGROUND
Observation studies have confirmed the association between the gut microbiome and reproductive endocrine diseases (REDs), namely, polycystic ovary syndrome (PCOS), endometriosis, and female infertility. However, their association has never been confirmed by a two-sample Mendelian randomization (MR) analysis.
METHODS
We conducted a two-sample MR analysis to evaluate the relationship between the gut microbiome and the three aforementioned REDs. In order to get more comprehensive results, two different thresholds were adopted to select instrumental variables (IVs): one was a locus-wide significance threshold (1.0×10) and the other was a genome-wide significance level (< 5×10). Summary-level statistics for the gut microbiome and REDs were collected from public databases. Inverse-variance weighted (IVW) was the main method used to estimate causality, and sensitivity analyses were conducted to validate the MR results.
RESULTS
At the locus-wide significance level, we identified that the genera Streptococcus (OR=1.52, 95%CI: 1.13-2.06, =0.006) and RuminococcaceaeUCG005 (OR=1.39, 95%CI: 1.04-1.86, =0.028) were associated with a high risk of PCOS, while Sellimonas (OR= 0.69, 95%CI: 0.58-0.83, =0.0001) and RuminococcaceaeUCG011(OR=0.76, 95%CI: 0.60-0.95, =0.017) were linked to a low PCOS risk. The genus Coprococcus2 (OR=1.20, 95%CI: 1.01-1.43, =0.039) was correlated with an increased risk of female infertility, while Ruminococcus torques (OR=0.69, 95%CI: 0.54-0.88, =0.002) were negatively associated with the risk of female infertility. The genera Olsenella (OR= 1.11, 95%CI: 1.01-1.22, =0.036), Anaerotruncus (OR= 1.25, 95%CI: 1.03-1.53, =0.025), and Oscillospira (OR= 1.21, 95%CI: 1.01-1.46, =0.035) were linked to a high risk of endometriosis. However, the results showed that the gut microbiome did not possess a causal link with REDs risk based on the genome-wide significance level. Sensitivity analyses further confirmed the robustness of the MR results.
CONCLUSION
Our study provides evidence that gut microbiome is closely related with REDs. Subsequent studies should be conducted to promote microbiome-orientated therapeutic strategies for managing REDs.
Topics: Female; Humans; Gastrointestinal Microbiome; Endometriosis; Infertility, Female; Mendelian Randomization Analysis; Polycystic Ovary Syndrome
PubMed: 37600687
DOI: 10.3389/fendo.2023.1164186 -
Frontiers in Immunology 2023COVID-19 could develop severe respiratory symptoms in certain infected patients, especially in the patients with immune disorders. Gut microbiome and plasma metabolome...
BACKGROUND
COVID-19 could develop severe respiratory symptoms in certain infected patients, especially in the patients with immune disorders. Gut microbiome and plasma metabolome act important immunological modulators in the human body and could contribute to the immune responses impacting the progression of COVID-19. However, the causal relationship between specific intestinal bacteria, metabolites and severe COVID-19 remains not clear.
METHODS
Based on two-sample Mendelian randomization (MR) framework, the causal effects of 131 intestinal taxa and 452 plasma metabolites on severe COVID-19 were evaluated. Single nucleotide polymorphisms (SNPs) strongly associated with the abundance of intestinal taxa and the concentration of plasma metabolites had been utilized as the instrument variables to infer whether they were causal factors of severe COVID-19. In addition, mediation analysis was conducted to find the potential association between the taxon and metabolite, and further colocalization analysis had been performed to validate the causal relationships.
RESULTS
MR analysis identified 13 taxa and 53 metabolites, which were significantly associated with severe COVID-19 as causal factors. Mediation analysis revealed 11 mediated relationships. Myo-inositol, 2-stearoylglycerophosphocholine, and alpha-glutamyltyrosine, potentially contributed to the association of and with severe COVID-19, respectively. and could mediate the association of myo-inositol and N-acetylalanine, respectively. In addition, abundance was colocalized with severe COVID-19 (PP.H4 = 0.77) and the colon expression of permeability related protein RASIP1 (PP.H4 = 0.95).
CONCLUSIONS
Our study highlights the potential causal relationships between gut microbiome, plasma metabolome and severe COVID-19, which potentially serve as clinical biomarkers for risk stratification and prognostication and benefit the mechanism mechanistic investigation of severe COVID-19.
Topics: Humans; Gastrointestinal Microbiome; COVID-19; Mendelian Randomization Analysis; Mediation Analysis; Metabolome
PubMed: 37662924
DOI: 10.3389/fimmu.2023.1211612 -
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 -
Cell Host & Microbe Dec 2023Exclusive enteral nutrition (EEN) with fiber-free diets is an effective steroid-sparing treatment to induce clinical remission in children with Crohn's disease (CD)....
Exclusive enteral nutrition (EEN) with fiber-free diets is an effective steroid-sparing treatment to induce clinical remission in children with Crohn's disease (CD). However, the mechanism underlying the beneficial effects of EEN remains obscure. Using a model of microbiota-dependent colitis with the hallmarks of CD, we find that the administration of a fiber-free diet prevents the development of colitis and inhibits intestinal inflammation in colitic animals. Remarkably, fiber-free diet alters the intestinal localization of Mucispirillum schaedleri, a mucus-dwelling pathobiont, which is required for triggering disease. Mechanistically, the absence of dietary fiber reduces nutrient availability and impairs the dissimilatory nitrate reduction to ammonia (DNRA) metabolic pathway of Mucispirillum, leading to its exclusion from the mucus layer and disease remission. Thus, appropriate localization of the specific pathobiont in the mucus layer is critical for disease development, which is disrupted by fiber exclusion. These results suggest strategies to treat CD by targeting the intestinal niche and metabolism of disease-causing microbes.
Topics: Humans; Child; Animals; Crohn Disease; Diet; Colitis; Treatment Outcome; Microbiota
PubMed: 37967555
DOI: 10.1016/j.chom.2023.10.016 -
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