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Nutrients Jun 2021Glucosamine (GLU) is a natural compound found in cartilage, and supplementation with glucosamine has been shown to improve joint heath and has been linked to reduced... (Randomized Controlled Trial)
Randomized Controlled Trial
Glucosamine (GLU) is a natural compound found in cartilage, and supplementation with glucosamine has been shown to improve joint heath and has been linked to reduced mortality rates. GLU is poorly absorbed and may exhibit functional properties in the gut. The purpose of this study was to examine the impact of glucosamine on gastrointestinal function as well as changes in fecal microbiota and metabolome. Healthy males ( = 6) and females ( = 5) (33.4 ± 7.7 years, 174.1 ± 12.0 cm, 76.5 ± 12.9 kg, 25.2 ± 3.1 kg/m, = 11) completed two supplementation protocols that each spanned three weeks separated by a washout period that lasted two weeks. In a randomized, double-blind, placebo-controlled, crossover fashion, participants ingested a daily dose of GLU hydrochloride (3000 mg GlucosaGreen, TSI Group Ltd., Missoula, MT, USA) or maltodextrin placebo. Study participants completed bowel habit and gastrointestinal symptoms questionnaires in addition to providing a stool sample that was analyzed for fecal microbiota and metabolome at baseline and after the completion of each supplementation period. GLU significantly reduced stomach bloating and showed a trend towards reducing constipation and hard stools. Phylogenetic diversity (Faith's PD) and proportions of , , and were significantly reduced following GLU consumption. GLU supplementation significantly reduced individual, total branched-chain, and total amino acid excretion, with no glucosamine being detected in any of the fecal samples. GLU had no effect on fecal short-chain fatty acids levels. GLU supplementation provided functional gut health benefits and induced fecal microbiota and metabolome changes.
Topics: Adult; Cross-Over Studies; Defecation; Dietary Supplements; Double-Blind Method; Feces; Female; Gastrointestinal Microbiome; Gastrointestinal Tract; Glucosamine; Healthy Volunteers; Humans; Male; Phylogeny; Pilot Projects; Polysaccharides
PubMed: 34202877
DOI: 10.3390/nu13072180 -
Frontiers in Immunology 2023Myasthenia gravis (MG) is an autoimmune disease observed to have connections with gut microbiome. We aimed to systematically assess the causal relationships between gut...
BACKGROUND
Myasthenia gravis (MG) is an autoimmune disease observed to have connections with gut microbiome. We aimed to systematically assess the causal relationships between gut microbiome, gut microbiome-derived metabolites, and MG using Mendelian randomization (MR) approach.
METHODS
Summary-level genetic datasets from large-scale genome-wide association studies regarding 196 gut microbial taxa from the MiBioGen consortium (n=18,340), 72 derived metabolites from the TwinsUK and KORA studies (n=7,824), and antiacetylcholine receptor (AChR) antibody-positive MG (case=1,873, control=36,370) were employed for MR causal estimates. The inverse-variance weighted (IVW) method was utilized as the main analysis with MR-Egger, maximum likelihood, simple mode, and weighted median as complements. The tests of Cochran's Q, MR-Egger intercept, Steiger, MR-PRESSO and leave-one-out were implemented for sensitivity analyses.
RESULTS
The forward MR estimates of IVW revealed significant causal associations of the abundance of phylum Actinobacteria, class Gammaproteobacteria, family Defluviitaleac, family Family XIII, and family Peptococcaceae with a reduced risk of MG. Conversely, the abundance of phylum Lentisphaerae, order Mollicutes RF9, order Victivallales, and genus Faecalibacterium was causally associated with an increased risk of MG. The reversed MR analysis proved negative causal correlations between the MG and the abundance of family Peptostreptococcaceae, genus Romboutsia, and genus Subdoligranulum. Regarding the derived metabolites, the IVW estimates revealed that elevated levels of beta-hydroxyisovalerate and methionine were causally associated with a decreased risk of MG, while increased levels of choline and kynurenine were linked to an increased risk of MG. Furthermore, genetically predicted MG was associated with a decreased level of cholesterol. The results obtained from complementary MR methods were similar. These findings remained robust in all sensitivity analyses.
CONCLUSION
Our MR findings support the causal effects of specific gut microbiome taxa and derived metabolites on AChR antibody-positive MG, and vice versa, yielding novel insights into prevention and therapy targets of MG. Future studies may be warranted for validation and pursuing the precise mechanisms.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Myasthenia Gravis; Autoantibodies
PubMed: 38179043
DOI: 10.3389/fimmu.2023.1279845 -
Frontiers in Microbiology 2023Numerous studies have revealed associations between gut microbiota and adipose tissue. However, the specific functional bacterial taxa and their causal relationships...
BACKGROUND
Numerous studies have revealed associations between gut microbiota and adipose tissue. However, the specific functional bacterial taxa and their causal relationships with adipose tissue production in different regions of the body remain unclear.
METHODS
We conducted a bidirectional two-sample Mendelian Randomization (MR) study using aggregated data from genome-wide association studies (GWAS) for gut microbiota and adipose tissue. We employed methods such as inverse variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode to assess the causal relationships between gut microbiota and subcutaneous adipose tissue (SAT) as well as visceral adipose tissue (VAT). Cochran's Q test, MR-Egger regression intercept analysis, and MR-PRESSO were used to test for heterogeneity, pleiotropy, and outliers of the instrumental variables, respectively. Reverse MR was employed to evaluate the reverse causal relationships between SAT, VAT, and gut microbiota with significant associations.
RESULTS
IVW results demonstrated that were protective factors for SAT production (OR = 0.88, 95% CI: 0.80-0.96, = 0.005) and VAT production (OR = 0.91, 95% CI: 0.83-0.99, = 0.030). Various bacterial taxa including (OR = 0.94, 95% CI: 0.89-0.99, = 0.017), (OR = 0.96, 95% CI: 0.92-1.00, = 0.029), and (OR = 0.90, 95% CI: 0.83-0.98, = 0.012) were associated only with decreased SAT production. (OR = 1.05, 95% CI: 1.02-1.10, = 0.005), (OR = 1.08, 95% CI: 1.01-1.15, = 0.028), (OR = 1.08, 95% CI: 1.01-1.17, = 0.034), and (OR = 1.05, 95% CI: 1.00-1.10, = 0.047) were risk factors for SAT production. Meanwhile, (OR = 0.95, 95% CI: 0.91-0.99, = 0.019), (OR = 0.93, 95% CI: 0.88-0.99, = 0.022), and Defluviitaleaceae UCG011 (OR = 0.94, 95% CI: 0.89-0.99, = 0.024) were protective factors for VAT production. Furthermore, (OR = 1.09, 95% CI: 1.01-1.17, = 0.018), (OR = 1.09, 95% CI: 1.01-1.19, = 0.037), Alloprevotella (OR = 1.05, 95% CI: 1.00-1.10, = 0.038), and (OR = 1.07, 95% CI: 1.00-1.15, = 0.042) were associated with VAT accumulation. Additionally, reverse MR revealed significant associations between SAT, VAT, and (IVW: OR = 1.57, 95% CI: 1.18-2.09, = 0.002) as well as (IVW: OR = 1.14, 95% CI: 1.01-1.29, = 0.029), both acting as risk factors. Sensitivity analyzes during bidirectional MR did not identify heterogeneity or pleiotropy.
CONCLUSION
This study unveils complex causal relationships between gut microbiota and SAT/VAT, providing novel insights into the diagnostic and therapeutic potential of gut microbiota in obesity and related metabolic disorders.
PubMed: 38029216
DOI: 10.3389/fmicb.2023.1285982 -
Experimental Dermatology Jan 2018Rosacea is a chronic inflammatory dermatosis affecting the face and eyes. An association between systemic comorbidities and rosacea has been reported, but the link to...
Rosacea is a chronic inflammatory dermatosis affecting the face and eyes. An association between systemic comorbidities and rosacea has been reported, but the link to enteral microbiota is uncertain. We aimed to investigate the link between rosacea and enteral microbiota. A cross-sectional study was performed in a sample of Korean women who participated in a health check-up programme at the Kangbuk Samsung Hospital Health Screening Center between 23 June 2014 and 5 September 2014. The gut microbiome was evaluated by 16S rRNA gene and metagenome sequence analyses. A total of 12 rosacea patients and 251 controls were enrolled. We identified links between rosacea and several changes in gut microbiota: reduced abundance of Peptococcaceae family unknown genus, Methanobrevibacter (genus), Slackia (genus), Coprobacillus (genus), Citrobacter (genus), and Desulfovibrio (genus), and increased abundance of Acidaminococcus (genus), Megasphaera (genus), and Lactobacillales order unknown family unknown genus. A link between rosacea and enteral microbiota was observed in this metagenomic study. A large and elaborate study is needed to confirm these findings and to elucidate the mechanisms involved.
Topics: Acidaminococcus; Adult; Case-Control Studies; Citrobacter; Cross-Sectional Studies; Desulfovibrio; Female; Gastrointestinal Microbiome; Humans; Inflammation; Megasphaera; Metagenome; Methanobrevibacter; Middle Aged; Peptococcaceae; RNA, Ribosomal, 16S; Republic of Korea; Rosacea; Skin Diseases
PubMed: 28636759
DOI: 10.1111/exd.13398 -
World Journal of Hepatology Jun 2022Gut dysbiosis and changes in body composition (, a decrease in the proportion of muscle mass and an increase in extracellular fluid) are common in cirrhosis.
BACKGROUND
Gut dysbiosis and changes in body composition (, a decrease in the proportion of muscle mass and an increase in extracellular fluid) are common in cirrhosis.
AIM
To study the relationship between the gut microbiota and body composition in cirrhosis.
METHODS
This observational study included 46 patients with cirrhosis. Stool microbiome was assessed using 16S rRNA gene sequencing. Multifrequency bioelectrical impedance analysis was performed to assess body composition in these patients.
RESULTS
An increase in fat mass and a decrease in body cell mass were noted in 23/46 (50.0%) and 15/46 (32.6%) patients, respectively. Changes in the gut microbiome were not independently associated with the fat mass percentage in cirrhosis. The abundance of ( = 0.041) and ( = 0.001) increased, whereas that of ( = 0.006), ( = 0.021), ( = 0.033), ( = 0.043), ( = 0.028), and ( = 0.015) decreased in the gut microbiome of patients with body cell mass deficiency. The amount of extracellular fluid increased in 22/46 (47.6%) patients. Proteobacteria abundance ( < 0.001) increased, whereas Firmicutes ( = 0.023), Actinobacteria ( = 0.026), Bacilli ( = 0.008), ( = 0.027), ( = 0.038), ( = 0.047), ( = 0.015), ( = 0.003), ( = 0.024), ( = 0.002), ( = 0.030), ( = 0.040), ( = 0.023), ( = 0.008), and ( = 0.024) abundance decreased in these patients. Patients with clinically significant ascites ( = 9) had a higher abundance of Proteobacteria ( = 0.031) and a lower abundance of Actinobacteria ( = 0.019) and Bacteroidetes ( = 0.046) than patients without clinically significant ascites ( = 37).
CONCLUSION
Changes in the amount of body cell mass and extracellular fluid are associated with changes in the gut microbiome in cirrhosis patients.
PubMed: 35978666
DOI: 10.4254/wjh.v14.i6.1210 -
Journal of Applied Microbiology Apr 2022How benzene is metabolized by microbes under anoxic conditions is not fully understood. Here, we studied the degradation pathways in a benzene-mineralizing,...
AIMS
How benzene is metabolized by microbes under anoxic conditions is not fully understood. Here, we studied the degradation pathways in a benzene-mineralizing, nitrate-reducing enrichment culture.
METHODS AND RESULTS
Benzene mineralization was dependent on the presence of nitrate and correlated to the enrichment of a Peptococcaceae phylotype only distantly related to known anaerobic benzene degraders of this family. Its relative abundance decreased after benzene mineralization had terminated, while other abundant taxa-Ignavibacteriaceae, Rhodanobacteraceae and Brocadiaceae-slightly increased. Generally, the microbial community remained diverse despite the amendment of benzene as single organic carbon source, suggesting complex trophic interactions between different functional groups. A subunit of the putative anaerobic benzene carboxylase previously detected in Peptococcaceae was identified by metaproteomic analysis suggesting that benzene was activated by carboxylation. Detection of proteins involved in anaerobic ammonium oxidation (anammox) indicates that benzene mineralization was accompanied by anammox, facilitated by nitrite accumulation and the presence of ammonium in the growth medium.
CONCLUSIONS
The results suggest that benzene was activated by carboxylation and further assimilated by a novel Peptococcaceae phylotype.
SIGNIFICANCE AND IMPACT OF THE STUDY
The results confirm the hypothesis that Peptococcaceae are important anaerobic benzene degraders.
Topics: Anaerobiosis; Benzene; Microbiota; Nitrates; Oxidation-Reduction; Peptococcaceae
PubMed: 34995421
DOI: 10.1111/jam.15443 -
BMC Neurology Jan 2024Myasthenia gravis (MG) is an autoimmune disease that affects neuromuscular junction. The literature suggests the involvement of circulating cytokines (CK), gut...
BACKGROUND
Myasthenia gravis (MG) is an autoimmune disease that affects neuromuscular junction. The literature suggests the involvement of circulating cytokines (CK), gut microbiota (GM), and serum metabolites (SM) with MG. However, this research is limited to observational trials, and comprehensive causal relationship studies have not been conducted. Based on published datasets, this investigation employed Mendelian Randomization (MR) to analyze the known and suspected risk factors and biomarkers causal association of MG and its subtypes.
METHODS
This research used two-sample MR and linkage disequilibrium score (LDSC) regression of multiple datasets to aggregate datasets acquired from the genome-wide association studies (GWAS) to assess the association of MG with 41-CK, 221-GM, and 486-SM. For sensitivity analysis and to validate the robustness of the acquired data, six methods were utilized, including MR-Egger regression, inverse variance weighting (IVW), weighted median, and MR-PRESSO.
RESULTS
The MR method identified 20 factors significantly associated with MG, including 2 CKs, 6 GMs, and 9 SMs. Further analysis of the factors related to the two MG subtypes, early-onset MG (EOMG) and late-onset MG (LOMG), showed that EOMG had a high overlap with MG in the intestinal flora, while LOMG had a greater similarity in CKs and SMs. Furthermore, LDSC regression analysis indicated that Peptococcaceae, oxidized biliverdin, and Kynurenine had significant genetic correlations with general MG, whereas EOMG was highly correlated with Intestinibacter, while LOMG had significant genetic associations with Kynurenine and Glucose.
CONCLUSION
This research furnishes evidence for the potential causal associations of various risk factors with MG and indicates a heterogeneous relationship between CKs, GMs, and SMs with MG subtypes.
Topics: Humans; Genome-Wide Association Study; Kynurenine; Mendelian Randomization Analysis; Myasthenia Gravis; Risk Factors; Biomarkers; Cytokines
PubMed: 38238684
DOI: 10.1186/s12883-024-03529-y -
Genes Feb 2022Polycystic ovary syndrome (PCOS) is a very common endocrine condition in women in India. Gut microbiome alterations were shown to be involved in PCOS, yet it is...
Polycystic ovary syndrome (PCOS) is a very common endocrine condition in women in India. Gut microbiome alterations were shown to be involved in PCOS, yet it is remarkably understudied in Indian women who have a higher incidence of PCOS as compared to other ethnic populations. During the regional PCOS screening program among young women, we recruited 19 drug naive women with PCOS and 20 control women at the Sher-i-Kashmir Institute of Medical Sciences, Kashmir, North India. We profiled the gut microbiome in faecal samples by 16S rRNA sequencing and included 40/58 operational taxonomic units (OTUs) detected in at least 1/3 of the subjects with relative abundance (RA) ≥ 0.1%. We compared the RAs at a family/genus level in PCOS/non-PCOS groups and their correlation with 33 metabolic and hormonal factors, and corrected for multiple testing, while taking the variation in day of menstrual cycle at sample collection, age and BMI into account. Five genera were significantly enriched in PCOS cases: , , and previously reported for PCOS , and confirmed by different statistical models. At the family level, the relative abundance of was enriched, whereas was decreased among cases. We observed increased relative abundance of and with higher fasting blood glucose levels, and and with larger hip, waist circumference, weight, and with lower prolactin levels. We also detected a novel association between and follicle-stimulating hormone levels and between and alkaline phosphatase, independently of the BMI of the participants. Our report supports that there is a relationship between gut microbiome composition and PCOS with links to specific reproductive health metabolic and hormonal predictors in Indian women.
Topics: Bacteroidetes; Bifidobacterium; Feces; Female; Gastrointestinal Microbiome; Humans; Polycystic Ovary Syndrome; RNA, Ribosomal, 16S
PubMed: 35205422
DOI: 10.3390/genes13020379 -
Heliyon Feb 2024Autoimmune thyroiditis (AIT), also known as Hashimoto's thyroiditis (HT) or chronic lymphocytic thyroiditis, is a prevalent autoimmune disorder. Despite its high...
BACKGROUND
Autoimmune thyroiditis (AIT), also known as Hashimoto's thyroiditis (HT) or chronic lymphocytic thyroiditis, is a prevalent autoimmune disorder. Despite its high prevalence, the pathogenesis of AIT remains unclear. Previous studies have suggested a potential association between gut microbiota and AIT. However, whether this relationship is causal or coincidental remains uncertain. To address this gap in knowledge, our study aimed to investigate the potential causal association between gut microbiota and AIT using the two-sample Mendelian randomization (MR) method.
METHODS
Summary-level gut microbiota data comprising 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla) were obtained from the comprehensive MiBioGen study. Genetic associations with 22 gastrointestinal diseases were extracted from the UK Biobank, FinnGen study, and various extensive GWAS studies. A meticulous MR analysis was conducted to evaluate the causal relationship between genetically predicted gut microbiota and these gastrointestinal diseases. Sensitivity analyses and tests for heterogeneity were systematically performed to validate the reliability of our findings.
RESULTS
Six gut microbiota species showed significant associations with AIT according to the IVW method. Among them, the following exhibited negative associations with AIT: family Alcaligenaceae, family Pasteurellaceae (ID: 3689), family Peptococcaceae, genus Lachnospira, genus Victivallis, and order Pasteurellales (ID: 3688). No evidence of pleiotropy or heterogeneity was detected.
CONCLUSION
The MR analysis uncovered a causal relationship at the genetic prediction level between specific gut microbiota and AIT. These findings offer novel insights into the mechanisms governing the development of AIT mediated by gut microbiota. This knowledge could inform the design of future interventions, potentially involving microbiome-related strategies, to address the mechanisms associated with AIT development.
PubMed: 38356548
DOI: 10.1016/j.heliyon.2024.e25652 -
International Immunopharmacology Oct 2023Inflammasome has been reported to play an important role in the pathogenesis and progression of hematologic malignancies. As one of the backbone drugs for treating acute...
BACKGROUND
Inflammasome has been reported to play an important role in the pathogenesis and progression of hematologic malignancies. As one of the backbone drugs for treating acute lymphoblastic leukemia (ALL), the anti-inflammatory effect of mercaptopurine (6-MP) and the impact of gut microbiome changes caused by 6-MP on anti-inflammasome remain unclear.
OBJECTIVE
We aimed to explore the association between 6-MP therapeutic effects and microbiome-involved inflammatory responses in ALL mice models.
STUDY DESIGN
ALL murine model was built by i.v. injecting murine L1210 cells into DBA/2 mice (model group). Two weeks after cell injections, 6-MP was orally administrated for 14 days (6-MP group). Fecal samples of mice were collected at different time points. Cecum short-chain fatty acids (SCFAs) concentrations were determined by LC-MS/MS method. Serum cytokines were measured using a cytometric bead array. Gut microbiota composition in mice was explored using 16S rRNA gene sequencing.
RESULTS
The anti-tumor effect of 6-MP was proved in ALL mice models. The levels of pro-inflammatory factors IL-6 and TNFα significantly decreased after the administration of 6-MP. Cecum contents' acetate, propionate, and butyrate levels were negatively correlated with IL-6 (correlation coefficient: acetate, -0.24; propionate, -0.26; butyrate, -0.17) and TNFα (correlation coefficient: acetate, -0.45; propionate, -0.42; butyrate, -0.31) changes. Relative abundance changes of f_Lachnospiraceae.g_ASF356 and f_Peptococcaceae.g_uncultured were in accordance with the changes of butyrate levels and opposite to the changes of pro-inflammatory levels.
CONCLUSION
The anti-inflammatory response of 6-MP influenced by intestinal microbiota and its metabolites SCFAs, especially butyrate, played an essential role in improving ALL progression.
Topics: Mice; Animals; Propionates; Tumor Necrosis Factor-alpha; Mercaptopurine; Interleukin-6; RNA, Ribosomal, 16S; Chromatography, Liquid; Mice, Inbred DBA; Tandem Mass Spectrometry; Fatty Acids, Volatile; Microbiota; Butyrates; Acetates; Anti-Inflammatory Agents; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 37573688
DOI: 10.1016/j.intimp.2023.110782