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Microbiology Spectrum May 2024Esophageal squamous cell carcinoma (ESCC) is one of the most predominant subtypes of esophageal cancer. The characteristics of the gut microbiome and its metabolites...
Esophageal squamous cell carcinoma (ESCC) is one of the most predominant subtypes of esophageal cancer. The characteristics of the gut microbiome and its metabolites from patients with ESCC have not been adequately studied and discussed. In this study, 40 fecal samples (20 from ESCC patients and 20 from healthy controls) were analyzed by 16S rRNA gene sequencing and untargeted metabolomics. The data sets were analyzed individually and synthesized using various bioinformatics methods. Alpha and beta diversity indicated significant differences in microbial diversity and abundance between ESCC and healthy control feces. At the genus level, the abundance of , , and was significantly increased in ESCC. At the genus level, linear discriminant analysis effect size identified two biomarkers: and . Untargeted metabolomics analysis revealed 307 differential metabolites between ESCC and healthy control feces, with indoles and derivatives, tropane alkaloids, lipids, and lipid-like molecules in higher relative abundance in ESCC feces than in healthy control feces. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that unsaturated fatty acids (FAs), ascorbate and aldarate metabolism, and hypoxia-inducible factor 1 signaling pathway were significantly associated with differential metabolite. Phenylethanolamine and despropionyl p-fluoro fentanyl could be used as reliable biomarkers to differentiate ESCC from healthy control. The correlation analysis showed that may be involved in the synthesis of fatty acyl, carboxylic acids and derivatives, benzenes and substituted derivatives, organic oxygenates, and indoles and derivatives as metabolites. and may be involved in the degradation of indoles and derivatives. , , and may be involved in the synthesis of indoles and derivatives with strong contributions. There is an intricate relationship between the gut microbiome and the levels of several metabolites (e.g., fatty acyls, carboxylic acids and derivatives, indoles, and derivatives). Microbial-associated metabolites can be used as diagnostic biomarkers in therapeutic exploration. Further analysis revealed that , , , and might promote ESCC by regulating the synthesis of indoles and their derivatives. The results of this study provide favorable evidence for the early diagnosis of ESCC and subsequent individualized treatment and targeted interventions.IMPORTANCEWe describe for the first time the differences in fecal microbiome composition and metabolites between patients with esophageal squamous cell carcinoma (ESCC) and healthy controls by 16S rRNA gene sequencing and untargeted metabolomics. The results of this study provide a favorable basis for the early diagnosis of ESCC and subsequent targeted interventional therapy.
Topics: Humans; Feces; Esophageal Squamous Cell Carcinoma; Metabolomics; Gastrointestinal Microbiome; Esophageal Neoplasms; Male; Female; Middle Aged; Bacteria; RNA, Ribosomal, 16S; Biomarkers, Tumor; Aged; Adult
PubMed: 38497715
DOI: 10.1128/spectrum.04012-23 -
Cancers Oct 2023This study aims to combine computed tomography (CT)-based texture analysis (QTA) and a microbiome-based biomarker signature to predict the overall survival (OS) of...
This study aims to combine computed tomography (CT)-based texture analysis (QTA) and a microbiome-based biomarker signature to predict the overall survival (OS) of immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients by analyzing their CT scans ( = 129) and fecal microbiome ( = 58). One hundred and five continuous CT parameters were obtained, where principal component analysis (PCA) identified seven major components that explained 80% of the data variation. Shotgun metagenomics (MG) and ITS analysis were performed to reveal the abundance of bacterial and fungal species. The relative abundance of Bacteroides dorei and Parabacteroides distasonis was associated with long OS (>6 mo), whereas the bacteria Clostridium perfringens and Enterococcus faecium and the fungal taxa Cortinarius davemallochii, Helotiales, Chaetosphaeriales, and Tremellomycetes were associated with short OS (≤6 mo). Hymenoscyphus immutabilis and Clavulinopsis fusiformis were more abundant in patients with high (≥50%) PD-L1-expressing tumors, whereas Thelephoraceae and Lachnospiraceae bacterium were enriched in patients with ICI-related toxicities. An artificial intelligence (AI) approach based on extreme gradient boosting evaluated the associations between the outcomes and various clinicopathological parameters. AI identified MG signatures for patients with a favorable ICI response and high PD-L1 expression, with 84% and 79% accuracy, respectively. The combination of QTA parameters and MG had a positive predictive value of 90% for both therapeutic response and OS. According to our hypothesis, the QTA parameters and gut microbiome signatures can predict OS, the response to therapy, the PD-L1 expression, and toxicity in NSCLC patients treated with ICI, and a machine learning approach can combine these variables to create a reliable predictive model, as we suggest in this research.
PubMed: 37894458
DOI: 10.3390/cancers15205091 -
Naunyn-Schmiedeberg's Archives of... Oct 2023The pharmacology of urolithin C (UroC) on non-alcoholic fatty liver disease (NAFLD) is largely undetermined. We sought to investigate the potential for NAFLD improvement...
The pharmacology of urolithin C (UroC) on non-alcoholic fatty liver disease (NAFLD) is largely undetermined. We sought to investigate the potential for NAFLD improvement by administration of UroC and the underlying mechanisms. We verified the therapeutic effect of UroC on choline-deficient amino acid-defined high fat diet (CDAHFD) induced NAFLD mice via evaluating NAFLD activity score (NAS), AST, ALT, hepatic phosphorylated AMPK, and 4-hydroxynonenal. Oleic acid-induced AML12 cell was appraised by oil red staining and western blotting to explore the effect and mechanism of UroC in vitro. Transcriptional regulation of UroC was explored by liver RNA sequencing, gut microbiota composition was explored by 16SrRNA sequencing, and colorectal tight junctional proteins were detected by western blotting and immunohistochemistry. The detrimental effects of CDAHFD included the increased liver index, AST, ALT, hepatic 4-hydroxynonenal, impaired intestinal mucosal barrier, and most importantly, pathological damage in liver. Oral administration of UroC largely protected against these harmful alterations. Remarkably, both RNA sequencing and western blotting results indicated an activation in hepatic AMPK signaling pathway which was thought to inhibit ferroptosis response to UroC in vivo, while no change were found in AMPK-ferroptosis axis response to UroC in oleic acid-induced AML12 cells, hinted an indispensable linkage between UroC and hepatic AMPK, presumably the gut-liver axis. Furthermore, UroC could neither alleviate lipid deposition nor inhibit ferroptosis in vitro. The 16SrRNA showed UroC partially counteracted the dysbiosis induced by CDAHFD. Specifically, UroC reversed the elevated proportion of Firmicutes/Bacteroidota and enhanced the level of Parabacteroides goldsteinii and Lactobacillus vaginalis, which played a beneficial role in metabolic disorders. Oral administration of Urolithin C protected against the detrimental impact of CDAHFD via regulating AMPK-ferroptosis axis, maintaining intestinal mucosal barrier and counteracting gut dysbiosis.
Topics: Mice; Animals; Non-alcoholic Fatty Liver Disease; AMP-Activated Protein Kinases; Gastrointestinal Microbiome; Dysbiosis; Oleic Acid; Ferroptosis; Liver; Diet, High-Fat; Mice, Inbred C57BL
PubMed: 37126194
DOI: 10.1007/s00210-023-02492-8 -
Cell Communication and Signaling : CCS Sep 2023Several studies show that natural foods are a source of compounds with anticancer properties that affect the gut microbiota and its metabolites. In the present study, we...
BACKGROUND
Several studies show that natural foods are a source of compounds with anticancer properties that affect the gut microbiota and its metabolites. In the present study, we investigate the effect of a delactosed buffalo milk whey by-product (DMW) on colorectal carcinogenesis.
METHODS
The effect of DMW on colorectal carcinoma (CRC) was investigated in the established mouse model of azoxymethane (AOM)-induced colon carcinoma, which closely resembles the human clinical condition of CRC. The effect of DMW on CRC immortalized cell lines was also evaluated to further identify the antineoplastic mechanism of action.
RESULTS
Pretreatment of AOM-treated mice with DMW significantly (P < 0.05) reduced the percentage of mice bearing both aberrant crypt foci with more than four crypts (which are early precancerous lesions that progress to CRC) and tumors. In addition, DMW completely counteracted the effect of AOM on protein expression of caspase-9, cleaved caspase-3 and poly ADP-ribose polymerase in colonic tissue. Administration of DMW alone (i.e. without AOM) resulted in changes in the composition of the gut microbiota, leading to enrichment or depletion of genera associated with health and disease, respectively. DMW was also able to restore AOM-induced changes in specific genera of the gut microbiota. Specifically, DMW reduced the genera Atopobiaceae, Ruminococcus 1 and Lachnospiraceae XPB1014 and increased the genera Parabacteroides and Candidatus Saccharimonas, which were increased and reduced, respectively, by AOM. Blood levels of butyric acid and cancer diagnostic markers (5-methylcytidine and glycerophosphocholine), which were increased by AOM treatment, were reduced by DMW. Furthermore, DMW exerted cytotoxic effects on two human CRC cell lines (HCT116 and HT29) and these effects were associated with the induction of apoptotic signaling.
CONCLUSIONS
Our results suggest that DMW exerts chemopreventive effects and restores the gut microbiota in AOM-induced CRC, and induces cytotoxic effect on CRC cells. DMW could be an important dietary supplement to support a healthy gut microbiota and reduce the prevalence of CRC in humans. Video Abstract.
Topics: Humans; Animals; Mice; Whey; Buffaloes; Milk; Carcinogenesis; Colorectal Neoplasms; Azoxymethane; Butyric Acid
PubMed: 37730576
DOI: 10.1186/s12964-023-01271-5 -
Nutrients Dec 2023Numerous observational studies have documented an association between the circadian rhythm and the composition of the gut microbiota. However, the bidirectional causal...
BACKGROUND
Numerous observational studies have documented an association between the circadian rhythm and the composition of the gut microbiota. However, the bidirectional causal effect of the morning chronotype on the gut microbiota is unknown.
METHODS
A two-sample Mendelian randomization study was performed, using the summary statistics of the morning chronotype from the European Consortium and those of the gut microbiota from the largest available genome-wide association study meta-analysis, conducted by the MiBioGen consortium. The inverse variance-weighted (IVW), weighted mode, weighted median, MR-Egger regression, and simple mode methods were used to examine the causal association between the morning chronotype and the gut microbiota. A reverse Mendelian randomization analysis was conducted on the gut microbiota, which was identified as causally linked to the morning chronotype in the initial Mendelian randomization analysis. Cochran's Q statistics were employed to assess the heterogeneity of the instrumental variables.
RESULTS
Inverse variance-weighted estimates suggested that the morning chronotype had a protective effect on Family ( = -0.072; 95% CI: -0.143, -0.001; = 0.047), Genus ( = -0.112; 95% CI: -0.184, -0.039; = 0.002), and Genus ( = -0.072; 95% CI: -0.143, -0.001; = 0.047). In addition, the gut microbiota (Family (OR = 0.925; 95% CI: 0.857, 0.999; = 0.047), Genus (OR = 0.915; 95% CI: 0.858, 0.975; = 0.007), and Genus (OR = 0.925; 95% CI: 0.857, 0.999; = 0.047)) demonstrated positive effects on the morning chronotype. No significant heterogeneity in the instrumental variables, or in horizontal pleiotropy, was found.
CONCLUSION
This two-sample Mendelian randomization study found that Family , Genus , and Genus were causally associated with the morning chronotype. Further randomized controlled trials are needed to clarify the effects of the gut microbiota on the morning chronotype, as well as their specific protective mechanisms.
Topics: Bacteroides; Bacteroidetes; Chronotype; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis
PubMed: 38201876
DOI: 10.3390/nu16010046 -
Medicine Sep 2023Accumulating evidence has indicated a possible connection between post-stroke cognitive impairment (PSCI) and gut microbiota imbalance. To further investigate this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Accumulating evidence has indicated a possible connection between post-stroke cognitive impairment (PSCI) and gut microbiota imbalance. To further investigate this association, the present work was designed to systematically assess the dissimilarity of gut microbiota between PSCI and healthy individuals or stroke patients.
METHODS
A meta-analysis and systematic review was conducted by searching various databases including PubMed, Web of Science, Embase, VIP, CNKI, and Wangfang for relevant studies. The pooled outcomes were used to estimate the combined dissimilarity of gut microbiota composition between PSCI and healthy individuals or patients with stroke.
RESULTS
Nine eligible studies were included in this meta-analysis. The results showed that there were no significant changes in observed richness indexes (Chao1 and ACE) and Shannon index. Notably, a significant decrease in Simpson index was observed in PSCI patients in comparison to the healthy individuals (-0.31, 95% CI: -0.62 to -0.01, P = 0.04). Moreover, the microbiota composition at the phylum level (increased abundance of Proteobacteria), family level (increased abundance of Bacteroidaceae, Lachnospiraceae, and Veillonellaceae; decreased abundance of Enterobacteriaceae), and genus level (increased abundance of Bacteroides, Clostridium XIVa, and Parabacteroides; decreased abundance of Prevotella and Ruminococcus) was found to be significantly different between PSCI and controls.
CONCLUSION
This meta-analysis suggests a significant shift of observed species and microbiota composition in PSCI compared to healthy individuals or patients with stroke.
Topics: Humans; Gastrointestinal Microbiome; Microbiota; Bacteroides; Clostridiales; Cognitive Dysfunction; Stroke
PubMed: 37657030
DOI: 10.1097/MD.0000000000034764 -
Journal of Agricultural and Food... Dec 2023Our previous study showed that as a substitute for statins, selenium-enriched kiwifruit (Se-Kiwi) might reduce blood lipids and protect the liver in Kunming mice, but...
Our previous study showed that as a substitute for statins, selenium-enriched kiwifruit (Se-Kiwi) might reduce blood lipids and protect the liver in Kunming mice, but the underlying mechanism remains unclear. Metabolic regulation of mammalian intestinal microflora plays an important role in obesity and related diseases induced by a high-fat diet (HFD). Here, samples of serum, liver, colon, and fresh feces from the Se-Kiwi-treated hyperlipidemia C57BL/6J mouse model were collected. Based on metabolome (UHPLC-Q-TOF MS) and gut microbiome (16S rDNA) analyses as well as the integrative analysis of physiological and biochemical indices and pathological data of mice, we aimed to systematically illustrate the gut microbiome and metabolomics mechanism of Se-Kiwi in HFD-induced hyperlipidemic mice. As a result, Se-Kiwi can significantly increase the abundance of potentially beneficial gut bacteria such as , and in the colon and improve hyperlipidemia by regulating the digestion and absorption of vitamins, pyrimidine metabolism, purine metabolism, and other metabolic pathways, which have been confirmed by the following fecal microbiota transplantation experiment. This process was significantly regulated by the , , , , , and genes. These findings may provide a theoretical basis for the research and development of selenium-enriched functional foods in the treatment of hyperlipidemia.
Topics: Mice; Animals; Gastrointestinal Microbiome; Diet, High-Fat; Hyperlipidemias; Selenium; Mice, Inbred C57BL; Metabolomics; Lipid Metabolism; Mammals
PubMed: 38055355
DOI: 10.1021/acs.jafc.3c00108 -
Frontiers in Microbiology 2024Increasing evidence indicates that gut microbiota dysbiosis is related to synovitis and tenosynovitis. Nonetheless, whether these associations are causal is currently...
BACKGROUND
Increasing evidence indicates that gut microbiota dysbiosis is related to synovitis and tenosynovitis. Nonetheless, whether these associations are causal is currently unknown.
OBJECTIVES
A two-sample Mendelian randomization (MR) study was performed to reveal the causality of gut microbiota with synovitis and tenosynovitis.
METHODS
The summary statistical data from a large-scale genome-wide association study (GWAS) were applied as the basis for a two-sample MR analysis. The causal effect was estimated using inverse variance weighted (IVW), weighted median, simple mode, MR-Egger, and weighted mode methods, of which IVW was the important method. Meanwhile, the pleiotropy and heterogeneity were detected and measured using MR-Egger regression, Cochran's Q statistics, funnel plots, and MR pleiotropy residual sum and outlier (MR-PRESSO) methods.
RESULTS
The IVW technique demonstrated that genetically predicted five genera, namely [odds ratio (OR) = 0.999, 95% confidence interval (CI): (0.9977, 0.9998), = 0.019], [OR = 0.999, 95% CI: (0.9971, 0.9999), = 0.036], [OR = 0.998, 95% CI: (0.9954, 0.9999), = 0.041], [OR = 0.997, 95% CI: (0.9955, 0.9994), = 0.011], and [OR = 0.997, 95% CI: (0.9954, 0.9992), = 0.006] were negatively correlated with the risk of synovitis and tenosynovitis, while two other genera, namely [OR = 1.003, 95% CI: (1.0004, 1.0049), = 0.019] and [OR = 1.003, 95% CI: (1.0002, 1.0052), = 0.035] were positively associated with synovitis and tenosynovitis risk. In addition, the data of sensitivity analyses demonstrated that there were no outliers, horizontal pleiotropy, or heterogeneity in the causal relationship of the above-mentioned gut microbiota on synovitis and tenosynovitis ( > 0.05).
CONCLUSION
The results of the study suggested that the gut microbiota was causally involved in synovitis and tenosynovitis and identified specific bacterial taxa that affect synovitis and tenosynovitis, which provide new insights into the pathogenesis underlying the development of synovitis and tenosynovitis mediated by gut microbiota.
PubMed: 38746746
DOI: 10.3389/fmicb.2024.1355725 -
Anaerobe Aug 2023This retrospective study analyzed the susceptibility levels of Bacteroides fragilis group (BFG) in a hospital-based laboratory where disk diffusion test (DDT) was...
OBJECTIVES
This retrospective study analyzed the susceptibility levels of Bacteroides fragilis group (BFG) in a hospital-based laboratory where disk diffusion test (DDT) was routinely performed. Isolates non-susceptible to imipenem and metronidazole by DDT were further investigated using a gradient method.
METHODS
The DDT and MIC susceptibility data of clindamycin, metronidazole, moxifloxacin and imipenem obtained on Brucella blood agar for 1264 non-duplicated isolates during 2020-2021 were analyzed. Species identification was obtained by matrix-assisted laser desorption ionization time-of-flight mass spectrometry and 16S rRNA sequencing. Interpretative agreement of DDT results using the 2015 EUCAST tentative and 2021 CA-SFM breakpoints was compared against MIC as the reference.
RESULTS
The dataset included 604 B. fragilis (483 division I, 121 division II isolates), 415 non-fragilis Bacteroides, 177 Phocaeicola and 68 Parabacteroides. Susceptibility rates for clindamycin (22.1-62.1%) and moxifloxacin (59.9-80.9%) were low and many had no inhibition zones. At the EUCAST and CA-SFM breakpoints, 83.0 and 89.4% were imipenem-susceptible, and 89.6% and 97.4 were metronidazole-susceptible. MIC testing confirmed 11.4% and 2.8% isolates as imipenem-non-susceptible and metronidazole-resistant, respectively. Significant numbers of false-susceptibility and/or false-resistance results were observed at the CA-SFM breakpoint but not the EUCAST breakpoint. Higher rates of imipenem and/or metronidazole resistance were detected in B. fragilis division II, B. caccae, B. ovatus, B. salyersiae, B. stercoris and Parabacteroides. Co-resistance to imipenem and metronidazole was detected in 3 B. fragilis division II isolates.
CONCLUSIONS
The data demonstrated emerging BFG resistance to several important anti-anaerobic antibiotics and highlights the importance of anaerobic susceptibility testing in clinical laboratories to guide therapy.
Topics: Bacteroides; Bacteroides fragilis; Clindamycin; Metronidazole; Moxifloxacin; Hong Kong; Retrospective Studies; RNA, Ribosomal, 16S; Microbial Sensitivity Tests; Anti-Bacterial Agents; Imipenem
PubMed: 37429411
DOI: 10.1016/j.anaerobe.2023.102756 -
Clinical Gastroenterology and... Apr 2024Intestinal fungi have been implicated in the pathogenesis of ulcerative colitis (UC). However, it remains unclear if fungal composition is altered during active versus...
BACKGROUND & AIMS
Intestinal fungi have been implicated in the pathogenesis of ulcerative colitis (UC). However, it remains unclear if fungal composition is altered during active versus quiescent disease.
METHODS
We analyzed clinical and metagenomic data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD), available via the IBD Plexus Program of the Crohn's & Colitis Foundation. We evaluated the fungal composition of fecal samples from 421 patients with UC during clinical activity and remission. Within a longitudinal subcohort (n = 52), we assessed for dynamic taxonomic changes across alterations in clinical activity over time. We examined if fungal amplicon sequence variants and fungal-bacterial relationships were altered during activity versus remission. Finally, we classified activity in UC using a supervised machine learning random forest model trained on fungal abundance data.
RESULTS
During clinical activity, the relative abundance of genus Candida was increased 3.5-fold (P-adj < 1 × 10) compared with during remission. Patients with longitudinal reductions in clinical activity demonstrated parallel reductions in Candida relative abundance (P < .05). Candida relative abundance correlated with Parabacteroides diastonis, Faecalibacterium prausnitzii, and Bacteroides dorei relative abundance (P < .05) during remission; however, these correlations were disrupted during activity. Fungal abundance data successfully classified patients with active or quiescent UC (area under the curve ∼0.80), with Candida relative abundance critical to the success of the model.
CONCLUSIONS
Clinical activity in UC is associated with an increased relative abundance of Candida, cross-sectionally and dynamically over time. The role of fecal Candida as a target for therapeutics in UC should be evaluated.
Topics: Adult; Humans; Colitis, Ulcerative; Mycobiome; Prospective Studies; Crohn Disease; Inflammatory Bowel Diseases; Feces
PubMed: 37802272
DOI: 10.1016/j.cgh.2023.09.023