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Microbiology Spectrum Aug 2022Diabetic nephropathy (DN) is the primary cause of end-stage renal disease. Accumulating studies have implied a critical role for the gut microbiota in diabetes mellitus...
Diabetic nephropathy (DN) is the primary cause of end-stage renal disease. Accumulating studies have implied a critical role for the gut microbiota in diabetes mellitus (DM) and DN. However, the precise roles and regulatory mechanisms of the gut microbiota in the pathogenesis of DN remain largely unclear. In this study, metagenomics sequencing was performed using fecal samples from healthy controls (CON) and type 2 diabetes mellitus (T2DM) patients with or without DN. Fresh fecal samples from 15 T2DM patients without DN, 15 DN patients, and 15 age-, gender-, and body mass index (BMI)-matched healthy controls were collected. The compositions and potential functions of the gut microbiota were estimated. Although no difference of gut microbiota α and β diversity was observed between the CON, T2DM, and DN groups, the relative abundances of butyrate-producing bacteria (, , and Roseburia intestinalis) and potential probiotics ( and ) were significantly reduced in T2DM and DN patients. Besides, Bacteroides stercoris was significantly enriched in fecal samples from patients with DN. Moreover, sp. 26_22 was negatively associated with serum creatinine ( < 0.05). DN patients could be accurately distinguished from CON by sp. CAG_768 (area under the curve [AUC] = 0.941), Bacteroides propionicifaciens (AUC = 0.905), and sp. CAG_715 (AUC = 0.908). DN patients could be accurately distinguished from T2DM patients by , Fusobacterium varium, and sp. MSX73 (AUC = 0.889). Regarding the potential bacterial functions of the gut microbiota, the citrate cycle, base excision repair, histidine metabolism, lipoic acid metabolism, and bile acid biosynthesis were enriched in DN patients, while selenium metabolism and branched-chain amino acid biosynthesis were decreased in DN patients. Gut microbiota imbalance is found in fecal samples from DN patients, in which Roseburia intestinalis is significantly decreased, while Bacteroides stercoris is increased. There is a significant correlation between gut microbiota imbalance and clinical indexes related to lipid metabolism, glucose metabolism, and renal function. The gut microbiota may be predictive factors for the development and progression of DN, although further studies are warranted to illustrate their regulatory mechanisms.
Topics: Bacteroides; Clostridiales; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Gastrointestinal Microbiome; Humans
PubMed: 35863004
DOI: 10.1128/spectrum.00324-22 -
Cell Host & Microbe May 2023Environmental exposures are a major risk factor for developing colorectal cancer, and the gut microbiome may serve as an integrator of such environmental risk. To study...
Environmental exposures are a major risk factor for developing colorectal cancer, and the gut microbiome may serve as an integrator of such environmental risk. To study the microbiome associated with premalignant colon lesions, such as tubular adenomas (TAs) and sessile serrated adenomas (SSAs), we profiled stool samples from 971 participants undergoing colonoscopy and paired these data with dietary and medication history. The microbial signatures associated with either SSA or TA are distinct. SSA associates with multiple microbial antioxidant defense systems, whereas TA associates with a depletion of microbial methanogenesis and mevalonate metabolism. Environmental factors, such as diet and medications, link with the majority of identified microbial species. Mediation analyses found that Flavonifractor plautii and Bacteroides stercoris transmit the protective or carcinogenic effects of these factors to early carcinogenesis. Our findings suggest that the unique dependencies of each premalignant lesion may be exploited therapeutically or through dietary intervention.
Topics: Humans; Colonic Polyps; Colorectal Neoplasms; Colonoscopy; Adenoma
PubMed: 37130517
DOI: 10.1016/j.chom.2023.04.007 -
Frontiers in Immunology 2022In clinical practice, fecal microbiota transplantation (FMT) has been used to treat inflammatory bowel disease (IBD), and has shown certain effects. However, the...
In clinical practice, fecal microbiota transplantation (FMT) has been used to treat inflammatory bowel disease (IBD), and has shown certain effects. However, the selection of FMT donors and the mechanism underlying the effect of FMT intervention in IBD require further exploration. In this study, dextran sodium sulfate (DSS)-induced colitis mice were used to determine the differences in the protection of colitis symptoms, inflammation, and intestinal barrier, by FMT from two donors. Intriguingly, pre-administration of healthy bacterial fluid significantly relieved the symptoms of colitis compared to the ulcerative colitis (UC) bacteria. In addition, healthy donor (HD) bacteria significantly reduced the levels of inflammatory markers Myeloperoxidase (MPO) and Eosinophil peroxidase (EPO), and various pro-inflammatory factors, in colitis mice, and increased the secretion of the anti-inflammatory factor IL-10. Metagenomic sequencing indicated higher species diversity and higher abundance of anti-inflammatory bacteria in the HD intervention group, including , , , short-chain fatty acids (SCFAs)-producing bacterium , and secondary bile acids (SBAs)-producing bacterium . In the UC intervention group, the SCFA-producing bacterium , IBD-related bacterium , , and the conditional pathogen , were more abundant. Metabolomics analysis showed that the two types of FMT significantly modulated the metabolism of DSS-induced mice. Moreover, compared with the UC intervention group, indoleacetic acid and unsaturated fatty acids (DHA, DPA, and EPA) with anti-inflammatory effects were significantly enriched in the HD intervention group. In summary, these results indicate that FMT can alleviate the symptoms of colitis, and the effect of HD intervention is better than that of UC intervention. This study offers new insights into the mechanisms of FMT clinical intervention in IBD.
Topics: Animals; Anti-Inflammatory Agents; Bacteria; Colitis; Colitis, Ulcerative; Dextran Sulfate; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Humans; Mice
PubMed: 35237276
DOI: 10.3389/fimmu.2022.836542 -
Frontiers in Cellular and Infection... 2022In this study, we examined the changes to the composition and function of the gut microbiota from patients with metabolic dysfunction-associated fatty liver disease...
PURPOSE
In this study, we examined the changes to the composition and function of the gut microbiota from patients with metabolic dysfunction-associated fatty liver disease (MAFLD).We compared patients in a case group (liver stiffness (LSM) ≥ 7.4 kPa) with a matched control group (LSM < 7.4 kPa) and investigated the correlation between characteristics of the microbiota and other biochemical indicators.
METHODS
The study looked at a total of 85 men with MAFLD, 17 of whom were in the case group and 68 of whom were in the control group. We measured waist circumference, blood pressure, and body mass index, as well as clinical parameters including liver stiffness, enzyme levels, cholesterol levels, and fat attenuation. Whole-genome shotgun sequencing technology and the MetaCyc database were then used to detect the composition and major pathways of the gut microbiota for each patient. Statistical analyses were performed, including the chi-square test, the student's t-test, the Wilcoxon rank-sum test, and the Mann-Whitney test.
RESULTS
Whole-genome sequencing showed that the composition of the gut microbiota in patients with an LSM of above 7.4 kPa was significantly different to that of the control group. There were seven bacterial species that were different between the two groups. Prevotella copri, Phascolarctobacterium succinatutens, Eubacterium biforme, and Collinsella aerofaciens were enriched in the case group (P < 0.05). Conversely, Bacteroides coprocola, Bacteroides stercoris and Clostridiales bacterium 1_7_47FAA were decreased in the case group (P < 0.05). Furthermore, after removing low abundance pathways, a total of 32 microbial pathways were found to be significantly different between the two groups. Most pathways enriched in the case group over the control were related to biosynthesis of metabolites including amino acids, vitamins, nucleosides, and nucleotides. Conclusion. The composition and function of the gut microbiota in patients with increased liver stiffness are significantly altered. This observation may provide new avenues to better understand the mechanism of liver fibrosis.
Topics: Bacteria; Clostridiales; Eubacterium; Gastrointestinal Microbiome; Humans; Liver; Male
PubMed: 35992168
DOI: 10.3389/fcimb.2022.873048 -
Microbiome Aug 2023A growing body of evidence suggests that the gut microbiota is strongly linked to general human health. Microbiome-directed interventions, such as diet and exercise, are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A growing body of evidence suggests that the gut microbiota is strongly linked to general human health. Microbiome-directed interventions, such as diet and exercise, are acknowledged as a viable and achievable strategy for preventing disorders and improving human health. However, due to the significant inter-individual diversity of the gut microbiota between subjects, lifestyle recommendations are expected to have distinct and highly variable impacts to the microbiome structure.
RESULTS
Here, through a large-scale meta-analysis including 1448 shotgun metagenomics samples obtained longitudinally from 396 individuals during lifestyle studies, we revealed Bacteroides stercoris, Prevotella copri, and Bacteroides vulgatus as biomarkers of microbiota's resistance to structural changes, and aromatic and non-aromatic amino acid biosynthesis as important regulator of microbiome dynamics. We established criteria for distinguishing between significant compositional changes from normal microbiota fluctuation and classified individuals based on their level of response. We further developed a machine learning model for predicting "responders" and "non-responders" independently of the type of intervention with an area under the curve of up to 0.86 in external validation cohorts of different ethnicities.
CONCLUSIONS
We propose here that microbiome-based stratification is possible for identifying individuals with highly plastic or highly resistant microbial structures. Identifying subjects that will not respond to generalized lifestyle therapeutic interventions targeting the restructuring of gut microbiota is important to ensure that primary end-points of clinical studies are reached. Video Abstract.
Topics: Humans; Microbiota; Gastrointestinal Microbiome; Biomarkers; Diet; Life Style
PubMed: 37553697
DOI: 10.1186/s40168-023-01604-z -
Cell Host & Microbe Sep 2021Bacterial ADP-ribosyltransferases (ADPRTs) have been described as toxins involved in pathogenesis through the modification of host proteins. Here, we report that ADPRTs...
Bacterial ADP-ribosyltransferases (ADPRTs) have been described as toxins involved in pathogenesis through the modification of host proteins. Here, we report that ADPRTs are not pathogen restricted but widely prevalent in the human gut microbiome and often associated with phage elements. We validated their biochemical activity in a large clinical isolate collection and further examined Bxa, a highly abundant ADPRT in Bacteroides. Bxa is expressed, secreted, and enzymatically active in Bacteroides and can ADP-ribosylate non-muscle myosin II proteins. Addition of Bxa to epithelial cells remodeled the actin cytoskeleton and induced secretion of inosine. Bxa-encoding B. stercoris can use inosine as a carbon source and colonizes the gut to significantly greater numbers than a bxa-deleted strain in germ-free and altered Schaedler flora (ASF) mice. Colonization correlated with increased inosine concentrations in the feces and tissues. Altogether, our results show that ADPRTs are abundant in the microbiome and act as bacterial fitness factors.
Topics: ADP Ribose Transferases; Actin Cytoskeleton; Animals; Bacteriophages; Bacteroides; Bacteroides thetaiotaomicron; Caco-2 Cells; Cell Line, Tumor; Epithelial Cells; Feces; Female; Gastrointestinal Microbiome; Germ-Free Life; HT29 Cells; Humans; Inosine; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Myosin Heavy Chains
PubMed: 34403684
DOI: 10.1016/j.chom.2021.07.011 -
Microbiology Spectrum Sep 2023Acute pancreatitis (AP) is a type of digestive system disease with high mortality. Previous studies have shown that gut microbiota can participate in developing and...
Acute pancreatitis (AP) is a type of digestive system disease with high mortality. Previous studies have shown that gut microbiota can participate in developing and treating acute pancreatitis by affecting the host's metabolism. In this study, we followed 20 AP patients to generate longitudinal gut microbiota profiles and activity during disease (before treatment, on the third day of treatment, and 1 month after discharge). We analyzed species composition and metabolic pathways' changes across the treatment phase, severity, and etiology. The diversity of the gut microbiome of patients with AP did not show much variation with treatment. In contrast, the metabolic functions of the gut microbiota, such as the essential chemical reactions that produce energy and maintain life, were partially reinstated after treatment. The severe AP (SAP) patients contained less beneficial bacteria (i.e., , and ) and weaker sugar degradation function than mild AP patients before treatment. Moreover, etiology was one of the drivers of gut microbiome composition and explained the 3.54% variation in species' relative abundance. The relative abundance of pathways related to lipid synthesis was higher in the gut of hyperlipidemia AP patients than in biliary AP patients. The composition and functional profiles of the gut microbiota reflect the severity and etiology of AP. Otherwise, we also identified bacterial species associated with SAP, i.e., sp 57_20 and , which have the potential to identify the SAP at an early stage. IMPORTANCE Acute pancreatitis (AP) is a type of digestive system disease with high mortality. Previous studies have shown that gut microbiota can participate in the development and treatment of acute pancreatitis by affecting the host's metabolism. However, fewer studies acquired metagenomic sequencing data to associate species to functions intuitively and performed longitudinal analysis to explore how gut microbiota influences the development of AP. We followed 20 AP patients to generate longitudinal gut microbiota profiles and activity during disease and studied the differences in intestinal flora under different severities and etiologies. We have two findings. First, the gut microbiota profile has the potential to identify the severity and etiology of AP at an early stage. Second, gut microbiota likely acts synergistically in the development of AP. This study provides a reference for characterizing the driver flora of severe AP to identify the severity of acute pancreatitis at an early stage.
PubMed: 37698429
DOI: 10.1128/spectrum.00829-23 -
Food & Nutrition Research 2022Metabolic diseases have been related to gut microbiota, and new knowledge indicates that diet impacts host metabolism through the gut microbiota. Identifying specific...
BACKGROUND
Metabolic diseases have been related to gut microbiota, and new knowledge indicates that diet impacts host metabolism through the gut microbiota. Identifying specific gut bacteria associated with both diet and metabolic risk markers may be a potential strategy for future dietary disease prevention. However, studies investigating the association between the gut microbiota, diet, and metabolic markers in healthy individuals are scarce.
OBJECTIVE
We explored the relationship between a panel of gut bacteria, dietary intake, and metabolic and anthropometric markers in healthy adults.
DESIGN
Forty-nine volunteers were included in this cross-sectional study. Measures of glucose, serum triglyceride, total cholesterol, hemoglobin A1c (HbA1c), blood pressure (BP), and body mass index (BMI) were collected after an overnight fast, in addition to fecal samples for gut microbiota analyzes using a targeted approach with a panel of 48 bacterial DNA probes and assessment of dietary intake by a Food Frequency Questionnaire (FFQ). Correlations between gut bacteria, dietary intake, and metabolic and anthropometric markers were assessed by Pearson's correlation. Gut bacteria varying according to dietary intake and metabolic markers were assessed by a linear regression model and adjusted for age, sex, and BMI.
RESULTS
Of the 48 gut bacteria measured, 24 and 16 bacteria correlated significantly with dietary intake and metabolic and/or anthropometric markers, respectively. Gut bacteria including , spp., and differed according to the intake of the food components, fiber, sodium, saturated fatty acids, and dietary indices, and metabolic markers (BP and total cholesterol) after adjustments. Notably, correlated positively with the intake of fiber, grain products, and vegetables, and higher abundance was associated with higher adherence to Healthy Nordic Food Index (HNFI) and lower diastolic BP after adjustment.
CONCLUSION
Our findings highlight the relationship between the gut microbiota, diet, and metabolic markers in healthy individuals. Further investigations are needed to address whether these findings are causally linked and whether targeting these gut bacteria can prevent metabolic diseases.
PubMed: 35844956
DOI: 10.29219/fnr.v66.8580 -
Frontiers in Microbiology 2023Osteoarthritis (OA) is a kind of chronic, degenerative disorder with unknown causes. In this study, we aimed to improve our understanding of the gut microbiota profile...
INTRODUCTION
Osteoarthritis (OA) is a kind of chronic, degenerative disorder with unknown causes. In this study, we aimed to improve our understanding of the gut microbiota profile in patients with knee OA.
METHODS
16S rDNA gene sequencing was performed to detect the gut microbiota in fecal samples collected from the patients with OA ( = 32) and normal control (NC, = 57). Then the metagenomic sequencing was used to identify the genes or functions linked with gut microbial changes at the species level in the fecal samples from patients with OA and NC groups.
RESULTS
The Proteobacteria was identified as dominant bacteria in OA group. We identified 81 genera resulted significantly different in abundance between OA and NC. The abundance of , , , , and showed significant decrease in the OA compared to the NC. The abundance of genera , , and were increasing in the OA group, and the families , , and were increasing in the NC. The metagenomic sequencing showed that the abundance of , and at the species level were significantly decreasing in the OA, and the abundance of , , and were significantly increased in OA.
DISCUSSION
The results of our study interpret a comprehensive profile of the gut microbiota in patients with knee OA and offer the evidence that the cartilage-gut-microbiome axis could play a crucial role in underlying the mechanisms and pathogenesis of OA.
PubMed: 37250055
DOI: 10.3389/fmicb.2023.1153424 -
Journal of Clinical Medicine Apr 2021Fecal microbiota transplantation following triple-antibiotic therapy (amoxicillin/fosfomycin/metronidazole) improves dysbiosis caused by reduced Bacteroidetes diversity...
Fecal microbiota transplantation following triple-antibiotic therapy (amoxicillin/fosfomycin/metronidazole) improves dysbiosis caused by reduced Bacteroidetes diversity in patients with ulcerative colitis (UC). We investigated the correlation between Bacteroidetes species abundance and UC activity. Fecal samples from 34 healthy controls and 52 patients with active UC (Lichtiger's clinical activity index ≥5 or Mayo endoscopic subscore ≥1) were subjected to next-generation sequencing with as a target in bacterial metagenome analysis. A multiplex gene expression assay using colonoscopy-harvested mucosal tissues determined the involvement of Bacteroidetes species in the mucosal immune response. In patients with UC, six Bacteroides species exhibited significantly lower relative abundance, and twelve Bacteroidetes species were found significantly correlated with at least one metric of disease activity. The abundance of five Bacteroidetes species (, , , , and ) was correlated with three metrics, and their cumulative relative abundance was strongly correlated with the sum of Mayo endoscopic subscore (R = -0.71, = 2 × 10). Five genes (, , , , and ) associated with UC pathogenesis were expressed by the 12 key species. The loss of key species may exacerbate UC activity, serving as potential biomarkers.
PubMed: 33920646
DOI: 10.3390/jcm10081749