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Nutrients Aug 2021Dietary habits and gut microbiota play an essential role in non-alcoholic fatty liver disease (NAFLD) and related factors such as insulin resistance and de novo...
Dietary habits and gut microbiota play an essential role in non-alcoholic fatty liver disease (NAFLD) and related factors such as insulin resistance and de novo lipogenesis. In this study, we investigated the protective effects of CBA7346, isolated from the gut of healthy Koreans, on mice with high-fat diet (HFD)-induced NAFLD. Administration of CBA7346 reduced body and liver weight gain, serum alanine aminotransferase and aspartate aminotransferase levels, liver steatosis, and liver triglyceride levels in mice on an HFD; the strain also decreased homeostatic model assessment for insulin resistance values, as well as serum cholesterol, triglyceride, lipopolysaccharide, leptin, and adiponectin levels in mice on an HFD. Moreover, CBA7346 controlled fatty liver disease by attenuating steatosis and inflammation and regulating de novo lipogenesis-related proteins in mice on an HFD. Taken together, these findings suggest that CBA7346 ameliorates HFD-induced NAFLD by reducing insulin resistance and regulating de novo lipogenesis in obese mice.
Topics: Animals; Bacteroides; Diet, High-Fat; Disease Models, Animal; Fatty Liver; Gastrointestinal Microbiome; Humans; Insulin Resistance; Lipogenesis; Liver; Male; Mice; Mice, Inbred C57BL
PubMed: 34578867
DOI: 10.3390/nu13092989 -
Signal Transduction and Targeted Therapy Sep 2023Whether the alternated microbiota in the gut contribute to the risk of allograft rejection (AR) and pulmonary infection (PI) in the setting of lung transplant recipients...
Whether the alternated microbiota in the gut contribute to the risk of allograft rejection (AR) and pulmonary infection (PI) in the setting of lung transplant recipients (LTRs) remains unexplored. A prospective multicenter cohort of LTRs was identified in the four lung transplant centers. Paired fecal and serum specimens were collected and divided into AR, PI, and event-free (EF) groups according to the diagnosis at sampling. Fecal samples were determined by metagenomic sequencing. And metabolites and cytokines were detected in the paired serum to analyze the potential effect of the altered microbiota community. In total, we analyzed 146 paired samples (AR = 25, PI = 43, and EF = 78). Notably, we found that the gut microbiome of AR followed a major depletion pattern with decreased 487 species and compositional diversity. Further multi-omics analysis showed depleted serum metabolites and increased inflammatory cytokines in AR and PI. Bacteroides uniformis, which declined in AR (2.4% vs 0.6%) and was negatively associated with serum IL-1β and IL-12, was identified as a driven specie in the network of gut microbiome of EF. Functionally, the EF specimens were abundant in probiotics related to mannose and cationic antimicrobial peptide metabolism. Furthermore, a support-vector machine classifier based on microbiome, metabolome, and clinical parameters highly predicted AR (AUPRC = 0.801) and PI (AUPRC = 0.855), whereby the microbiome dataset showed a particularly high diagnostic power. In conclusion, a disruptive gut microbiota showed a significant association with allograft rejection and infection and with systemic cytokines and metabolites in LTRs.
Topics: Humans; Gastrointestinal Microbiome; Prospective Studies; Lung Transplantation; Cytokines; Allografts
PubMed: 37652953
DOI: 10.1038/s41392-023-01515-3 -
Microorganisms Jul 2021In our previous study the enrichment of the intestinal proteome of type 1 diabetes (T1D) children with proteins was observed, which led us to our current study that...
In our previous study the enrichment of the intestinal proteome of type 1 diabetes (T1D) children with proteins was observed, which led us to our current study that aimed to isolate and characterize species from fecal samples of T1D and control children. Repetitive sequence-based PCR (rep-PCR) was used for typing the isolated species. The antibiotic susceptibility and mucinolytic activity of the isolates was determined. The quantification of specific bacterial groups in the fecal samples was determined by qPCR. The ability to adhere and invade the human colonic cell line HT29-MTX-E12 of strains of , and was determined and their whole genome sequencing was performed. The results showed similar numbers of species in T1D and control samples, but unique species and a higher recovery of from T1D samples was observed. Rep-PCR grouped the different species, but no discrimination by origin was achieved. T1D children showed a significant increase in and a depletion in sp. All tested , and were able to adhere to HT29-MTX-E12 cells but significant differences ( < 0.05) in the ability to invade was observed. The highest ability to invade was exhibited by PtF D14MH1 and PtFD16P1, while strains were unable to invade. The damage to tight junctions was also observed. The presence of sp. inhibited the invasion ability of PtF D14MH1 but not PtFD16P1. Sequences of agonist peptides of the human natural preproinsulin and the insulin B chain insB:9-23 peptide mimics were identified. The results reported in our study stresses the continued efforts required to clarify the link between T1D and gut microbiota.
PubMed: 34361871
DOI: 10.3390/microorganisms9071436 -
Scientific Reports Aug 2023Gut microbiota metabolites have been mechanistically linked to inflammatory pathway activation and atherosclerosis, which are major causes of vascular stiffness (VS)....
Gut microbiota metabolites have been mechanistically linked to inflammatory pathway activation and atherosclerosis, which are major causes of vascular stiffness (VS). Aiming to investigate if the gut microbiome might be involved in VS development, we performed a cross-sectional study (n = 3,087), nested within the population-based European Prospective Investigations into Cancer and Nutrition (EPIC) Potsdam. We investigated the correlation of the gut microbiota (alpha diversity and taxa abundance) with 3 vascular stiffness measures: carotid-femoral (PWV), aortic augmentation index (AIX) and ankle-brachial index (ABI). Shannon index was not significantly associated with VS but the number of observed Amplicon Sequence Variants (ASV) was positively associated with PWV and AIX. We found a total of 19 ASVs significantly associated with at least one VS measure in multivariable-adjusted models. One ASV (classified as Sutterella wadsworthensis) was associated with 2 VS measures, AIX (- 0.11 ± 0.04) and PWV (-0.14 ± 0.03). Other examples of ASVs associated with VS were Collinsella aerofaciens, previously reported to be affected by diet and Bacteroides uniformis, commercially available as probiotics. In conclusion, our study suggests a potential role of individual components of the gut microbiota in the aetiology of VS.
Topics: Humans; Gastrointestinal Microbiome; Cross-Sectional Studies; Prospective Studies; Vascular Stiffness; Cancer Vaccines
PubMed: 37587126
DOI: 10.1038/s41598-023-40178-6 -
Frontiers in Immunology 2022The consumption of plant-based bioactive compounds modulates the gut microbiota and interacts with the innate and adaptive immune responses associated with metabolic...
Cranberry polyphenols and agave agavins impact gut immune response and microbiota composition while improving gut barrier function, inflammation, and glucose metabolism in mice fed an obesogenic diet.
The consumption of plant-based bioactive compounds modulates the gut microbiota and interacts with the innate and adaptive immune responses associated with metabolic disorders. The present study aimed to evaluate the effect of cranberry polyphenols (CP), rich in flavonoids, and agavins (AG), a highly branched agave-derived neo-fructans, on cardiometabolic response, gut microbiota composition, metabolic endotoxemia, and mucosal immunomodulation of C57BL6 male mice fed an obesogenic high-fat and high-sucrose (HFHS) diet for 9 weeks. Interestingly, CP+AG-fed mice had improved glucose homeostasis. Oral supplementation with CP selectively and robustly (five-fold) increases the relative abundance of , a beneficial bacteria associated with metabolic health. AG, either alone or combined with CP (CP+AG), mainly stimulated the glycan-degrading bacteria , , , and This increase of glycan-degrading bacteria was consistent with a significantly increased level of butyrate in obese mice receiving AG, as compared to untreated counterparts. CP+AG-supplemented HFHS-fed mice had significantly lower levels of plasma LBP than HFHS-fed controls, suggesting blunted metabolic endotoxemia and improved intestinal barrier function. Gut microbiota and derived metabolites interact with the immunological factors to improve intestinal epithelium barrier function. Oral administration of CP and AG to obese mice contributed to dampen the pro-inflammatory immune response through different signaling pathways. CP and AG, alone or combined, increased toll-like receptor (TLR)-2 () expression, while decreasing the expression of interleukin 1ß (ILß1) in obese mice. Moreover, AG selectively promoted the anti-inflammatory marker , while CP increased the expression of NOD-like receptor family pyrin domain containing 6 () inflammasome. The intestinal immune system was also shaped by dietary factor recognition. Indeed, the combination of CP+AG significantly increased the expression of aryl hydrocarbon receptors (). Altogether, both CP and AG can shape gut microbiota composition and regulate key mucosal markers involved in the repair of epithelial barrier integrity, thereby attenuating obesity-associated gut dysbiosis and metabolic inflammation and improving glucose homeostasis.
Topics: Agave; Animals; Diet, High-Fat; Endotoxemia; Glucose; Immunity; Inflammation; Mice; Mice, Inbred C57BL; Mice, Obese; Microbiota; Plant Extracts; Polyphenols; Vaccinium macrocarpon
PubMed: 36052065
DOI: 10.3389/fimmu.2022.871080 -
Archives of Microbiology Aug 2022Two bacterial strains, KH365_2 and KH569_7, were isolated from the cecum contents of wild-derived house mice. The strains were characterized as Gram-negative,...
Two bacterial strains, KH365_2 and KH569_7, were isolated from the cecum contents of wild-derived house mice. The strains were characterized as Gram-negative, rod-shaped, strictly anaerobic, and non-motile. Phylogenetic analysis based on 16S rRNA gene sequences revealed that both strains were most closely related to Bacteroides uniformis ATCC 8492. Whole genome sequences of KH365_2 and KH569_7 strains have a DNA G + C content of 46.02% and 46.03% mol, respectively. Most morphological and biochemical characteristics did not differ between the newly isolated strains and classified Bacteroides strains. However, the average nucleotide identity (ANI) and dDNA-DNA hybridization (dDDH) values clearly distinguished the two strains from described members of the genus Bacteroides. Here, we present the phylogeny, morphology, and physiology of a novel species of the genus Bacteroides and propose the name Bacteroides muris sp. nov., with KH365_2 (DSM 114231 = CCUG 76277) as type strain.
Topics: Animals; Bacterial Typing Techniques; Bacteroides; Cecum; DNA, Bacterial; Fatty Acids; Gastropoda; Mice; Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis, DNA
PubMed: 35939214
DOI: 10.1007/s00203-022-03148-6 -
Gut Microbes Nov 2020glucans are the dietary nutrients present in oats, barley, algae, and mushrooms. The macromolecules are well known for their immune-modulatory activity; however, how the...
glucans are the dietary nutrients present in oats, barley, algae, and mushrooms. The macromolecules are well known for their immune-modulatory activity; however, how the human gut bacteria digest them is vaguely understood. In this study, JCM 13288 was found to grow on laminarin, pustulan, and porphyran. We sequenced the genome of the strain, which was about 5.05 megabase pairs and contained 4868 protein-coding genes. On the basis of growth patterns of the bacterium, two putative polysaccharide utilization loci for glucans were identified from the genome, and associated four putative genes were cloned, expressed, purified, and characterized. Three glycoside hydrolases (GHs) that were endo-acting enzymes (GH16, GH30, and GH158), and one which was an exo-acting (GH3) enzyme. The GH3, GH16, and GH158 can cleave linear exo/endo- 1-3 linkages while GH30 can digest endo- 1-6 linkages. GH30 and GH158 were further explored for their roles in digesting glucans and generation of oligosaccharides, respectively. The GH30 predominately found to cleave long chain 1-6 linked glucans, and obtained final product was gentiobiose. The GH158 used for producing oligosaccharides varying from degree of polymerization 2 to 7 from soluble curdlan. We demonstrated that these oligosaccharides can be utilized by gut bacteria, which either did not grow or poorly grew on laminarin. Thus, JCM 13288 is not only capable of utilizing glucans but also shares these glycans with human gut bacteria for potentially maintaining the gut microbial homeostasis.
Topics: Bacteroides; Carbohydrate Conformation; Gastrointestinal Microbiome; Genetic Loci; Genome, Bacterial; Glycoside Hydrolases; Gram-Positive Bacteria; Microbial Interactions; Oligosaccharides; Polysaccharides; beta-Glucans
PubMed: 33043794
DOI: 10.1080/19490976.2020.1826761 -
The Journal of Biological Chemistry Nov 2018The glycoside hydrolases encoded by the human gut microbiome play an integral role in processing a variety of exogenous and endogenous glycoconjugates. Here we present...
The glycoside hydrolases encoded by the human gut microbiome play an integral role in processing a variety of exogenous and endogenous glycoconjugates. Here we present three structurally and functionally distinct β-glucuronidase (GUS) glycoside hydrolases from a single human gut commensal microbe, We show using nine crystal structures, biochemical, and biophysical data that whereas these three proteins share similar overall folds, they exhibit different structural features that create three structurally and functionally unique enzyme active sites. Notably, quaternary structure plays an important role in creating distinct active site features that are hard to predict via structural modeling methods. The enzymes display differential processing capabilities toward glucuronic acid-containing polysaccharides and SN-38-glucuronide, a metabolite of the cancer drug irinotecan. We also demonstrate that GUS-specific and nonselective inhibitors exhibit varying potencies toward each enzyme. Together, these data highlight the diversity of GUS enzymes within a single gut commensal and advance our understanding of how structural details impact the specific roles microbial enzymes play in processing drug-glucuronide and glycan substrates.
Topics: Amino Acid Sequence; Bacteroides; Catalytic Domain; Enzyme Inhibitors; Gastrointestinal Microbiome; Glucaric Acid; Glucuronidase; Humans; Isoenzymes; Protein Conformation
PubMed: 30301767
DOI: 10.1074/jbc.RA118.005414 -
MSystems Apr 2023Human gut dysbiosis is associated with type 2 diabetes mellitus (T2DM); however, the gut microbiome in pregnant women with pregestational type 2 diabetes mellitus (PGDM)...
Human gut dysbiosis is associated with type 2 diabetes mellitus (T2DM); however, the gut microbiome in pregnant women with pregestational type 2 diabetes mellitus (PGDM) remains unexplored. We investigated the alterations in the gut microbiota composition in pregnant women with or without PGDM. The gut microbiota was examined using 16S rRNA sequencing data of 234 maternal fecal samples that were collected during the first (T1), second (T2), and third (T3) trimesters. The PGDM group presented a reduction in the number of gut bacteria taxonomies as the pregnancies progressed. Linear discriminant analyses revealed that , , and Roseburia intestinalis were enriched in the PGDM group, whereas Bacteroides vulgatus, Faecalibacterium prausnitzii, Eubacterium rectale, Bacteroides uniformis, Eubacterium eligens, , Bacteroides fragilis, , , R-7, Roseburia inulinivorans, Streptococcus oralis, Prevotella melaninogenica, Neisseria perflava, Bacteroides ovatus, Bacteroides caccae, Veillonella dispar, and Haemophilus parainfluenzae were overrepresented in the control group. Correlation analyses showed that the PGDM-enriched taxa were correlated with higher blood glucose levels during pregnancy, whereas the taxonomic biomarkers of normoglycemic pregnancies exhibited negative correlations with glycemic traits. The microbial networks in the PGDM group comprised weaker microbial interactions than those in the control group. Our study reveals the distinct characteristics of the gut microbiota composition based on gestational ages between normoglycemic and PGDM pregnancies. Further longitudinal research involving women with T2DM at preconception stages and investigations using shotgun metagenomic sequencing should be performed to elucidate the relationships between specific bacterial functions and PGDM metabolic statuses during pregnancy and to identify potential therapeutic targets. The incidence of pregestational type 2 diabetes mellitus (PGDM) is increasing, with high rates of serious adverse maternal and neonatal outcomes that are strongly correlated with hyperglycemia. Recent studies have shown that type 2 diabetes mellitus is associated with gut microbial dysbiosis; however, the gut microbiome composition and its associations with the metabolic features of patients with PGDM remain largely unknown. In this study, we investigated the changes in the gut microbiota composition in pregnant women with and without PGDM. We identified differential taxa that may be correlated with maternal metabolic statuses during pregnancy. Additionally, we observed that the number of taxonomic and microbial networks of gut bacteria were distinctly reduced in women with hyperglycemia as their pregnancies progressed. These results extend our understanding of the associations between the gut microbial composition, PGDM-related metabolic changes, and pregnancy outcomes.
Topics: Infant, Newborn; Humans; Female; Pregnancy; Gastrointestinal Microbiome; Diabetes Mellitus, Type 2; Pregnant Women; Dysbiosis; RNA, Ribosomal, 16S; Pregnancy Outcome; Hyperglycemia
PubMed: 36853013
DOI: 10.1128/msystems.01146-22 -
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