-
World Journal of Gastroenterology May 2021Gut microbiota dysbiosis is reportedly actively involved in autoimmune diseases such as type 1 diabetes mellitus (T1DM). However, the alterations in the gut microbiota... (Observational Study)
Observational Study
BACKGROUND
Gut microbiota dysbiosis is reportedly actively involved in autoimmune diseases such as type 1 diabetes mellitus (T1DM). However, the alterations in the gut microbiota and their correlation with fasting blood glucose (FBG) in Chinese children with T1DM remain unclear.
AIM
To investigate alterations in the gut microbiota in Chinese children with T1DM and their associations with clinical indicators.
METHODS
Samples from 51 children with T1DM and 47 age-matched and gender-matched healthy controls were obtained, to explore the structural and functional alterations in the fecal microbiota. The V3-V4 regions of the 16S rRNA gene were sequenced on a MiSeq instrument, and the association with FBG were analyzed.
RESULTS
We found that the bacterial diversity was significantly increased in the T1DM-associated fecal microbiota, and changes in the microbial composition were observed at different taxonomic levels. The T1DM-reduced differential taxa, such as ATCC8482, , , and , were negatively correlated with FBG, while the T1DM-enriched taxa, such as , group, , and , were positively correlated with FBG. ATCC8482, , the group, and , either alone or in combination, could be used as noninvasive diagnostic biomarkers to discriminate children with T1DM from healthy controls. In addition, the functional changes in the T1DM-associated fecal microbiota also suggest that these fecal microbes were associated with altered functions and metabolic activities, such as glycan biosynthesis and metabolism and lipid metabolism, which might play vital roles in the pathogenesis and development of T1DM.
CONCLUSION
Our present comprehensive investigation of the T1DM-associated fecal microbiota provides novel insights into the pathogenesis of the disease and sheds light on the diagnosis and treatment of T1DM.
Topics: Bacteroides; Child; China; Clostridiales; Diabetes Mellitus, Type 1; Dysbiosis; Gastrointestinal Microbiome; Humans; RNA, Ribosomal, 16S
PubMed: 34040330
DOI: 10.3748/wjg.v27.i19.2394 -
Applied and Environmental Microbiology Jan 2012Besides conferring some health benefit to the host, a bacterial strain must present an unambiguous safety status to be considered a probiotic. We here present the...
Besides conferring some health benefit to the host, a bacterial strain must present an unambiguous safety status to be considered a probiotic. We here present the preliminary safety evaluation of a new Bacteroides xylanisolvens strain (DSM 23964) isolated from human feces. First results suggest that it may be able to provide probiotic health benefits. Its identity was confirmed by biochemical analysis, by sequencing of its 16S rRNA genes, and by DNA-DNA hybridization. Virulence determinants known to occur in the genus Bacteroides, such the bft enterotoxin and other enzymatic activities involved in the degradation of the extracellular matrix and the capsular polysaccharide PS A, were absent in this strain. The investigation of the antibiotic susceptibility indicated that strain DSM 23964 was sensitive to metronidazole, meropenem agents, and clindamycin. Resistance to penicillin and ampicillin was identified to be conferred by the β-lactamase cepA gene and could therefore be restored by adding β-lactamase inhibitors. The localization of the cepA gene in the genome of strain DSM 23964 and the absence of detectable plasmids further suggest that a transfer of β-lactamase activity or the acquisition of other antibiotic resistances are highly improbable. Taken together, the presented data indicate that the strain B. xylanisolvens DSM 23964 has no virulence potential. Since it also resists the action of gastric enzymes and low-pH conditions, this strain is an interesting candidate for further investigation of its safety and potential health-promoting properties.
Topics: Anti-Bacterial Agents; Bacterial Typing Techniques; Bacteroides; Cluster Analysis; DNA, Bacterial; DNA, Ribosomal; Feces; Humans; Microbial Sensitivity Tests; Nucleic Acid Hybridization; Phylogeny; Plasmids; Probiotics; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Virulence Factors; beta-Lactamases
PubMed: 22101046
DOI: 10.1128/AEM.06641-11 -
The ISME Journal May 2023The gut microbiota makes important contributions to host immune system development and resistance to pathogen infections, especially during early life. However, studies...
The gut microbiota makes important contributions to host immune system development and resistance to pathogen infections, especially during early life. However, studies addressing the immunomodulatory functions of gut microbial individuals or populations are limited. In this study, we explore the systemic impact of the ileal microbiota on immune cell development and function of chickens and identify the members of the microbiota involved in immune system modulation. We initially used a time-series design with six time points to prove that ileal microbiota at different succession stages is intimately connected to immune cell maturation. Antibiotics perturbed the microbiota succession and negatively affected immune development, whereas early exposure to the ileal commensal microbiota from more mature birds promoted immune cell development and facilitated pathogen elimination after Salmonella Typhimurium infection, illustrating that early colonization of gut microbiota is an important driver of immune development. Five bacterial strains, Blautia coccoides, Bacteroides xylanisolvens, Fournierella sp002159185, Romboutsia lituseburensis, and Megamonas funiformis, which are closely related to the immune system development of broiler chickens, were then screened out and validated for their immunomodulatory properties. Our results provide insight into poultry immune system-microbiota interactions and also establish a foundation for targeted immunological interventions aiming to combat infectious diseases and promote poultry health and production.
Topics: Animals; Chickens; Microbiota; Gastrointestinal Microbiome; Bacteria; Anti-Bacterial Agents
PubMed: 36849630
DOI: 10.1038/s41396-023-01387-z -
Microbiome Mar 2020The gut microbiota has the potential to influence the efficacy of cancer therapy. Here, we investigated the contribution of the intestinal microbiome on treatment...
The gut microbiota has the potential to influence the efficacy of cancer therapy. Here, we investigated the contribution of the intestinal microbiome on treatment outcomes in a heterogeneous cohort that included multiple cancer types to identify microbes with a global impact on immune response. Human gut metagenomic analysis revealed that responder patients had significantly higher microbial diversity and different microbiota compositions compared to non-responders. A machine-learning model was developed and validated in an independent cohort to predict treatment outcomes based on gut microbiota composition and functional repertoires of responders and non-responders. Specific species, Bacteroides ovatus and Bacteroides xylanisolvens, were positively correlated with treatment outcomes. Oral gavage of these responder bacteria significantly increased the efficacy of erlotinib and induced the expression of CXCL9 and IFN-γ in a murine lung cancer model. These data suggest a predictable impact of specific constituents of the microbiota on tumor growth and cancer treatment outcomes with implications for both prognosis and therapy.
Topics: Adult; Aged; Animals; Bacteria; Disease Models, Animal; Feces; Female; Gastrointestinal Microbiome; Genetic Variation; Humans; Longitudinal Studies; Lung Neoplasms; Male; Metagenomics; Mice; Mice, Inbred C57BL; Middle Aged; Neoplasms; Prognosis; Treatment Outcome
PubMed: 32138779
DOI: 10.1186/s40168-020-00811-2 -
Regulatory Toxicology and Pharmacology... Mar 2012We recently isolated and characterized the new strain Bacteroides xylanisolvens DSM 23964 and presented it as potential candidate for the first natural probiotic strain...
We recently isolated and characterized the new strain Bacteroides xylanisolvens DSM 23964 and presented it as potential candidate for the first natural probiotic strain of the genus Bacteroides. In order to evaluate the safety of this strain for use in food, the following standard toxicity assays were conducted with this strain in both viable and pasteurized form: in vitro bacterial reverse mutation assay, in vitro chromosomal aberration assay, and 90day subchronic repeated oral toxicity studies in mice. No mutagenic, clastogenic, or toxic effects were detected even at extremely high doses. In addition, no clinical, hematological, ophthalmological, or histopathological abnormality could be observed after necropsy at any of the doses tested. Hence, the NOAEL could be estimated to be greater than 2.3×10(11) CFUs, and 2.3×10(14) for pasteurized bacteria calculated as equivalent for an average 70kg human being. In addition, the absence of any in vivo pathogenic properties of viable B. xylanisolvens DSM 23964 cells was confirmed by means of an intraperitoneal abscess formation model in mice which also demonstrated that the bacteria are easily eradicated by the host's immune system. The obtained results support the assumed safety of B. xylanisolvens DSM 23964 for use in food.
Topics: Animals; Bacteroides; Female; Male; Mice; Mutagenicity Tests; No-Observed-Adverse-Effect Level; Probiotics; Rats; Risk Assessment
PubMed: 22085591
DOI: 10.1016/j.yrtph.2011.10.014 -
Frontiers in Immunology 2017Intestinal dysbiosis and metabolic endotoxemia have been associated with metabolic disorders, such as obesity, insulin resistance, and type 2 diabetes (T2D). The main...
Intestinal dysbiosis and metabolic endotoxemia have been associated with metabolic disorders, such as obesity, insulin resistance, and type 2 diabetes (T2D). The main goal of the present study was to evaluate the intestinal dysbiosis in Brazilian T2D patients and correlate these data with inflammatory cytokines and lipopolysaccharides (LPS) plasma concentrations. This study was approved by the Ethics Committees from Barretos Cancer Hospital and all individuals signed the informed consent form. Stool samples were required for DNA extraction, and the V3/V4 regions of bacterial 16S were sequenced using an Illumina platform. Peripheral blood was used to quantify inflammatory cytokines and plasma LPS concentrations, by CBA flex and ELISA, respectively. Statistical analyses were performed using Mann-Whitney and Spearman's tests. Analysis of variance, diversity indexes, and analysis of alpha- and beta-diversity were conducted using an annotated Operational Taxonomic Unit table. This study included 20 patients and 22 controls. We observed significant differences ( < 0.01) in the microbiota composition (beta-diversity) between patients and controls, suggesting intestinal dysbiosis in Brazilian T2D patients. The prevalent species found in patients' feces were the Gram-negatives , and . The proinflammatory interleukin-6 (IL-6) was significantly increased ( < 0.05) in patients' plasma and LPS levels were decreased. We find correlations between the proinflammatory interferon-gamma with Gram-negatives and species, and a positive correlation between the LPS levels and reads. The and species were associated with insulin resistance in previous studies. In this study, we suggested that the prevalence of Gram-negative species in the gut and the increased plasma IL-6 in patients could be linked to low-grade inflammation and insulin resistance. In conclusion, the and species could represent an intestinal microbiota signature, associated with T2D development. Furthermore, the identification of these Gram-negative bacteria, and the detection of inflammatory markers, such as increased IL-6, could be used as diabetes predictive markers in overweight, obese and in genetically predisposed individuals to develop T2D.
PubMed: 28966614
DOI: 10.3389/fimmu.2017.01107 -
MSystems Apr 2024The microbial utilization of dietary carbohydrates is closely linked to the pivotal role of the gut microbiome in human health. Inherent to the modulation of complex...
UNLABELLED
The microbial utilization of dietary carbohydrates is closely linked to the pivotal role of the gut microbiome in human health. Inherent to the modulation of complex microbial communities, a prebiotic implies the selective utilization of a specific substrate, relying on the metabolic capacities of targeted microbes. In this study, we investigated the metabolic capacities of 17 commensal bacteria of the human gut microbiome toward dietary carbohydrates with prebiotic potential. First, experiments allowed the classification of bacterial growth and fermentation profiles in response to various carbon sources, including agave inulin, corn fiber, polydextrose, and citrus pectin. The influence of phylogenetic affiliation appeared to statistically outweigh carbon sources in determining the degree of carbohydrate utilization. Second, we narrowed our focus on six commensal bacteria representative of the and phyla to perform an untargeted high-resolution liquid chromatography-mass spectrometry metabolomic analysis: , , , , and exhibited distinct metabolomic profiles in response to different carbon sources. The relative abundance of bacterial metabolites was significantly influenced by dietary carbohydrates, with these effects being strain-specific and/or carbohydrate-specific. Particularly, the findings indicated an elevation in short-chain fatty acids and other metabolites, including succinate, gamma-aminobutyric acid, and nicotinic acid. These metabolites were associated with putative health benefits. Finally, an RNA-Seq transcriptomic approach provided deeper insights into the underlying mechanisms of carbohydrate metabolization. Restricting our focus on four commensal bacteria, including , and , carbon sources did significantly modulate the level of bacterial genes related to the enzymatic machinery involved in the metabolization of dietary carbohydrates. This study provides a holistic view of the molecular strategies induced during the dynamic interplay between dietary carbohydrates with prebiotic potential and gut commensal bacteria.
IMPORTANCE
This study explores at a molecular level the interactions between commensal health-relevant bacteria and dietary carbohydrates holding prebiotic potential. We showed that prebiotic breakdown involves the specific activation of gene expression related to carbohydrate metabolism. We also identified metabolites produced by each bacteria that are potentially related to our digestive health. The characterization of the functional activities of health-relevant bacteria toward prebiotic substances can yield a better application of prebiotics in clinical interventions and personalized nutrition. Overall, this study highlights the importance of identifying the impact of prebiotics at a low resolution of the gut microbiota to characterize the activities of targeted bacteria that can play a crucial role in our health.
Topics: Humans; Prebiotics; Dietary Carbohydrates; Phylogeny; Bacteria; Carbon
PubMed: 38441031
DOI: 10.1128/msystems.01401-23 -
Marine Drugs Mar 2017Carrageenan, agarose, and alginate are algae-derived undigested polysaccharides that have been used as food additives for hundreds of years. Fermentation of dietary...
Carrageenan, agarose, and alginate are algae-derived undigested polysaccharides that have been used as food additives for hundreds of years. Fermentation of dietary carbohydrates of our food in the lower gut of humans is a critical process for the function and integrity of both the bacterial community and host cells. However, little is known about the fermentation of these three kinds of seaweed carbohydrates by human gut microbiota. Here, the degradation characteristics of carrageenan, agarose, alginate, and their oligosaccharides, by , , and , isolated from human gut microbiota, are studied.
Topics: Alginates; Aquatic Organisms; Bacteroidetes; Carrageenan; Fermentation; Gastrointestinal Microbiome; Glucuronic Acid; Hexuronic Acids; Humans; Microbiota; Oligosaccharides; Polysaccharides; Seaweed; Sepharose
PubMed: 28338633
DOI: 10.3390/md15040092 -
Journal of the American Chemical Society Jan 2017Inhibitor design incorporating features of the reaction coordinate and transition-state structure has emerged as a powerful approach for the development of enzyme...
Inhibitor design incorporating features of the reaction coordinate and transition-state structure has emerged as a powerful approach for the development of enzyme inhibitors. Such inhibitors find use as mechanistic probes, chemical biology tools, and therapeutics. Endo-α-1,2-mannosidases and endo-α-1,2-mannanases, members of glycoside hydrolase family 99 (GH99), are interesting targets for inhibitor development as they play key roles in N-glycan maturation and microbiotal yeast mannan degradation, respectively. These enzymes are proposed to act via a 1,2-anhydrosugar "epoxide" mechanism that proceeds through an unusual conformational itinerary. Here, we explore how shape and charge contribute to binding of diverse inhibitors of these enzymes. We report the synthesis of neutral dideoxy, glucal and cyclohexenyl disaccharide inhibitors, their binding to GH99 endo-α-1,2-mannanases, and their structural analysis by X-ray crystallography. Quantum mechanical calculations of the free energy landscapes reveal how the neutral inhibitors provide shape but not charge mimicry of the proposed intermediate and transition state structures. Building upon the knowledge of shape and charge contributions to inhibition of family GH99 enzymes, we design and synthesize α-Man-1,3-noeuromycin, which is revealed to be the most potent inhibitor (K 13 nM for Bacteroides xylanisolvens GH99 enzyme) of these enzymes yet reported. This work reveals how shape and charge mimicry of transition state features can enable the rational design of potent inhibitors.
Topics: Carbohydrate Conformation; Crystallography, X-Ray; Glucosamine; Glycoside Hydrolase Inhibitors; Mannosidases; Models, Molecular
PubMed: 27992199
DOI: 10.1021/jacs.6b10075 -
BMC Genomics Jun 2016
PubMed: 27267263
DOI: 10.1186/s12864-016-2758-3