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Toxins Feb 2022Chronic kidney disease (CKD) is predominant in 10% of the world's adult population, and is increasingly considered a silent epidemic. Gut microbiota plays an essential... (Review)
Review
Chronic kidney disease (CKD) is predominant in 10% of the world's adult population, and is increasingly considered a silent epidemic. Gut microbiota plays an essential role in maintaining host energy homeostasis and gut epithelial integrity. Alterations in gut microbiota composition, functions and, specifically, production of metabolites causing uremic toxicity are often associated with CKD onset and progression. Here, we present the latest omics (transcriptomics, proteomics and metabolomics) studies that explore the connection between CKD and gut microbiome. A review of the available literature using PubMed was performed using the keywords "microb*", "kidney", "proteom", "metabolom" and "transcript" for the last 10 years, yielding a total of 155 publications. Following selection of the relevant studies (focusing on microbiome in CKD), a predominance of metabolomics ( = 12) over transcriptomics ( = 1) and proteomics ( = 6) analyses was observed. A consensus arises supporting the idea that the uremic toxins produced in the gut cause oxidative stress, inflammation and fibrosis in the kidney leading to CKD. Collectively, findings include an observed enrichment of and spp., and a depletion in and spp. occurring in CKD models. Bacterial species involved in butyrate production, indole synthesis and mucin degradation were also related to CKD. Consequently, strong links between CKD and gut microbial dysbiosis suggest potential therapeutic strategies to prevent CKD progression and portray the gut as a promising therapeutic target.
Topics: Adult; Dysbiosis; Female; Gastrointestinal Microbiome; Humans; Kidney; Male; Microbiota; Renal Insufficiency, Chronic; Uremic Toxins
PubMed: 35324673
DOI: 10.3390/toxins14030176 -
Biomolecular NMR Assignments Oct 2022To fully utilize carbohydrates from seaweed biomass, the degradation of the family of polysaccharides known as alginates must be understood. A step in the degradation of...
To fully utilize carbohydrates from seaweed biomass, the degradation of the family of polysaccharides known as alginates must be understood. A step in the degradation of alginate is the conversion of 4,5-unsaturated monouronates to 4-deoxy-L-erythro-5-hexoseulose catalysed by the enzyme KdgF. In this study BeKdgF from Bacteroides eggerthii from the human gut microbiota has been produced isotopically labelled in Escherichia coli. Here the H, C, and N NMR chemical shift assignment for BeKdgF is reported.
Topics: Alginates; Bacteroides; Escherichia coli; Humans; Nuclear Magnetic Resonance, Biomolecular; Polysaccharides
PubMed: 36042150
DOI: 10.1007/s12104-022-10102-6 -
Brain, Behavior, and Immunity Oct 2023The correlation between human gut microbiota and psychiatric diseases has long been recognized. Based on the heritability of the microbiome, genome-wide association... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The correlation between human gut microbiota and psychiatric diseases has long been recognized. Based on the heritability of the microbiome, genome-wide association studies on human genome and gut microbiome (mbGWAS) have revealed important host-microbiome interactions. However, establishing causal relationships between specific gut microbiome features and psychological conditions remains challenging due to insufficient sample sizes of previous studies of mbGWAS.
METHODS
Cross-cohort meta-analysis (via METAL) and multi-trait analysis (via MTAG) were used to enhance the statistical power of mbGWAS for identifying genetic variants and genes. Using two large mbGWAS studies (7,738 and 5,959 participants respectively) and12 disease-specific studies from the Psychiatric Genomics Consortium (PGC), we performed bidirectional two-sample mendelian randomization (MR) analyses between microbial features and psychiatric diseases (up to 500,199 individuals). Additionally, we conducted downstream gene- and gene-set-based analyses to investigate the shared biology linking gut microbiota and psychiatric diseases.
RESULTS
METAL and MTAG conducted in mbGWAS could boost power for gene prioritization and MR analysis. Increases in the number of lead SNPs and mapped genes were witnessed in 13/15 species and 5/10 genera after using METAL, and MTAG analysis gained an increase in sample size equivalent to expanding the original samples from 7% to 63%. Following METAL use, we identified a positive association between Bacteroides faecis and ADHD (OR, 1.09; 95 %CI, 1.02-1.16; P = 0.008). Bacteroides eggerthii and Bacteroides thetaiotaomicron were observed to be positively associated with PTSD (OR, 1.11; 95 %CI, 1.03-1.20; P = 0.007; OR, 1.11; 95 %CI, 1.01-1.23; P = 0.03). These findings remained stable across statistical models and sensitivity analyses. No genetic liabilities to psychiatric diseases may alter the abundance of gut microorganisms.Using biological annotation, we identified that those genes contributing to microbiomes (e.g., GRIN2A and RBFOX1) are expressed and enriched in human brain tissues.
CONCLUSIONS
Our statistical genetics strategy helps to enhance the power of mbGWAS, and our genetic findings offer new insights into biological pleiotropy and causal relationship between microbiota and psychiatric diseases.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Microbiota; Mental Disorders
PubMed: 37557965
DOI: 10.1016/j.bbi.2023.08.003 -
Preparative Biochemistry & Biotechnology 2020Heparinase I (Hep I) specifically degrades heparin to oligosaccharide or unsaturated disaccharide and has been widely used in preparation of low molecular weight heparin...
Heparinase I (Hep I) specifically degrades heparin to oligosaccharide or unsaturated disaccharide and has been widely used in preparation of low molecular weight heparin (LMWH). In this work, a novel Hep I from VPI T5-42B-1 was cloned and overexpressed in BL21 (DE3). The enzyme has specific activity of 480 IU·mg at the optimal temperature and pH of 30 °C and pH 7.5, and the and V were 3.6 mg·mL and 647.93 U·mg, respectively. The Hep I has good stability with t values of 350 and 60 min at 30 and 37 °C, respectively. And it showed a residual relative activity of 70.8% after 21 days incubation at 4 °C. Substrate docking study revealed that Lys99, Arg101, Gln241, Lys270, Asn275, and Lys292 were mainly involved in the substrate binding of Hep I. The shorter hydrogen bonds formed between heparin and these residues suggested the higher specific activity of BeHep I. And the minimum conformational entropy value of 756 J·K provides an evidence for the improved stability of this enzyme. This Hep I could be of interest in the industrial preparation of LMWH for its high specific activity and good stability.
Topics: Amino Acid Sequence; Bacterial Proteins; Bacteroides; Cloning, Molecular; Enzyme Assays; Escherichia coli; Gene Expression; Heparin; Heparin Lyase; Molecular Docking Simulation; Pedobacter; Protein Binding; Sequence Alignment
PubMed: 31900079
DOI: 10.1080/10826068.2019.1709977 -
Scientific Reports Sep 2021Bacteroidetes are efficient degraders of complex carbohydrates, much thanks to their use of polysaccharide utilization loci (PULs). An integral part of PULs are highly...
Bacteroidetes are efficient degraders of complex carbohydrates, much thanks to their use of polysaccharide utilization loci (PULs). An integral part of PULs are highly specialized carbohydrate-active enzymes, sometimes composed of multiple linked domains with discrete functions-multicatalytic enzymes. We present the biochemical characterization of a multicatalytic enzyme from a large PUL encoded by the gut bacterium Bacteroides eggerthii. The enzyme, BeCE15A-Rex8A, has a rare and novel architecture, with an N-terminal carbohydrate esterase family 15 (CE15) domain and a C-terminal glycoside hydrolase family 8 (GH8) domain. The CE15 domain was identified as a glucuronoyl esterase (GE), though with relatively poor activity on GE model substrates, attributed to key amino acid substitutions in the active site compared to previously studied GEs. The GH8 domain was shown to be a reducing-end xylose-releasing exo-oligoxylanase (Rex), based on having activity on xylooligosaccharides but not on longer xylan chains. The full-length BeCE15A-Rex8A enzyme and the Rex domain were capable of boosting the activity of a commercially available GH11 xylanase on corn cob biomass. Our research adds to the understanding of multicatalytic enzyme architectures and showcases the potential of discovering novel and atypical carbohydrate-active enzymes from mining PULs.
Topics: Bacterial Proteins; Bacteroides; Glycoside Hydrolases; Humans; Polysaccharides
PubMed: 34480044
DOI: 10.1038/s41598-021-96659-z -
PloS One 2016Dysbiosis is a hallmark of inflammatory bowel disease (IBD), but it is unclear which specific intestinal bacteria predispose to and which protect from IBD and how they...
Dysbiosis is a hallmark of inflammatory bowel disease (IBD), but it is unclear which specific intestinal bacteria predispose to and which protect from IBD and how they are regulated. Peptidoglycan recognition proteins (Pglyrps) are antibacterial, participate in maintaining intestinal microflora, and modulate inflammatory responses. Mice deficient in any one of the four Pglyrp genes are more sensitive to dextran sulfate sodium (DSS)-induced colitis, and stools from Pglyrp-deficient mice transferred to wild type (WT) germ-free mice predispose them to much more severe colitis than stools from WT mice. However, the identities of these Pglyrp-regulated bacteria that predispose Pglyrp-deficient mice to colitis or protect WT mice from colitis are not known. Here we identified significant changes in β-diversity of stool bacteria in Pglyrp-deficient mice compared with WT mice. The most consistent changes in microbiome in all Pglyrp-deficient mice were in Bacteroidales, from which we selected four species, two with increased abundance (Prevotella falsenii and Parabacteroides distasonis) and two with decreased abundance (Bacteroides eggerthii and Alistipes finegoldii). We then gavaged WT mice with stock type strains of these species to test the hypothesis that they predispose to or protect from DSS-induced colitis. P. falsenii, P. distasonis, and B. eggerthii all enhanced DSS-induced colitis in both WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora. By contrast, A. finegoldii (which is the most abundant species in WT mice) attenuated DSS-induced colitis both in WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora, similar to the colitis protective effect of the entire normal microflora. These results identify P. falsenii, P. distasonis, and B. eggerthii as colitis-promoting species and A. finegoldii as colitis-protective species.
Topics: Animals; Bacteroidetes; Carrier Proteins; Colitis; Cytokines; Dextran Sulfate; Disease Susceptibility; Feces; Female; Gastrointestinal Microbiome; Immunity, Innate; Intestines; Mice; Mice, Inbred BALB C; Mice, Knockout; Prevotella; Probiotics; Ribotyping
PubMed: 26727498
DOI: 10.1371/journal.pone.0146162 -
The Journal of Allergy and Clinical... Dec 2023The composition of the gut microbiome has been associated with development of atopic conditions such as food allergy (FA) and asthma. African American or Black children...
BACKGROUND
The composition of the gut microbiome has been associated with development of atopic conditions such as food allergy (FA) and asthma. African American or Black children with FA have higher rate of asthma compared to their White counterparts.
OBJECTIVE
We sought to investigate whether the diversity and relative abundance (RA) of gut microbiota is different between children with FA from different racial backgrounds living in the same cities. Furthermore, we aimed to understand whether the difference in the gut microbiota is associated with asthma in children with FA.
METHODS
We analyzed and compared the stool microbiome of a cohort of Black and White children with FA by shotgun genomic sequencing.
RESULTS
A total of 152 children with IgE-mediated FA enrolled onto FORWARD (Food Allergy Outcomes Related to White and African American Racial Differences); 30 Black and 122 White children were included. The RA of several bacteria was associated with race and asthma. Most notably the RA of Bacteroides thetaiotaomicron, Chlamydia thrachomatis, Parabacteroides goldsteinii, and Bacteroides eggerthii were significantly higher, while the RA of Bifidobacterium sp CAG:754, Parabacterium johnsonii, Bacteroides intestinalis, and Bifidobacterium breve were significantly lower in stool samples of Black children compared to White children. Asthma was associated with lower RA of B breve, Bifidobacterium catenulatum, Prevotella copri, Veilloella sp CAG:933, and Bacteroides plebius, and higher RA of 3 Bacteroides species.
CONCLUSIONS
The observed variations in the gut microbiota of Black and White children such as differences in the Bacteroides and Bifidobacterium species along with their association to history of asthma in our cohort is indicative of their potential role in the higher rate of asthma observed among Black children with FA.
Topics: Child; Humans; Gastrointestinal Microbiome; Food Hypersensitivity; Microbiota; Feces; Asthma
PubMed: 37714436
DOI: 10.1016/j.jaci.2023.07.024 -
International Journal of Medical... 2021Although associations between low protein diet (LPD) and changes of gut microbiota have been reported; however, systematic discernment of the effects of LPD on... (Meta-Analysis)
Meta-Analysis
Although associations between low protein diet (LPD) and changes of gut microbiota have been reported; however, systematic discernment of the effects of LPD on diet-microbiome-host interaction in patients with chronic kidney disease (CKD) is lacking. We searched PUBMED and EMBASE for articles published on changes of gut microbiota associated with implementation of LPD in CKD patients until July 2021. Independent researchers extracted data and assessed risks of bias. We conducted meta-analyses of combine p-value, mean differences and random effects for gut microbiota and related metabolites. Study heterogeneity was measured by Tau and I statistic. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Five articles met inclusion criteria. The meta-analyses of gut microbiota exhibited enrichments of Lactobacillaceae (meta-= 0.010), Bacteroidaceae (meta-= 0.048) and Streptococcus anginosus (meta-< 0.001), but revealed depletion of Bacteroides eggerthii (=0.017) and Roseburia faecis (meta-=0.019) in LPD patients compared to patients undergoing normal protein diet. The serum IS levels (mean difference: 0.68 ug/mL, 95% CI: -8.38-9.68, = 0.89) and pCS levels (mean difference: -3.85 ug/mL, 95% CI: -15.49-7.78, < 0.52) did not change between groups. We did not find significant differences on renal function associated with change of microbiota between groups (eGFR, mean difference: -7.21 mL/min/1.73 m, 95% CI: -33.2-18.79, = 0.59; blood urea nitrogen, mean difference: -6.8 mg/dL, 95% CI: -46.42-32.82, = 0.74). Other clinical (sodium, potassium, phosphate, albumin, fasting sugar, uric acid, total cholesterol, triglycerides, C-reactive protein and hemoglobin) and anthropometric estimates (body mass index, systolic blood pressure and diastolic blood pressure) did not differ between the two groups. This systematic review and meta-analysis suggested that the effects of LPD on the microbiota were observed predominantly at the families and species levels but minimal on microbial diversity or richness. In the absence of global compositional microbiota shifts, the species-level changes appear insufficient to alter metabolic or clinical outputs.
Topics: Diet, Protein-Restricted; Dysbiosis; Gastrointestinal Microbiome; Humans; Internationality; Renal Insufficiency, Chronic
PubMed: 34790060
DOI: 10.7150/ijms.66451 -
Chembiochem : a European Journal of... May 2015Bacterial heparinases that cleave heparan sulfate (HS) and heparin are widely used to generate low-molecular-weight heparins (LMWHs) and to structurally and functionally...
Bacterial heparinases that cleave heparan sulfate (HS) and heparin are widely used to generate low-molecular-weight heparins (LMWHs) and to structurally and functionally characterise heparin and HS biomolecules. We provide novel insights into the substrate specificity of heparinase II from two different bacteria: Pedobacter heparinus (formerly Flavobacterium heparinum) and Bacteroides eggerthii. The activity towards various well-defined HS oligosaccharides was investigated by (1) H NMR spectroscopy; this revealed distinct specificities for the two heparinases. Heparinase II from P. heparinus appears to be more active and displays a broader substrate specificity than B. eggerthii heparinase II. Furthermore, HS di- and tetrasaccharides inhibited B. eggerthii heparinase II activity. A better understanding of heparinase substrate specificity will contribute to the production of homogenous LMWHs, provide better characterisation of heparin and HS and assist therapeutic applications.
Topics: Antithrombins; Bacteroidaceae; Binding Sites; Enzyme Inhibitors; Heparitin Sulfate; Pedobacter; Polysaccharide-Lyases; Substrate Specificity
PubMed: 25907974
DOI: 10.1002/cbic.201500081 -
Novel Thermostable Heparinase Based on the Genome of Bacteroides Isolated from Human Gut Microbiota.Foods (Basel, Switzerland) May 2022Among the nutrients available to the human gut microbiota, the complex carbohydrates and glycosaminoglycans are important sources of carbon for some of the species of...
Among the nutrients available to the human gut microbiota, the complex carbohydrates and glycosaminoglycans are important sources of carbon for some of the species of human gut microbiota. Glycosaminoglycan (heparin) from the host is a highly preferred carbohydrate for . To explore how gut microbiota can effectively use heparin as a carbon source for growth, we conducted a screening of the Carbohydrate-Active enzymes (CAZymes) database for lytic enzymes of the PL13 family and Research Center of Food Biotechnology at School of Food Science and Technology of Jiangnan University database of to identify novel glycosaminoglycan-degrading bacterial strains. Four species (, , , and ) that degraded heparin were selected for further studies. Analysis of the polysaccharide utilization sites of the four strains revealed that all of them harbored enzyme encoding genes of the PL13 family. Functional analysis revealed the activity of CAZymes in a medium containing heparin as the sole carbon source, suggesting their potential to degrade heparin and support growth. The four enzymes were heterologous expressed, and their enzymatic properties, kinetics, and thermal stability were determined. The lytic enzyme of had high enzymatic activity and thermal stability. The features that cause this high thermal stability were elucidated based on an examination of the three-dimensional structure of the protein. Our findings provide an important theoretical basis for the application of glycosaminoglycans and glycosaminoglycan-degrading enzymes in the medical and biotechnology industries, and an important scientific basis for precision nutrition and medical intervention studies using gut microbiota or enzymes as targets.
PubMed: 35627031
DOI: 10.3390/foods11101462