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AIMS/HYPOTHESIS: The use of oral glucose-lowering drugs, particularly those designed to target the gut ecosystem, is often observed in association with altered gut microbial composition or functional capacity in individuals with type 2 diabetes. The gut microbiota, in turn, plays crucial roles in the modulation of drug efficacy. We aimed to assess the impacts of acarbose and vildagliptin on human gut microbiota and the relationships between pre-treatment gut microbiota and therapeutic responses. METHODS: This was a randomised, open-labelled, two-arm trial in treatment-naive type 2 diabetes patients conducted in Beijing between December 2016 and December 2017. One hundred participants with overweight/obesity and newly diagnosed type 2 diabetes were recruited from the Pinggu Hospital and randomly assigned to the acarbose (n=50) or vildagliptin (n=50) group using sealed envelopes. The treatment period was 6 months. Blood, faecal samples and visceral fat data from computed tomography images were collected before and after treatments to measure therapeutic outcomes and gut microbiota. Metagenomic datasets from a previous type 2 diabetes cohort receiving acarbose or glipizide for 3 months were downloaded and processed. Statistical analyses were applied to identify the treatment-related changes in clinical variables, gut microbiota and associations. RESULTS: Ninety-two participants were analysed. After 6 months of acarbose (n=44) or vildagliptin (n=48) monotherapy, both groups achieved significant reductions in HbA1c (from 60 to 46 mmol/mol [from 7.65% to 6.40%] in the acarbose group and from 59 to 44 mmol/mol [from 7.55% to 6.20%] in the vildagliptin group) and visceral fat areas (all adjusted p values for pre-post comparisons <0.05). Both arms showed drug-specific and shared changes in relative abundances of multiple gut microbial species and pathways, especially the common reductions in Bacteroidetes species. Three months and 6 months of acarbose-induced changes in microbial composition were highly similar in type 2 diabetes patients from the two independent studies. Vildagliptin treatment significantly enhanced fasting active glucagon-like peptide-1 (GLP-1) levels. Baseline gut microbiota, rather than baseline GLP-1 levels, were strongly associated with GLP-1 response to vildagliptin, and to a lesser extent with GLP-1 response to acarbose. CONCLUSIONS/INTERPRETATION: This study reveals common microbial responses in type 2 diabetes patients treated with two glucose-lowering drugs targeting the gut differently and acceptable performance of baseline gut microbiota in classifying individuals with different GLP-1 responses to vildagliptin. Our findings highlight bidirectional interactions between gut microbiota and glucose-lowering drugs. TRIAL REGISTRATION: ClinicalTrials.gov NCT02999841 FUNDING: National Key Research and Development Project: 2016YFC1304901.
Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Acarbose/uso terapêutico , Glicemia/metabolismo , China , Ecossistema , Trato Gastrointestinal/metabolismo , Glipizida/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Glucose , Humanos , Hipoglicemiantes/farmacologia , Pesquisa , Vildagliptina/uso terapêuticoRESUMO
Emerging experimental evidence indicates that toxicant-induced alterations in gut microbiota composition and activity may affect host homeostasis. However, data from human studies are scarce; to our knowledge, no previous studies have quantified the association of lifetime exposure to environmental chemicals, across multiple time points, with the composition of the adult gut microbiome. Here we studied 124 individuals born in the Faroe Islands in 1986-1987 who were followed approximately every seven years from birth through age 28 years. Organochlorine compounds, including polychlorinated biphenyls (PCBs) and pesticides, perfluoroalkyl substances (PFAS), and mercury (Hg), were measured in cord blood and longitudinally in participants' blood. At age 28, the gut microbiome was assessed using shotgun metagenomic sequencing. Historical contaminant exposures had little direct effect on the adult gut microbiome, while a small number of fastidious anaerobes were weakly linked to recent PFAS/PFOS exposures at age 28. In this cohort, our findings suggest no lasting effects of early life exposures on adult gut microbial composition, but proximal exposures may contribute to gut microbiome alterations. The methods developed and used for this investigation may help in future identification of small but lasting impacts of environmental toxicant exposure on the gut microbiome.
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Poluentes Ambientais , Fluorocarbonos , Microbioma Gastrointestinal , Hidrocarbonetos Clorados , Mercúrio , Bifenilos Policlorados , Adulto , Humanos , Poluentes Ambientais/análise , Bifenilos Policlorados/análise , Substâncias PerigosasRESUMO
A bacterial strain, designated N-1-3-6T, was isolated from a soil sample collected from the arctic regions. The cells were short rods, Gram-stain-negative, catalase- and oxidase-positive. Growth was observed with 0-12â% (w/v) NaCl, with optimal growth at 0.5-2â%, and at pH 6.0-9.0, with optimum of pH 7.0, and a growth temperature of 10-45 °C, with an optimum of 28-37 °C. Phylogenetic analysis based on the 16S rRNA gene placed N-1-3-6T in the genus Sinomicrobium with the closest relative being Sinomicrobium pectinilyticum 5DNS001T, exhibiting 95.3â% 16S rRNA pairwise similarity. A polyphasic taxonomic study, including phenotypic, chemotaxonomic and molecular analyses, was performed to clarify its taxonomic position. N-1-3-6T contained MK-6 as the predominant menaquinone. Polar lipids consisted of phosphatidylethanolamine and several unidentified aminolipids, phospholipids and lipids. The principal fatty acids (>10â%) were iso-C15â:â0 (26.9â%), summed feature 3 [C16â:âω7c/ω6c (17.2â%)] and iso-C17â:â0 3-OH (14.7â%). The DNA G+C content of N-1-3-6T was 47.7 mol%. On the basis of its phenotypic and genotypic properties, strain N-1-3-6T should be classified as representing a novel species of the genus Sinomicrobium, for which the name Sinomicrobium soli sp. nov. is proposed, with the type strain N-1-3-6T (=MCCC 1A06047T=KCTC 52339T).
Assuntos
Filogenia , Microbiologia do Solo , Regiões Árticas , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Flavobacteriaceae , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMO
The administration of oral antidiabetic drugs (OADs) to patients with type 2 diabetes elicits distinct and shared changes in the gut microbiota, with acarbose and berberine exhibiting greater impacts on the gut microbiota than metformin, vildagliptin, and glipizide. The baseline gut microbiota strongly associates with treatment responses of OADs.
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The incidence of young-onset colorectal cancer (yCRC) has been increasing in recent decades, but little is known about the gut microbiome of these patients. Most studies have focused on old-onset CRC (oCRC), and it remains unclear whether CRC signatures derived from old patients are valid in young patients. To address this, we assembled the largest yCRC gut metagenomes to date from two independent cohorts and found that the CRC microbiome had limited association with age across adulthood. Differential analysis revealed that well-known CRC-associated taxa, such as Clostridium symbiosum, Peptostreptococcus stomatis, Parvimonas micra and Hungatella hathewayi were significantly enriched (false discovery rate <0.05) in both old- and young-onset patients. Similar strain-level patterns of Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli were observed for oCRC and yCRC. Almost all oCRC-associated metagenomic pathways had directionally concordant changes in young patients. Importantly, CRC-associated virulence factors (fadA, bft) were enriched in both oCRC and yCRC compared to their respective controls. Moreover, the microbiome-based classification model had similar predication accuracy for CRC status in old- and young-onset patients, underscoring the consistency of microbial signatures across different age groups.
Assuntos
Idade de Início , Neoplasias Colorretais , Microbioma Gastrointestinal , Humanos , Neoplasias Colorretais/microbiologia , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Metagenoma , Metagenômica/métodos , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Adulto Jovem , Fezes/microbiologia , Estudos de CoortesRESUMO
CONTEXT: Cushing syndrome (CS) is a severe endocrine disease characterized by excessive secretion of cortisol with multiple metabolic disorders. While gut microbial dysbiosis plays a vital role in metabolic disorders, the role of gut microbiota in CS remains unclear. OBJECTIVE: The objective of this work is to examine the alteration of gut microbiota in patients with CS. METHODS: We performed shotgun metagenomic sequencing of fecal samples from 78 patients with CS and 78 healthy controls matched for age and body mass index. Furthermore, we verify the cortisol degradation capacity of Ruminococcus gnavus in vitro and identify the potential metabolite by LC-MC/MS. RESULTS: We observed significant differences in microbial composition between CS and controls in both sexes, with CS showing reduced Bacteroidetes (Bacteroides vulgatus) and elevated Firmicutes (Erysipelotrichaceae_bacterium_6_1_45) and Proteobacteria (Enterobacter cloacae). Despite distinct causes of hypercortisolism in ACTH-dependent and ACTH-independent CS, we found no significant differences in metabolic profiles or gut microbiota between the 2 subgroups. Furthermore, we identified a group of gut species, including R. gnavus, that were positively correlated with cortisol levels in CS. These bacteria were found to harbor cortisol-degrading desAB genes and were consistently enriched in CS. Moreover, we demonstrated the efficient capacity of R. gnavus to degrade cortisol to 11-oxygenated androgens in vitro. CONCLUSION: This study provides evidence of gut microbial dysbiosis in patients with CS and identifies a group of CS-enriched bacteria capable of degrading cortisol. These findings highlight the potential role of gut microbiota in regulating host steroid hormone levels, and consequently host health.
Assuntos
Síndrome de Cushing , Disbiose , Fezes , Microbioma Gastrointestinal , Hidrocortisona , Humanos , Disbiose/microbiologia , Disbiose/metabolismo , Masculino , Feminino , Microbioma Gastrointestinal/fisiologia , Síndrome de Cushing/microbiologia , Síndrome de Cushing/metabolismo , Hidrocortisona/metabolismo , Pessoa de Meia-Idade , Adulto , Fezes/microbiologia , Estudos de Casos e Controles , Clostridiales/isolamento & purificação , Clostridiales/metabolismoRESUMO
Insight into associations between the gut microbiome with metabolism and aging is crucial for tailoring interventions to promote healthy longevity. In a discovery cohort of 10,207 individuals aged 40-93 years, we used 21 metabolic parameters to classify individuals into five clusters, termed metabolic multimorbidity clusters (MCs), that represent different metabolic subphenotypes. Compared to the cluster classified as metabolically healthy (MC1), clusters classified as 'obesity-related mixed' (MC4) and 'hyperglycemia' (MC5) exhibited an increased 11.1-year cardiovascular disease (CVD) risk by 75% (multivariable-adjusted hazard ratio (HR): 1.75, 95% confidence interval (CI): 1.43-2.14) and by 117% (2.17, 1.72-2.74), respectively. These associations were replicated in a second cohort of 9,061 individuals with a 10.0-year follow-up. Based on analysis of 4,491 shotgun fecal metagenomes from the discovery cohort, we found that gut microbial composition was associated with both MCs and age. Next, using 55 age-specific microbial species to capture biological age, we developed a gut microbial age (MA) metric, which was validated in four external cohorts comprising 4,425 metagenomic samples. Among individuals aged 60 years or older, the increased CVD risk associated with MC4 or MC5, as compared to MC1, MC2 or MC3, was exacerbated in individuals with high MA but diminished in individuals with low MA, independent of age, sex and other lifestyle and dietary factors. This pattern, in which younger MA appears to counteract the CVD risk attributable to metabolic dysfunction, implies a modulating role of MA in cardiovascular health for metabolically unhealthy older people.
Assuntos
Doenças Cardiovasculares , Microbioma Gastrointestinal , Humanos , Pessoa de Meia-Idade , Idoso , Doenças Cardiovasculares/microbiologia , Doenças Cardiovasculares/epidemiologia , Feminino , Masculino , Adulto , Idoso de 80 Anos ou mais , Envelhecimento , Fatores de Risco , Fezes/microbiologia , Estudos de Coortes , Fatores Etários , MetagenomaRESUMO
Numerous studies have reported critical roles for the gut microbiota in obesity. However, the specific microbes that causally contribute to obesity and the underlying mechanisms remain undetermined. Here, we conducted shotgun metagenomic sequencing in a Chinese cohort of 631 obese subjects and 374 normal-weight controls and identified a Megamonas-dominated, enterotype-like cluster enriched in obese subjects. Among this cohort, the presence of Megamonas and polygenic risk exhibited an additive impact on obesity. Megamonas rupellensis possessed genes for myo-inositol degradation, as demonstrated in vitro and in vivo, and the addition of myo-inositol effectively inhibited fatty acid absorption in intestinal organoids. Furthermore, mice colonized with M. rupellensis or E. coli heterologously expressing the myo-inositol-degrading iolG gene exhibited enhanced intestinal lipid absorption, thereby leading to obesity. Altogether, our findings uncover roles for M. rupellensis as a myo-inositol degrader that enhances lipid absorption and obesity, suggesting potential strategies for future obesity management.
Assuntos
Microbioma Gastrointestinal , Inositol , Obesidade , Inositol/metabolismo , Obesidade/microbiologia , Obesidade/metabolismo , Animais , Humanos , Camundongos , Masculino , Metabolismo dos Lipídeos , Feminino , Absorção Intestinal , Camundongos Endogâmicos C57BL , Metagenômica , Pessoa de Meia-Idade , Adulto , Ácidos Graxos/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismoRESUMO
Background: Programmed death 1 (PD-1) and the ligand of PD-1 (PD-L1) are central targets for immune-checkpoint therapy (ICT) blocking immune evasion-related pathways elicited by tumor cells. A number of PD-1 inhibitors have been developed, but the efficacy of these inhibitors varies considerably and is typically below 50%. The efficacy of ICT has been shown to be dependent on the gut microbiota, and experiments using mouse models have even demonstrated that modulation of the gut microbiota may improve efficacy of ICT. Methods: We followed a Han Chinese cohort of 85 advanced non-small cell lung cancer (NSCLC) patients, who received anti-PD-1 antibodies. Tumor biopsies were collected before treatment initiation for whole exon sequencing and variant detection. Fecal samples collected biweekly during the period of anti-PD-1 antibody administration were used for metagenomic sequencing. We established gut microbiome abundance profiles for identification of significant associations between specific microbial taxa, potential functionality, and treatment responses. A prediction model based on random forest was trained using selected markers discriminating between the different response groups. Results: NSCLC patients treated with antibiotics exhibited the shortest survival time. Low level of tumor-mutation burden and high expression level of HLA-E significantly reduced progression-free survival. We identified metagenomic species and functional pathways that differed in abundance in relation to responses to ICT. Data on differential enrichment of taxa and predicted microbial functions in NSCLC patients responding or non-responding to ICT allowed the establishment of random forest algorithm-adopted models robustly predicting the probability of whether or not a given patient would benefit from ICT. Conclusions: Overall, our results identified links between gut microbial composition and immunotherapy efficacy in Chinese NSCLC patients indicating the potential for such analyses to predict outcome prior to ICT.
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Non-fasting lipidemia (nFL), mainly contributed by postprandial lipidemia (PL), has recently been recognized as an important cardiovascular disease (CVD) risk as fasting lipidemia (FL). PL serves as a common feature of dyslipidemia in Type 2 Diabetes (T2D), albeit effective therapies targeting on PL were limited. In this study, we aimed to evaluate whether the therapy combining probiotics (Prob) and berberine (BBR), a proven antidiabetic and hypolipidemic regimen via altering gut microbiome, could effectively reduce PL in T2D and to explore the underlying mechanism. Blood PL (120 min after taking 100 g standard carbohydrate meal) was examined in 365 participants with T2D from the Probiotics and BBR on the Efficacy and Change of Gut Microbiota in Patients with Newly Diagnosed Type 2 Diabetes (PREMOTE study), a random, placebo-controlled, and multicenter clinical trial. Prob+BBR was superior to BBR or Prob alone in improving postprandial total cholesterol (pTC) and low-density lipoprotein cholesterol (pLDLc) levels with decrement of multiple species of postprandial lipidomic metabolites after 3 months follow-up. This effect was linked to the changes of fecal Bifidobacterium breve level responding to BBR alone or Prob+BBR treatment. Four fadD genes encoding long-chain acyl-CoA synthetase were identified in the genome of this B. breve strain, and transcriptionally activated by BBR. In vitro BBR treatment further decreased the concentration of FFA in the culture medium of B. breve compared to vehicle. Thus, the activation of fadD by BBR could enhance FFA import and mobilization in B. breve and diliminish the intraluminal lipids for absorption to mediate the effect of Prob+BBR on PL. Our study confirmed that BBR and Prob (B. breve) could exert a synergistic hypolipidemic effect on PL, acting as a gut lipid sink to achieve better lipidemia and CVD risk control in T2D.
Assuntos
Berberina/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Probióticos/administração & dosagem , Adulto , Animais , Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/microbiologia , Método Duplo-Cego , Quimioterapia Combinada , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/microbiologia , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial/efeitos dos fármacosRESUMO
A taxonomic study was carried out on a novel strain, designated CK-I3-6(T), which was isolated from deep-sea sediment of the south-west Indian Ocean Ridge. Cells were Gram-reaction-negative, oxidase- and catalase-positive, rod-shaped and non-motile. Growth was observed at 4-38 °C and in 1-12â% (w/v) NaCl. Cells were able to degrade gelatin and oxidize thiosulfate but did not reduce nitrate. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CK-I3-6(T) belonged to the genus Citreicella with a sequence similarity of 97.3â% to Citreicella thiooxidans CHLG 1(T), while similarities with other taxa were <95.7â%. DNA-DNA hybridization showed that strain CK-I3-6(T) and C. thiooxidans CHLG 1(T) showed a low DNA-DNA relatedness (48±3â%). The principal fatty acids were C(16â:â0) (7.8â%), C(18â:â1)ω7c (66.6â%), summed feature 3 (C(16â:â1)ω6c and/or C(16â:â1)ω7c; 6.3â%) and C(19â:â0)ω8c cyclo (10.0â%). The chromosomal DNA G+C content was 67.5 mol%. On the basis of the combined genotypic and phenotypic data, strain CK-I3-6(T) represents a novel species of the genus Citreicella, for which the name Citreicella marina sp. nov. is proposed. The type strain is CK-I3-6(T) (â=âCCTCC AB 209064(T) â=âLMG 25230(T) â=âMCCC 1A03060(T)).
Assuntos
Sedimentos Geológicos/microbiologia , Rhodobacteraceae/classificação , Rhodobacteraceae/isolamento & purificação , Composição de Bases , Catalase/metabolismo , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Ácidos Graxos/análise , Gelatina/metabolismo , Oceano Índico , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Oxirredutases/metabolismo , Filogenia , RNA Ribossômico 16S/genética , Rhodobacteraceae/genética , Rhodobacteraceae/fisiologia , Análise de Sequência de DNA , Cloreto de Sódio/metabolismo , Temperatura , Tiossulfatos/metabolismoRESUMO
A taxonomic study was carried out on a novel bacterial strain, designated B108(T), which was isolated from a polycyclic aromatic hydrocarbon (PAH)-degrading consortium, enriched from deep-sea water of the Indian Ocean. The isolate was Gram-reaction-negative, rod-shaped and non-motile. Growth of strain B108(T) was observed in 1-15â% (w/v) NaCl and at 10-39 °C and it was unable to degrade Tween 80 or gelatin. 16S rRNA gene sequence comparisons showed that strain B108(T) was most closely related to Roseovarius halotolerans HJ50(T) (97.1â% sequence similarity), followed by Roseovarius pacificus 81-2(T) (96.6â%) and Roseovarius aestuarii SMK-122(T) (95.2â%); other species shared <95.0â% sequence similarity. DNA-DNA hybridization tests showed that strain B108(T) had a low DNA-DNA relatedness to R. halotolerans HJ50(T) and R. pacificus 81-2(T) (48±4â% and 44±5â%, respectively). The predominant fatty acids were C16:0, C16:0 2-OH, summed feature 8 (C18:1ω7c/ω6c) and C19:0ω8c cyclo, which accounted for 84.2â% of the total cellular fatty acids. The G+C content of the chromosomal DNA was 63.6 mol%. The major respiratory quinone was ubiquinone 10 (Q10). Phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and some unidentified compounds were detected. These characteristics were in good agreement with those of members of the genus Roseovarius. The pufLM gene was also detected. According to its morphology, physiology, fatty acid composition and phylogenetic position based on 16S rRNA sequence data, the novel strain most appropriately belongs to the genus Roseovarius but can be readily distinguished from known species of this genus. Therefore, strain B108(T) represents a novel species, of the genus Roseovarius, for which the name Roseovarius indicus sp. nov. is proposed. The type strain is B108(T) (â=â2PR52-14(T) â=âCCTCC AB 208233(T) â=âLMG 24622(T) â=âMCCC 1A01227(T)).
Assuntos
Rhodobacteraceae/classificação , Rhodobacteraceae/isolamento & purificação , Água do Mar/microbiologia , Proteínas de Bactérias/genética , Técnicas de Tipagem Bacteriana , Composição de Bases , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Ácidos Graxos/análise , Oceano Índico , Complexos de Proteínas Captadores de Luz/genética , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Fosfolipídeos/análise , Complexo de Proteínas do Centro de Reação Fotossintética/genética , Filogenia , Polissorbatos/metabolismo , Quinonas/análise , RNA Ribossômico 16S/genética , Rhodobacteraceae/genética , Rhodobacteraceae/fisiologia , Análise de Sequência de DNA , Cloreto de Sódio/metabolismo , TemperaturaRESUMO
A taxonomic study was carried out on a novel bacterial strain, designated W11-5(T), which was isolated from a pyrene-degrading consortium enriched from deep-sea sediment of the Pacific Ocean. The isolate was Gram-reaction-negative and oxidase- and catalase-positive. Growth was observed in 0.5-12 % (w/v) NaCl and at 10-42 °C. On the basis of 16S rRNA gene sequence analysis, strain W11-5(T) was shown to belong to the genus Alcanivorax with a close relation to A. dieselolei B-5(T) (93.9 % 16S rRNA sequence similarity), A. balearicus MACL04(T) (93.1 %), A. hongdengensis A-11-3(T) (93.1 %), A. borkumensis SK2(T) (93.0 %), A. venustensis ISO4(T) (93.0 %) and A. jadensis T9(T) (92.9 %). Similarities between the gyrB gene sequences of W11-5(T) and other species of the genus Alcanivorax were between 76.8 and 80.8 %. The principal fatty acids were C(12 : 0) 3-OH (8.0 %), C(16 : 0) (29.1 %) and C(18 : 1)ω7c (27.4 %). The G+C content of the chromosomal DNA was 60.8 mol%. Based on its morphology, physiology and fatty acid composition as well as the results of 16S rRNA and gyrB gene sequence analyses, strain W11-5(T) (â=âMCCC 1A00474(T) â= CCTCC AB 208236(T) â=âLMG 25514(T)) represents a novel species of the genus Alcanivorax, for which the name Alcanivorax pacificus sp. nov. is proposed.
Assuntos
Alcanivoraceae/isolamento & purificação , Alcanivoraceae/metabolismo , Sedimentos Geológicos/microbiologia , Pirenos/metabolismo , Alcanivoraceae/genética , Alcanivoraceae/fisiologia , Composição de Bases , Catalase/metabolismo , Análise por Conglomerados , DNA Girase/genética , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Ácidos Graxos/análise , Dados de Sequência Molecular , Oxirredutases/metabolismo , Oceano Pacífico , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Cloreto de Sódio/metabolismo , TemperaturaRESUMO
A taxonomic study was carried out on strain F44-8(T), which was isolated from a crude-oil-degrading consortium, enriched from marine sediment of the Beibu Gulf, PR China. The 16S rRNA gene sequence of strain F44-8(T) showed highest similarities to those of Flavobacterium frigoris LMG 21922(T) (93.3â%), Flavobacterium terrae R2A1-13(T) (93.3â%) and Flavobacterium gelidilacus LMG 21477(T) (93.1â%). Sequence similarities to other members of the genus Flavobacterium were <93.0â%. The dominant fatty acids of strain F44-8(T) were iso-C(15â:â0), summed feature 3 (iso-C(15â:â0) 2-OH and/or C(16â:â1)ω7c), iso-C(15â:â1) G and iso-C(17â:â0) 3-OH. The DNA G+C content of strain F44-8(T) was 38.6 mol%. These results are consistent with characteristics of members of the genus Flavobacterium. Strain F44-8(T) could, however, be readily distinguished from all known Flavobacterium species by a number of phenotypic features. Therefore, according to the phenotypic and 16S rRNA gene sequence data, strain F44-8(T) represents a novel species in the genus Flavobacterium, for which the name Flavobacterium beibuense sp. nov. is proposed (type strain F44-8(T) =CCTCC AB 209067(T) =LMG 25233(T) =MCCC 1A02877(T)).
Assuntos
Flavobacterium/classificação , Flavobacterium/isolamento & purificação , Sedimentos Geológicos/microbiologia , Composição de Bases , China , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Ácidos Graxos/análise , Flavobacterium/genética , Dados de Sequência Molecular , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
Strain pht-3B(T) was isolated from a pyrene-degrading consortium of an enriched sediment from the Pacific Ocean, collected during the screening of polycyclic aromatic hydrocarbon-degrading bacteria. Cells were Gram-negative, short rods that were motile by means of flagella. Growth was observed at 0-7 % NaCl and 10-41 °C. The isolate was able to reduce nitrate to nitrite, but not to nitrogen. 16S rRNA gene sequence comparisons showed that strain pht-3B(T) was most closely related to Nitratireductor aquibiodomus NL21(T) (97.3 % 16S rRNA gene sequence similarity), N. indicus C115(T) (97.1 %), N. basaltis J3(T) (96.8 %) and N. kimnyeongensis KY 101(T) (96.7 %). DNA-DNA hybridization between strain pht-3B(T) and these reference strains revealed 55, 54, 28 and 42 % DNA-DNA relatedness, respectively. The dominant fatty acids were C(19 : 0)ω8c cyclo (22.6 %) and summed feature 8 (consisting of C(18 : 1)ω7c and/or C(18 : 1)ω6c; 60.4 %). The G+C content of the chromosomal DNA was 63 mol%. These characteristics were in good agreement with those of members of the genus Nitratireductor. According to cell morphology, physiology, fatty acid composition, 16S rRNA gene sequence analysis and DNA-DNA relatedness, the isolate belonged to the genus Nitratireductor but could be readily distinguished from recognized species of the genus. Therefore a novel species is proposed to accommodate strain pht-3B(T), for which the name Nitratireductor pacificus sp. nov. is proposed. The type strain is pht-3B(T) (â=âCCTCC AB 209302(T)â=âLMG 25541(T)â=âMCCC 1A01024(T)).
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Alphaproteobacteria/classificação , Alphaproteobacteria/isolamento & purificação , Sedimentos Geológicos/microbiologia , Pirenos/metabolismo , Alphaproteobacteria/genética , Alphaproteobacteria/fisiologia , Composição de Bases , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Ácidos Graxos/análise , Flagelos/fisiologia , Locomoção , Dados de Sequência Molecular , Nitratos/metabolismo , Nitritos/metabolismo , Hibridização de Ácido Nucleico , Oxirredução , Oceano Pacífico , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Cloreto de Sódio/metabolismo , TemperaturaRESUMO
High-quality and comprehensive reference gene catalogs are essential for metagenomic research. The rather low diversity of samples used to construct existing catalogs of the mouse gut metagenome limits the numbers of identified genes in existing catalogs. We therefore established an expanded catalog of genes in the mouse gut metagenome (EMGC) containing >5.8 million genes by integrating 88 newly sequenced samples, 86 mouse gut-related bacterial genomes, and 3 existing gene catalogs. EMGC increases the number of nonredundant genes by more than 1 million genes compared to the so-far most extensive catalog. More than 60% of the genes in EMGC were assigned to Bacteria, with 54.20% being assigned to a phylum and 35.33% to a genus, while 30.39% were annotated at the KEGG orthology level. Nine hundred two metagenomic species (MGS) assigned to 122 taxa are identified based on the EMGC. The EMGC-based analysis of samples from groups of mice originating from different animal providers, housing laboratories, and genetic strains substantiated that diet is a major contributor to differences in composition and functional potential of the gut microbiota irrespective of differences in environment and genetic background. We envisage that EMGC will serve as a valuable reference data set for future metagenomic studies in mice.IMPORTANCE We established an expanded gene catalog of the mouse gut metagenome not only to increase the sample size compared to that in existing catalogs but also to provide a more comprehensive reference data set of the mouse gut microbiome for bioinformatic analysis. The expanded gene catalog comprises more than 5.8 million unique genes, as well as a wide range of taxonomic and functional information. Particularly, the analysis of metagenomic species with the expanded gene catalog reveals a great novelty of mouse gut-inhabiting microbial species. We envisage that the expanded gene catalog of the mouse gut metagenome will serve as a valuable bioinformatic resource for future gut metagenomic studies in mice.
Assuntos
Bactérias/genética , Microbioma Gastrointestinal/genética , Genoma Bacteriano , Metagenoma , Animais , Bactérias/classificação , Bactérias/isolamento & purificação , Biologia Computacional/métodos , Fezes/microbiologia , Masculino , Metagenômica , Camundongos , Camundongos Endogâmicos C57BL , FilogeniaRESUMO
INTRODUCTION: Clostridioides (Clostridium) difficile infection, the leading cause of healthcare-associated diarrhea, represents a significant burden on global healthcare systems. Despite being a global issue, information on C. difficile from a global perspective is lacking. The aim of this study is to model the global phylogeography of clinical C. difficile. METHODS: Using samples collected from the MODIFY I and II studies (NCT01241552, NCT01513239), we performed whole-genome sequencing of 1501 clinical isolates including 37 novel sequence types (STs), representing the largest worldwide collection to date. RESULTS: Our data showed ribotypes, multi-locus sequence typing clades, and whole-genome phylogeny were in good accordance. The clinical C. difficile genome was found to be more conserved than previously reported (61% core genes), and modest recombination rates of 1.4-5.0 were observed across clades. We observed a significant continent distribution preference among five C. difficile clades (Benjamini-Hochberg corrected Fisher's exact test P < 0.01); moreover, weak association between geographic and genetic distance among ribotypes suggested sources beyond healthcare-related transmission. Markedly different trends of antibiotic susceptibility among lineages and regions were identified, and three novel mutations (in pyridoxamine 5'-phosphate oxidase family protein: Tyr130Ser, Tyr130Cys, and a promoter SNP) associated with metronidazole-reduced susceptibility were discovered on a nim-related gene and its promotor by genome-wide association study. Toxin gene polymorphisms were shown to vary within and between prevalent ribotypes, and novel severe mutations were found on the tcdC toxin regulator protein. CONCLUSION: Our systematic characterization of a global set of clinical trial C. difficile isolates from infected individuals demonstrated the complexity of the genetic makeup of this pathogenic organism. The geographic variability of clades, variability in toxin genes, and mutations associated with antibiotic susceptibility indicate a highly complex interaction of C. difficile between host and environment. This dataset will provide a useful resource for validation of findings and future research of C. difficile.
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The gut microbiome has been established as a key environmental factor to health. Genetic influences on the gut microbiome have been reported, yet, doubts remain as to the significance of genetic associations. Here, we provide shotgun data for whole genome and whole metagenome from a Chinese cohort, identifying no <20% genetic contribution to the gut microbiota. Using common variants-, rare variants-, and copy number variations-based association analyses, we identified abundant signals associated with the gut microbiome especially in metabolic, neurological, and immunological functions. The controversial concept of enterotypes may have a genetic attribute, with the top two loci explaining 11% of the Prevotella-Bacteroides variances. Stratification according to gender led to the identification of differential associations in males and females. Our two-stage metagenome genome-wide association studies on a total of 1295 individuals unequivocally illustrates that neither microbiome nor GWAS studies could overlook one another in our quest for a better understanding of human health and diseases.
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Lifelong sex- and age-related trajectories of the human gut microbiota remain largely unexplored. Using metagenomics, we derived the gut microbial composition of 2,338 adults (26-76 years) from a Han Chinese population-based cohort where metabolic health, hormone levels and aspects of their lifestyles were also recorded. In this cohort, and in three independent cohorts distributed across China, Israel and the Netherlands, we observed sex differences in the gut microbial composition and a shared age-related decrease in sex-dependent differences in gut microbiota. Compared to men, the gut microbiota of premenopausal women exhibited higher microbial diversity and higher abundances of multiple species known to have beneficial effects on host metabolism. We also found consistent sex-independent, age-related gut microbial characteristics across all populations, with the presence of members of the oral microbiota being the strongest indicator of older chronological age. Our findings highlight the existence of sex- and age-related trajectories in the human gut microbiota that are shared between populations of different ethnicities and emphasize the pivotal links between sex hormones, gut microbiota and host metabolism.
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Microbioma Gastrointestinal , Microbiota , Humanos , Feminino , Adulto , Masculino , Microbioma Gastrointestinal/genética , Fezes , Etnicidade , MetagenômicaRESUMO
Comprehensive analyses of multi-omics data may provide insights into interactions between different biological layers concerning distinct clinical features. We integrated data on the gut microbiota, blood parameters and urine metabolites of treatment-naive individuals presenting a wide range of metabolic disease phenotypes to delineate clinically meaningful associations. Trans-omics correlation networks revealed that candidate gut microbial biomarkers and urine metabolite feature were covaried with distinct clinical phenotypes. Integration of the gut microbiome, the urine metabolome and the phenome revealed that variations in one of these three systems correlated with changes in the other two. In a specific note about clinical parameters of liver function, we identified Eubacteriumeligens, Faecalibacteriumprausnitzii and Ruminococcuslactaris to be associated with a healthy liver function, whereas Clostridium bolteae, Tyzzerellanexills, Ruminococcusgnavus, Blautiahansenii, and Atopobiumparvulum were associated with blood biomarkers for liver diseases. Variations in these microbiota features paralleled changes in specific urine metabolites. Network modeling yielded two core clusters including one large gut microbe-urine metabolite close-knit cluster and one triangular cluster composed of a gut microbe-blood-urine network, demonstrating close inter-system crosstalk especially between the gut microbiome and the urine metabolome. Distinct clinical phenotypes are manifested in both the gut microbiome and the urine metabolome, and inter-domain connectivity takes the form of high-dimensional networks. Such networks may further our understanding of complex biological systems, and may provide a basis for identifying biomarkers for diseases. Deciphering the complexity of human physiology and disease requires a holistic and trans-omics approach integrating multi-layer data sets, including the gut microbiome and profiles of biological fluids. By studying the gut microbiome on carotid atherosclerosis, we identified microbial features associated with clinical parameters, and we observed that groups of urine metabolites correlated with groups of clinical parameters. Combining the three data sets, we revealed correlations of entities across the three systems, suggesting that physiological changes are reflected in each of the omics. Our findings provided insights into the interactive network between the gut microbiome, blood clinical parameters and the urine metabolome concerning physiological variations, and showed the promise of trans-omics study for biomarker discovery.