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1.
PLoS Genet ; 15(3): e1008018, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30849075

RESUMO

Several bacteria in the gut microbiota have been shown to be associated with inflammatory bowel disease (IBD), and dozens of IBD genetic variants have been identified in genome-wide association studies. However, the role of the microbiota in the etiology of IBD in terms of host genetic susceptibility remains unclear. Here, we studied the association between four major genetic variants associated with an increased risk of IBD and bacterial taxa in up to 633 IBD cases. We performed systematic screening for associations, identifying and replicating associations between NOD2 variants and two taxa: the Roseburia genus and the Faecalibacterium prausnitzii species. By exploring the overall association patterns between genes and bacteria, we found that IBD risk alleles were significantly enriched for associations concordant with bacteria-IBD associations. To understand the significance of this pattern in terms of the study design and known effects from the literature, we used counterfactual principles to assess the fitness of a few parsimonious gene-bacteria-IBD causal models. Our analyses showed evidence that the disease risk of these genetic variants were likely to be partially mediated by the microbiome. We confirmed these results in extensive simulation studies and sensitivity analyses using the association between NOD2 and F. prausnitzii as a case study.


Assuntos
Microbioma Gastrointestinal/genética , Interações entre Hospedeiro e Microrganismos/genética , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/microbiologia , Adulto , Proteínas Adaptadoras de Sinalização CARD/genética , Clostridiales/genética , Clostridiales/isolamento & purificação , Clostridiales/patogenicidade , Faecalibacterium prausnitzii/genética , Faecalibacterium prausnitzii/isolamento & purificação , Faecalibacterium prausnitzii/patogenicidade , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Variação Genética , Humanos , Doenças Inflamatórias Intestinais/etiologia , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Proteína Adaptadora de Sinalização NOD2/genética , Polimorfismo de Nucleotídeo Único
2.
J Gastroenterol Hepatol ; 36(2): 320-328, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32815163

RESUMO

BACKGROUND AND AIM: We comprehensively carry out a systematic review and meta-analysis of previous studies to determine the association between intestinal Faecalibacterium prausnitzii (F. prausnitzii) and inflammatory bowel disease (IBD) in human studies. METHODS: A systematic literature search of PubMed, Embase, and the Cochrane Library database was conducted until April 1, 2020. Inclusion criteria were studies involving patients with Crohn's disease (CD) or ulcerative colitis (UC) with abundance of F. prausnitzii. The quality of the studies was assessed by the modified Newcastle-Ottawa scale. RESULTS: A total of 1669 subjects (427 CD patients, 560 UC patients, and 682 healthy controls) were enrolled from 16 studies. Both CD (standardized mean difference [SMD]: -1.36; 95% CI, -1.74 to -0.98; P < 0.00001) and UC patients (SMD: -0.81; 95% CI, -1.21 to -0.42; P < 0.0001) had a lower abundance of F. prausnitzii than the healthy controls. Compared with the IBD remission patients, the IBD active patients had lower levels of F. prausnitzii (SMD: -0.56; 95% CI, -0.91 to -0.21; P = 0.002). In the subgroup analyses, the abundance of F. prausnitzii was reduced in both active CD patients (SMD: -0.78; 95% CI, -1.51 to -0.04; P = 0.04) and active UC patients (SMD:-0.44; 95%CI, -0.81 to -0.07; P = 0.02) when compared with the patients with CD or UC in remission, respectively. CONCLUSION: A negative association between abundance of F. prausnitzii and IBD activity is observed, but a cut-off level of F. prausnitzii to diagnose and/or to start treating IBD is not determined.


Assuntos
Colite Ulcerativa/microbiologia , Doença de Crohn/microbiologia , Faecalibacterium prausnitzii/isolamento & purificação , Mucosa Intestinal/microbiologia , Faecalibacterium prausnitzii/fisiologia , Humanos
3.
Scand J Gastroenterol ; 54(5): 577-585, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31104514

RESUMO

Objectives: Crohn's disease is characterized by a gut dysbiosis with decreased abundance of butyrate producers such as Faecalibacterium prausnitzii. Although F. prausnitzii secretes anti-inflammatory molecules, few studies have addressed the importance of F. prausnitzii in a longitudinal setting. We aimed to examine the relationship between temporal profiles of F. prausnitzii, the C. leptum group, overall butyrate production, and inflammatory activity. Material and methods: Fecal samples (n = 59) were collected every third month from nine patients with ileal Crohn's disease. The abundance of F. prausnitzii and C. leptum was quantified relative to the total amount of bacteria using quantitative-PCR. To assess butyrate production of gut microbiota, gene copy numbers of the butyryl-CoA:acetate-CoA transferase (BCoAT) gene were quantified by qPCR. The inflammatory activity was defined by fecal (f)-calprotectin. Results: No correlation between the relative abundance of F. prausnitzii, the C. leptum group, or copy numbers of the BCoAT gene, and f-calprotectin was observed in the total sample set. By analyzing alterations between consecutive samples, a negative correlation between changes in the relative abundance of F. prausnitzii and f-calprotectin was observed (R = -0.39; p = .009). Changes in C. leptum (R = -0.18, p = .23) and number of copies of the BCoAT gene (R = -0.12; p = .42) did not correlate with f-calprotectin. Conclusions: There was an inverse correlation between temporal changes in the relative abundance of F. prausnitzii, but not overall butyrate producing capacity, and changes in inflammatory activity in ileal Crohn's disease. These findings indicate that F. prausnitzii may play a role in gut homeostasis, even though causality is still to be demonstrated.


Assuntos
Doença de Crohn/microbiologia , Faecalibacterium prausnitzii/isolamento & purificação , Íleo/microbiologia , Complexo Antígeno L1 Leucocitário/análise , Adolescente , Adulto , Estudos de Casos e Controles , Doença de Crohn/metabolismo , Disbiose/etiologia , Fezes/química , Fezes/microbiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , RNA Ribossômico 16S/análise , Reação em Cadeia da Polimerase em Tempo Real , Suécia , Adulto Jovem
4.
Appl Microbiol Biotechnol ; 102(3): 1455-1466, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29250719

RESUMO

The poultry industry aims to improve productivity while maintaining the health and welfare of flocks. Pathogen control has been achieved through biosecurity, vaccinations and the use of antibiotics. However, the emergence of antibiotic resistance, in animal and human pathogens, has prompted researchers and chicken growers alike to seek alternative approaches. The use of new and emerging approaches to combat pathogen activity including nanotechnology, in particular, silver nanoparticles (NPs), has been found to not only eradicate pathogenic bacteria but also include issues of toxicity and bioaccumulation effects. Other novel metal nanoparticles could provide this pathogen reducing property with a more tailored and biocompatible nanomaterial for the model used, something our study represents. This study investigated the benefits of nanomaterial delivery mechanisms coupled with important health constituents using selenium as a biocompatible metal to minimise toxicity properties. Selenium NPs were compared to two common forms of bulk selenium macronutrients already used in the poultry industry. An intermediate concentration of selenium nanoparticles (0.9 mg/kg) demonstrated the best performance, improving the gut health by increasing the abundance of beneficial bacteria, such as Lactobacillus and Faecalibacterium, and short-chain fatty acids (SCFAs), in particular butyric acid. SCFAs are metabolites produced by the intestinal tract and are used as an energy source for colonic cells and other important bodily functions. Selenium nanoparticles had no significant effect on live weight gain or abundance of potentially pathogenic bacteria.


Assuntos
Ração Animal , Faecalibacterium prausnitzii/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Nanopartículas Metálicas/administração & dosagem , Selênio/administração & dosagem , Animais , Butiratos/metabolismo , Galinhas , Faecalibacterium prausnitzii/isolamento & purificação , Ácidos Graxos Voláteis/biossíntese , Fezes/microbiologia , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/microbiologia , Lactobacillus/efeitos dos fármacos , Nanopartículas Metálicas/química , Aves Domésticas , Selênio/química
5.
Microb Pathog ; 110: 630-636, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28739439

RESUMO

It is known that type 2 diabetes (T2D) in humans could be linked to the composition of gut microbiota. The aim of this study was to evaluate three faecal bacterial species, including Bacteroides fragilis, Bifidobacterium longum and Faecalibacterium prausnitzii in patients with T2D. This case control study included 18 patients with T2D and 18 matched persons without diabetes. The concentrations of B. fragilis, B. longum and F. prausnitzii were determined by quantitative Real-Time PCR. Quantitative PCR analysis revealed that the gut bacterial composition in patients with T2D was partially different from that in the healthy individuals. Faecalibacterium prausnitzii was significantly lower in patients with T2D (P-value = 0.038). Bacteroides fragilis was under-represented in the microbiota of the group with diabetes, but its difference between two groups was not significant (P-value = 0.38). No difference was observed for B. longum community between the both groups (P-value = 0.99). Characterization of specific species of intestinal microbiota shows some compositional changes in patients with T2D. The results may be valuable for developing strategies to control type 2 diabetes by modifying the intestinal microbiota. Long-term studies with emphasis on other bacterial groups are suggested to clarify the association of T2D with gut microbiota.


Assuntos
Bacteroides fragilis/isolamento & purificação , Bifidobacterium longum/isolamento & purificação , Diabetes Mellitus Tipo 2/microbiologia , Faecalibacterium prausnitzii/isolamento & purificação , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Carga Bacteriana , Estudos de Casos e Controles , Fezes/microbiologia , Humanos , Irã (Geográfico) , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real
6.
Gut ; 65(6): 944-53, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-25856344

RESUMO

OBJECTIVE: To determine the existence of mucosal dysbiosis in siblings of patients with Crohn's disease (CD) using 454 pyrosequencing and to comprehensively characterise and determine the influence of genotypical and phenotypical factors, on that dysbiosis. Siblings of patients with CD have elevated risk of developing CD and display aspects of disease phenotype, including faecal dysbiosis. Whether the mucosal microbiota is disrupted in these at-risk individuals is unknown. DESIGN: Rectal biopsy DNA was extracted from 21 patients with quiescent CD, 17 of their healthy siblings and 19 unrelated healthy controls. Mucosal microbiota was analysed by 16S rRNA gene pyrosequencing and were classified into core and rare species. Genotypical risk was determined using Illumina Immuno BeadChip, faecal calprotectin by ELISA and blood T-cell phenotype by flow cytometry. RESULTS: Core microbiota of both patients with CD and healthy siblings was significantly less diverse than controls. Metacommunity profiling (Bray-Curtis (SBC) index) showed the sibling core microbial composition to be more similar to CD (SBC=0.70) than to healthy controls, whereas the sibling rare microbiota was more similar to healthy controls (SBC=0.42). Faecalibacterium prausnitzii contributed most to core metacommunity dissimilarity both between siblings and controls, and between patients and controls. Phenotype/genotype markers of CD risk significantly influenced microbiota variation between and within groups, of which genotype had the largest effect. CONCLUSIONS: Individuals with elevated CD-risk display mucosal dysbiosis characterised by reduced diversity of core microbiota and lower abundance of F. prausnitzii. This dysbiosis in healthy people at risk of CD implicates microbiological processes in CD pathogenesis.


Assuntos
Doença de Crohn/microbiologia , Doença de Crohn/patologia , Disbiose/microbiologia , Microbiota , Irmãos , Adolescente , Adulto , Biópsia , Estudos de Casos e Controles , Doença de Crohn/genética , Faecalibacterium prausnitzii/isolamento & purificação , Fezes/microbiologia , Feminino , Genótipo , Humanos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Intestinos/microbiologia , Masculino , Fenótipo
7.
Pediatr Res ; 80(6): 844-851, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27537603

RESUMO

BACKGROUND: Although Faecalibacterium prausnitzii is a major bacterium in the intestine of adults, which is known to have anti-inflammatory effects, the development in infants or the response to prebiotics remains unclear. METHODS: The counts of F. prausnitzii in the feces were examined by real-time polymerase chain reaction (PCR). Fecal samples were obtained from 65 atopic dermatitis (AD) infants who participated in a randomized controlled clinical trial to investigate the therapeutic effect of kestose, the smallest fructooligosaccharide. RESULTS: Although the F. prausnitzii count was undetectable level in most 0- to 1-y-old infants, the count reached a level comparable to that in adults in 2- to 5-y-old infants. The bacterial number increased about 10-fold by oral administration of kestose every day for 12 wk in the younger infants, but not so much in the older infants. This bacterial increase was significantly correlated with an improvement in the AD symptoms in the older infants. CONCLUSION: The F. prausnitzii population in the intestine reaches a level comparable to that in adult at approximately 2 y of age. Kestose efficiently stimulates the growth of this bacterium in the intestine, which might lead to an improvement in AD symptoms in infants.


Assuntos
Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/microbiologia , Faecalibacterium prausnitzii/efeitos dos fármacos , Oligossacarídeos/uso terapêutico , Prebióticos/administração & dosagem , Fatores Etários , Carga Bacteriana , Bifidobacterium/efeitos dos fármacos , Bifidobacterium/genética , Bifidobacterium/isolamento & purificação , Pré-Escolar , Faecalibacterium prausnitzii/genética , Faecalibacterium prausnitzii/isolamento & purificação , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Masculino , Reação em Cadeia da Polimerase em Tempo Real
8.
PLoS One ; 16(4): e0249861, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33836037

RESUMO

OBJECTIVE: Fecal microbiota transplantation (FMT) is a highly effective treatment for Clostridioides difficile infection (CDI). However, the fecal transplant's causal components translating into clearance of the CDI are yet to be identified. The commensal bacteria Faecalibacterium prausnitzii may be of great interest in this context, since it is one of the most common species of the healthy gut microbiota and produces metabolites with anti-inflammatory properties. Although there is mounting evidence that F. prausnitzii is an important regulator of intestinal homeostasis, data about its role in CDI and FMT are relatively scarce. METHODS: Stool samples from patients with recurrent CDI were collected to investigate the relative abundance of F. prausnitzii before and after FMT. Twenty-one patients provided fecal samples before the FMT procedure, at 2 weeks post-FMT, and at 2-4 months post-FMT. The relative abundance of F. prausnitzii was determined using quantitative polymerase chain reaction. RESULTS: The abundance of F. prausnitzii was elevated in samples (N = 9) from donors compared to pre-FMT samples (N = 15) from patients (adjusted P<0.001). No significant difference in the abundance of F. prausnitzii between responders (N = 11) and non-responders (N = 4) was found before FMT (P = 0.85). In patients with CDI, the abundance of F. prausnitzii significantly increased in the 2 weeks post-FMT samples (N = 14) compared to the pre-FMT samples (N = 15, adjusted P<0.001). The increase persisted 2-4 months post-FMT (N = 15) compared to pre-FMT samples (N = 15) (adjusted P<0.001). CONCLUSIONS: FMT increases the relative abundance of F. prausnitzii in patients with recurrent CDI, and this microbial shift remains several months later. The baseline abundance of F. prausnitzii in donors or recipients was not associated with future treatment response, although a true predictive capacity cannot be excluded because of the limited sample size. Further studies are needed to discern whether F. prausnitzii plays an active role in the resolution of CDI.


Assuntos
Infecções por Clostridium/terapia , Faecalibacterium prausnitzii/isolamento & purificação , Transplante de Microbiota Fecal , Fezes/microbiologia , Idoso , Bactérias/genética , Bactérias/isolamento & purificação , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Feminino , Microbioma Gastrointestinal , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva
9.
Cell Rep Med ; 2(9): 100398, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34622235

RESUMO

Evidence linking the gut-brain axis to Alzheimer's disease (AD) is accumulating, but the characteristics of causally important microbes are poorly understood. We perform a fecal microbiome analysis in healthy subjects and those with mild cognitive impairment (MCI) and AD. We find that Faecalibacterium prausnitzii (F. prausnitzii) correlates with cognitive scores and decreases in the MCI group compared with the healthy group. Two isolated strains from the healthy group, live Fp360 and pasteurized Fp14, improve cognitive impairment in an AD mouse model. Whole-genome comparison of isolated strains reveals specific orthologs that are found only in the effective strains and are more abundant in the healthy group compared with the MCI group. Metabolome and RNA sequencing analyses of mouse brains provides mechanistic insights into the relationship between the efficacy of pasteurized Fp14, oxidative stress, and mitochondrial function. We conclude that F. prausnitzii strains with these specific orthologs are candidates for gut microbiome-based intervention in Alzheimer's-type dementia.


Assuntos
Doença de Alzheimer/microbiologia , Demência/microbiologia , Faecalibacterium prausnitzii/fisiologia , Microbioma Gastrointestinal , Idoso , Peptídeos beta-Amiloides/metabolismo , Encéfalo/microbiologia , Encéfalo/patologia , Cognição , Disfunção Cognitiva/microbiologia , Faecalibacterium prausnitzii/genética , Faecalibacterium prausnitzii/isolamento & purificação , Feminino , Genoma Bacteriano , Humanos , Masculino , Metaboloma/genética , Metagenoma , Pasteurização , Análise de Componente Principal , RNA-Seq
10.
Nat Commun ; 12(1): 5958, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645820

RESUMO

Understanding the functional potential of the gut microbiome is of primary importance for the design of innovative strategies for allergy treatment and prevention. Here we report the gut microbiome features of 90 children affected by food (FA) or respiratory (RA) allergies and 30 age-matched, healthy controls (CT). We identify specific microbial signatures in the gut microbiome of allergic children, such as higher abundance of Ruminococcus gnavus and Faecalibacterium prausnitzii, and a depletion of Bifidobacterium longum, Bacteroides dorei, B. vulgatus and fiber-degrading taxa. The metagenome of allergic children shows a pro-inflammatory potential, with an enrichment of genes involved in the production of bacterial lipo-polysaccharides and urease. We demonstrate that specific gut microbiome signatures at baseline can be predictable of immune tolerance acquisition. Finally, a strain-level selection occurring in the gut microbiome of allergic subjects is identified. R. gnavus strains enriched in FA and RA showed lower ability to degrade fiber, and genes involved in the production of a pro-inflammatory polysaccharide. We demonstrate that a gut microbiome dysbiosis occurs in allergic children, with R. gnavus emerging as a main player in pediatric allergy. These findings may open new strategies in the development of innovative preventive and therapeutic approaches. Trial: NCT04750980.


Assuntos
Alérgenos/imunologia , Hipersensibilidade Alimentar/microbiologia , Microbioma Gastrointestinal/imunologia , Tolerância Imunológica , Hipersensibilidade Respiratória/microbiologia , Alérgenos/efeitos adversos , Animais , Bacteroides/isolamento & purificação , Bacteroides/metabolismo , Bifidobacterium longum/isolamento & purificação , Bifidobacterium longum/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Clostridiales/isolamento & purificação , Clostridiales/metabolismo , Alérgenos Animais/efeitos adversos , Alérgenos Animais/imunologia , Ovos/efeitos adversos , Faecalibacterium prausnitzii/isolamento & purificação , Faecalibacterium prausnitzii/metabolismo , Feminino , Hipersensibilidade Alimentar/etiologia , Hipersensibilidade Alimentar/imunologia , Humanos , Lipopolissacarídeos/biossíntese , Masculino , Leite/efeitos adversos , Leite/imunologia , Nozes/efeitos adversos , Nozes/imunologia , Pólen/química , Pólen/imunologia , Prunus persica/química , Prunus persica/imunologia , Pyroglyphidae/química , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/etiologia , Hipersensibilidade Respiratória/imunologia , Urease/biossíntese
11.
Indian J Gastroenterol ; 39(2): 133-140, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32388710

RESUMO

Colonization of the gut by microbes depends on a number of factors including age, diet, genetic makeup, gender, geographic location, and health status of an individual. India is a megadiverse country and includes 4 biodiversity hot spots. These features, along with the transitioning Indian sociodemographic profile, make the gut microbiota of Indian subjects an interesting area to study. In this review, we critically discuss the present status of the gut microbiome in the Indian population and its difference from other populations. We also discuss the aberrations in the available study designs that could introduce heterogeneity. An ideal study to evaluate the core gut microbiota of healthy Indians should involve a large homogeneous population across the country and use the same technology and data analytics tools. The "Landscape of Gut Microbiome-Pan India Exploration" (LogMPIE) is such a study that confirmed the most predominant organisms in Indians to be Prevotella copri and Faecalibacterium prausnitzii.


Assuntos
Microbioma Gastrointestinal , Voluntários Saudáveis , Intestinos/microbiologia , Adulto , Fatores Etários , Dieta , Faecalibacterium prausnitzii/isolamento & purificação , Feminino , Genética Populacional , Humanos , Índia/etnologia , Masculino , Prevotella/isolamento & purificação
12.
PLoS One ; 15(1): e0227373, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31910227

RESUMO

METHODS: Patients transplanted at our institution provided fecal samples before, and 3-9 months after KT. Fecal bacterial DNA was extracted and 9 bacteria or bacterial groups were quantified by qPCR. RESULTS: 50 patients (19 controls without diabetes, 15 who developed New Onset Diabetes After Transplantation, NODAT, and 16 with type 2 diabetes before KT) were included. Before KT, Lactobacillus sp. tended to be less frequently detected in controls than in those who would become diabetic following KT (NODAT) and in initially diabetic patients (60%, 87.5%, and 100%, respectively, p = 0.08). The relative abundance of Faecalibacterium prausnitzii was 30 times lower in initially diabetic patients than in controls (p = 0.002). The relative abundance of F. prausnitzii of NODAT patients was statistically indistinguishable from controls and from diabetic patients. The relative abundance of Lactobacillus sp. increased following KT in NODAT and in initially diabetic patients (20-fold, p = 0.06, and 25-fold, p = 0.02, respectively). In contrast, the proportion of Akkermansia muciniphila decreased following KT in NODAT and in initially diabetic patients (2,500-fold, p = 0.04, and 50,000-fold, p<0.0001, respectively). The proportion of Lactobacillus and A. muciniphila did not change in controls between before and after the transplantation. Consequently, after KT the relative abundance of Lactobacillus sp. was 25 times higher (p = 0.07) and the relative abundance of A. muciniphila was 2,000 times lower (p = 0.002) in diabetics than in controls. CONCLUSION: An alteration of the gut microbiota composition involving Lactobacillus sp., A. muciniphila and F. prausnitzii is associated with the glycemic status in KT recipients, raising the question of their role in the genesis of NODAT.


Assuntos
DNA Bacteriano/genética , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal/genética , Transplante de Rim/efeitos adversos , Akkermansia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Faecalibacterium prausnitzii/genética , Faecalibacterium prausnitzii/isolamento & purificação , Faecalibacterium prausnitzii/metabolismo , Fezes/microbiologia , Feminino , Humanos , Lactobacillus/genética , Lactobacillus/isolamento & purificação , Lactobacillus/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Verrucomicrobia/genética , Verrucomicrobia/isolamento & purificação , Verrucomicrobia/metabolismo
13.
United European Gastroenterol J ; 8(3): 293-302, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32213018

RESUMO

OBJECTIVES: Many countries use faecal immunochemical testing (FIT) to screen for colorectal cancer. There is increasing evidence that faecal microbiota play a crucial role in colorectal cancer carcinogenesis. We assessed the possibility of measuring faecal microbial features in FIT as potential future biomarkers in colorectal cancer screening. METHODS: Bacterial stability over time and the possibility of bacterial contamination were evaluated using quantitative polymerase chain reaction analysis. Positive FIT samples (n = 200) of an average-risk screening cohort were subsequently analysed for universal 16S, and bacteria. Escherichia coli (E. coli), Fusobacterium nucleatum (F. nucleatum), Bacteroidetes and Faecalibacterium prausnitzii (F. prausnitzii) by qPCR. The results were compared with colonoscopy findings. RESULTS: Faecal microbiota in FIT were stably measured up to six days for E. coli (p = 0.53), F. nucleatum (p = 0.30), Bacteroidetes (p = 0.05) and F. prausnitzii (p = 0.62). Overall presence of bacterial contamination in FIT controls was low. Total bacterial load (i.e. 16S) was significantly higher in patients with colorectal cancer and high-grade dysplasia (p = 0.006). For the individual bacteria tested, no association was found with colonic lesions. CONCLUSIONS: These results show that the faecal microbial content can be measured in FIT samples and remains stable for six days. Total bacterial load was higher in colorectal cancer and high-grade dysplasia. These results pave the way for further research to determine the potential role of microbiota assessment in FIT screening.


Assuntos
Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Fezes/microbiologia , Microbioma Gastrointestinal , Programas de Rastreamento/métodos , Idoso , Carga Bacteriana , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , Colo/diagnóstico por imagem , Colo/microbiologia , Colo/patologia , Colonoscopia , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/patologia , DNA Bacteriano/isolamento & purificação , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Faecalibacterium prausnitzii/genética , Faecalibacterium prausnitzii/isolamento & purificação , Estudos de Viabilidade , Fezes/química , Feminino , Fusobacterium nucleatum/genética , Fusobacterium nucleatum/isolamento & purificação , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Países Baixos , Sangue Oculto , RNA Ribossômico 16S/genética , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA
14.
Sci Rep ; 9(1): 8327, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171823

RESUMO

Stool collection devices minimizing the exposure of gut bacteria to oxygen are critical for the standardization of further microbiota-based studies, analysis and developments. The aim of this work was to evidence that keeping anaerobiosis has a deep impact on the viability and diversity of the fecal microbiota that is recovered in the laboratory. Recovering certain microbial populations, such as obligate anaerobic bacteria, is particularly critical if the purpose of the study is to envisage personalized therapeutic purposes, such as autologous Fecal Microbiota Transplant. In this study the same fecal specimens were sampled in conventional stool containers and GutAlive, a disposable device that minimizes exposure of the gut microbiota to oxygen. Samples from five healthy donors were analysed and 150 differential colonies were recovered and identified by 16S rRNA gene sequencing. Globally, GutAlive maintained extremely oxygen sensitive (EOS) populations that were lost in conventional stool containers, and thus viability of species such as as Akkermansia muciniphila, Faecalibacterium prausnitzii and a novel member of the Clostridiales order was kept. These obligate anaerobes were not recovered using the conventional stool collection device. In conclusion, the use of GutAlive for stool collection and transport optimized the viability and recovery of EOS bacteria in the lab by diminishing oxygen toxicity.


Assuntos
Bactérias/isolamento & purificação , Fezes/microbiologia , Microbioma Gastrointestinal , Manejo de Espécimes/métodos , Adulto , Akkermansia , Anaerobiose , Clostridiales/isolamento & purificação , Faecalibacterium prausnitzii/isolamento & purificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/metabolismo , RNA Ribossômico 16S/genética , Verrucomicrobia/isolamento & purificação
15.
PLoS One ; 14(2): e0211973, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30730969

RESUMO

BACKGROUND: Intestinal permeability can be assessed by monitoring renal excretion of orally administered radioactively 51Cr-labeled ethylenediaminetetraacetic acid (51Cr-EDTA). Although considered safe, patient participation in using radio-labeled tracers is low. Here, we used orally administered 52Cr-EDTA as non-radioactive alternative to assess intestinal permeability in CD and analyzed the association with disease activity, disease location and gut microbial dysbiosis. MATERIALS AND METHODS: 60 CD patients with low (n = 25) and increased (n = 35) fecal calprotectin levels (cut-off: 100 µg/g feces) ingested 20 mL 52Cr-EDTA (20 mmol/L) solution whereafter 24-h urine was collected. Urinary 52Cr-EDTA concentrations were quantified using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Fecal Enterobacteriaceae and Faecalibacterium prausnitzii were quantified using FISH. Correlations between urinary 52Cr-EDTA excretion and other parameters were established using nonparametric Spearman's correlation coefficients (ρ). RESULTS: CD patients with increased fecal calprotectin levels (> 100 µg/g) demonstrated an elevated urinary 52Cr-EDTA/creatinine ratio (772 vs. 636 µmol/mol, P = 0.132). Patients with primarily colonic disease showed the highest 52Cr-EDTA excretion. Importantly, a positive correlation was observed for the urinary 52Cr-EDTA/creatinine ratio and fecal calprotectin levels (ρ = 0.325, P < 0.05). Finally, urinary 52Cr-EDTA/creatinine ratio negatively correlated with the relative abundance of Faecalibacterium prausnitzii (ρ = -0.221, P = 0.092), while positively correlating with Enterobacteriaceae (ρ = 0.202, P = 0.126). CONCLUSIONS: Orally administered and renal excreted 52Cr-EDTA may be used to assess intestinal permeability in CD and correlates with fecal calprotectin levels and bacterial species relevant to CD. This test may improve non-invasive detection of disease exacerbations and help monitor disease activity.


Assuntos
Doença de Crohn/urina , Disbiose/diagnóstico , Ácido Edético/administração & dosagem , Enterobacteriaceae/isolamento & purificação , Faecalibacterium prausnitzii/isolamento & purificação , Urina/química , Administração Oral , Adulto , Doença de Crohn/complicações , Doença de Crohn/metabolismo , Disbiose/metabolismo , Ácido Edético/química , Ácido Edético/farmacocinética , Enterobacteriaceae/genética , Faecalibacterium prausnitzii/genética , Fezes/química , Feminino , Humanos , Mucosa Intestinal/química , Complexo Antígeno L1 Leucocitário/metabolismo , Espectrometria de Massas , Pessoa de Meia-Idade , Participação do Paciente , Permeabilidade , Adulto Jovem
16.
Biosci Rep ; 39(6)2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31147456

RESUMO

Gut microbiota plays an important role in the regulation of the immune system and host's metabolism. We aimed to characterize the gut microbiota of Tunisian participants with and without diabetes.We enrolled ten participants with type 1 diabetes mellitus (T1DM), ten patients with type 2 diabetes mellitus (T2DM), and 11 subjects without diabetes. Bacteria was quantified in fecal samples by quantitative PCR (qPCR). Statistical tests and multivariate analysis were performed using RStudio program.Results showed that the proportions of Firmicutes, Akkermansia muciniphila, and Faecalibacterium prausnitzii (P≤0.041), as well as, the ratio Firmicutes/Bacteroidetes decreased in participants with T1DM compared with those without diabetes (p = 0.036). Participants with T2DM presented a reduction in the amounts of A. muciniphila and F. prausnitzii compared with those without diabetes (P≤0.036). Furthermore, A. muciniphila is negatively correlated with glucose level (P=0.022) and glycated hemoglobin (HbA1c) (P=0.035). Multivariate analysis revealed that participants with diabetes formed a cluster apart compared with those without diabetes.In conclusion the gut bacteria of Tunisian participants with diabetes was altered. The gut bacterial profile, especially the distribution of A muciniphila in participants with diabetes was affected by glycemic dysregulation. The investigation of the gut microbiota may help clinicians to improve diagnosis and treatment of diabetes and its complications.


Assuntos
Diabetes Mellitus Tipo 1/microbiologia , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal/genética , Trato Gastrointestinal/microbiologia , Adulto , Idoso , Akkermansia , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , Glicemia/genética , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Faecalibacterium prausnitzii/genética , Faecalibacterium prausnitzii/isolamento & purificação , Fezes/microbiologia , Feminino , Firmicutes/genética , Firmicutes/isolamento & purificação , Trato Gastrointestinal/patologia , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Tunísia/epidemiologia , Verrucomicrobia/genética , Verrucomicrobia/isolamento & purificação
17.
Artigo em Inglês | MEDLINE | ID: mdl-30245977

RESUMO

Akkermansia muciniphila and Faecalibacterium prausnitzii, cohabitants in the intestinal mucosa, are considered members of a healthy microbiota and reduction of both species occurs in several intestinal disorders, including inflammatory bowel disease. Little is known however about a possible link between the reduction in quantity of these species, and in which circumstances this may occur. This study aims to determine the abundances and co-occurrence of the two species in order to elucidate conditions that may compromise their presence in the gut. Loads of A. muciniphila, total F. prausnitzii and its two phylogroup (16S rRNA gene copies) were determined by quantitative polymerase chain reaction in colonic biopsies from 17 healthy controls (H), 23 patients with ulcerative colitis (UC), 31 patients with Crohn's disease (CD), 3 with irritable bowel syndrome (IBS) and 3 with colorectal cancer (CRC). Data were normalized to total bacterial 16S rRNA gene copies in the same sample. Prevalence, relative abundances and correlation analyses were performed according to type of disease and considering relevant clinical characteristics of patients such as IBD location, age of disease onset, CD behavior, current medication and activity status. Co-occurrence of both species was found in 29% of H, 65% of UC and 29% of CD. Lower levels of total F. prausnitzii and phylogroups were found in subjects with CD, compared with H subjects (P ≤ 0.044). In contrast, no differences were found with the regard to A. muciniphila abundance across different disease states, but CD patients with disease onset below 16 years of age featured a marked depletion of this species. In CD patients, correlation between A. muciniphila and total F. prausnitzii (ρ = 0.362, P = 0.045) was observed, and particularly in those with non-stricturing, non-penetrating disease behavior and under moderate immunosuppressants therapy. Altogether, this study revealed that co-occurrence of both species differs between disease status. In addition, IBD patients featured a reduction of F. prausnitzii but similar loads of A. muciniphila when compared to H subjects, with the exception of those with early onset CD. Depletion of A. muciniphila in this subgroup of subjects suggests that it could be a potential biomarker to assist in pediatric CD diagnosis.


Assuntos
Colo/microbiologia , Faecalibacterium prausnitzii/isolamento & purificação , Doenças Inflamatórias Intestinais/microbiologia , Mucosa Intestinal/microbiologia , Verrucomicrobia/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carga Bacteriana , Biópsia , Coinfecção/microbiologia , Feminino , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , RNA Ribossômico 16S/genética , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
18.
PLoS One ; 12(2): e0171352, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28187199

RESUMO

Physical exercise is a tool to prevent and treat some of the chronic diseases affecting the world's population. A mechanism through which exercise could exert beneficial effects in the body is by provoking alterations to the gut microbiota, an environmental factor that in recent years has been associated with numerous chronic diseases. Here we show that physical exercise performed by women to at least the degree recommended by the World Health Organization can modify the composition of gut microbiota. Using high-throughput sequencing of the 16s rRNA gene, eleven genera were found to be significantly different between active and sedentary women. Quantitative PCR analysis revealed higher abundance of health-promoting bacterial species in active women, including Faecalibacterium prausnitzii, Roseburia hominis and Akkermansia muciniphila. Moreover, body fat percentage, muscular mass and physical activity significantly correlated with several bacterial populations. In summary, we provide the first demonstration of interdependence between some bacterial genera and sedentary behavior parameters, and show that not only does the dose and type of exercise influence the composition of gut microbiota, but also the breaking of sedentary behavior.


Assuntos
Exercício Físico , Microbioma Gastrointestinal , Comportamento Sedentário , Adulto , Distribuição da Gordura Corporal , Clostridiales/isolamento & purificação , Faecalibacterium prausnitzii/isolamento & purificação , Feminino , Humanos , Verrucomicrobia/isolamento & purificação
19.
ISME J ; 11(4): 841-852, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28045459

RESUMO

There is an increasing interest in Faecalibacterium prausnitzii, one of the most abundant bacterial species found in the gut, given its potentially important role in promoting gut health. Although some studies have phenotypically characterized strains of this species, it remains a challenge to determine which factors have a key role in maintaining the abundance of this bacterium in the gut. Besides, phylogenetic analysis has shown that at least two different F. prausnitzii phylogroups can be found within this species and their distribution is different between healthy subjects and patients with gut disorders. It also remains unknown whether or not there are other phylogroups within this species, and also if other Faecalibacterium species exist. Finally, many studies have shown that F. prausnitzii abundance is reduced in different intestinal disorders. It has been proposed that F. prausnitzii monitoring may therefore serve as biomarker to assist in gut diseases diagnostics. In this mini-review, we aim to serve as an overview of F. prausnitzii phylogeny, ecophysiology and diversity. In addition, strategies to modulate the abundance of F. prausnitzii in the gut as well as its application as a biomarker for diagnostics and prognostics of gut diseases are discussed. This species may be a useful potential biomarker to assist in ulcerative colitis and Crohn's disease discrimination.


Assuntos
Faecalibacterium prausnitzii/isolamento & purificação , Biomarcadores , Faecalibacterium prausnitzii/genética , Gastroenteropatias/microbiologia , Humanos , Filogenia
20.
PLoS One ; 12(1): e0170589, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28125651

RESUMO

Meningoencephalomyelitis of unknown origin (MUO) is a common, naturally-occurring, clinical disease of pet dogs. It is an immune-mediated condition that has many similarities with experimental autoimmune encephalitis (EAE) in rodents and so investigation of its pathogenesis may aid in understanding factors that contribute to development of multiple sclerosis in people. Gut microbiota are known to modulate immune responses that influence susceptibility to immune-mediated brain disease. In this study we aimed to compare abundance of specific constituents of the fecal microbiota, namely Faecalibacterium prausnitzii and Prevotellaceae, between dogs diagnosed with MUO and matched controls. Fecal samples were obtained from 20 dogs diagnosed with MUO and 20 control dogs matched for breed, age and gender. Bacterial abundance was measured using qPCR and 16S rRNA sequencing. We found that Prevotellaceae were significantly less abundant in cases compared with controls (p = 0.003) but there was no difference in abundance of F.prausnitzii. There was no evidence of other differences in gut microbiota between groups. These data, derived from this naturally-occurring canine clinical model, provide strong corroborative evidence that high abundance of Prevotellaceae in the gut is associated with reduced risk for developing immune-mediated brain disease.


Assuntos
Bacteroidetes/isolamento & purificação , Encefalopatias/microbiologia , Doenças do Cão/microbiologia , Microbiota/genética , Animais , Bacteroidetes/genética , Bacteroidetes/patogenicidade , Encefalopatias/diagnóstico , Encefalopatias/genética , Encefalopatias/patologia , DNA Bacteriano/genética , Doenças do Cão/diagnóstico , Doenças do Cão/genética , Doenças do Cão/patologia , Cães , Faecalibacterium prausnitzii/genética , Faecalibacterium prausnitzii/isolamento & purificação , Faecalibacterium prausnitzii/patogenicidade , Fezes/microbiologia , Trato Gastrointestinal/microbiologia , RNA Ribossômico 16S/genética
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