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1.
Am J Gastroenterol ; 115(2): 190-201, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31913194

RESUMO

INTRODUCTION: We conducted a systematic review and meta-analysis to compare the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with irritable bowel syndrome (IBS) and controls. METHODS: Electronic databases were searched up to December 2018 for studies reporting SIBO prevalence in patients with IBS. Prevalence rates, odds ratios (ORs), and 95% confidence intervals (CIs) of SIBO in patients with IBS and controls were calculated. RESULTS: We included 25 studies with 3,192 patients with IBS and 3,320 controls. SIBO prevalence in patients with IBS was significantly increased compared with controls (OR = 3.7, 95% CI 2.3-6.0). In studies using only healthy controls, the OR for SIBO in patients with IBS was 4.9 (95% CI 2.8-8.6). With breath testing, SIBO prevalence in patients with IBS was 35.5% (95% CI 33.6-37.4) vs 29.7% (95% CI 27.6-31.8) in controls. Culture-based studies yielded a SIBO prevalence of 13.9% (95% CI 11.5-16.4) in patients with IBS and 5.0% (95% CI 3.9-6.2) in controls with a cutoff value of 10 colony-forming units per milliliter vs 33.5% (95% CI 30.1-36.9) in patients with IBS and 8.2% (95% CI 6.8-9.6) in controls with a cutoff value of 10 colony-forming unit per milliliter, respectively. SIBO prevalence diagnosed by lactulose breath test is much greater in both patients with IBS (3.6-fold) and controls (7.6-fold) compared with glucose breath test. Similar difference is seen when lactulose breath test is compared with culture methods. OR for SIBO in patients with IBS-diarrhea compared with IBS-constipation was 1.86 (95% CI 1.83-2.8). Methane-positive breath tests were significantly more prevalent in IBS-constipation compared with IBS-diarrhea (OR = 2.3, 95% CI 1.2-4.2). In patients with IBS, proton pump inhibitor was not associated with SIBO (OR = 0.8, 95% CI 0.5-1.5, P = 0.55). DISCUSSION: This systematic review and meta-analysis suggests a link between IBS and SIBO. However, the overall quality of the evidence is low. This is mainly due to substantial "clinical heterogeneity" due to lack of uniform selection criteria for cases and controls and limited sensitivity and specificity of the available diagnostic tests.

2.
Ann Rheum Dis ; 79(1): 132-140, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31662318

RESUMO

OBJECTIVES: Diverse evidence including clinical, genetic and microbiome studies support a major role of the gut microbiome in the common immune-mediated arthropathy, ankylosing spondylitis (AS). We set out to (1) further define the key microbial characteristics driving disease, and (2) examine the effects of tumour necrosis factor-inhibitor (TNFi) therapy upon the microbiome. METHODS: The stools from a case-control cohort of 250 Han-Chinese subjects underwent shotgun metagenomic sequencing. All subjects were genotyped using the Illumina CoreExome SNP microarray. RESULTS: Previous reports of gut dysbiosis in AS were reconfirmed and several notable bacterial species and functional categories were differentially abundant. TNFi therapy was correlated with a restoration the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. Enrichment of bacterial peptides homologous to HLA-B27-presented epitopes was observed in the stools of patients with AS, suggesting that either HLA-B27 fails to clear these or that they are involved in driving HLA-B27-associated immune reactions. TNFi therapy largely restored the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. TNFi therapy of patients with AS was also associated with a reduction of potentially arthritogenic bacterial peptides, relative to untreated patients. CONCLUSION: These findings emphasise the key role that the gut microbiome plays in driving the pathogenesis of AS and highlight potential therapeutic and/or preventative targets.

3.
Nephrology (Carlton) ; 25(1): 5-13, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31587409

RESUMO

Infectious complications are common following kidney transplantation and rank in the top five causes of death in patients with allograft function. Over the last 5 years, there has been emerging evidence that changes in the gastrointestinal microbiota following kidney transplantation may play a key role in the pathogenesis of transplant-associated infections. Different factors have emerged which may disrupt the interaction between the gastrointestinal microbiota and the immune system, which may lead to infective complications in kidney transplant recipients. Over the last 5 years, there has been emerging evidence that changes in the gastrointestinal microbiota following kidney transplantation may play a key role in the pathogenesis of transplant-associated infections. This review will discuss the structure and function of the gastrointestinal microbiota, the changes that occur in the gastrointestinal microbiota following kidney transplantation and the factors underpinning these changes, how these changes may lead to transplant-associated infectious complications and potential treatments which may be instituted to mitigate this risk.

4.
Medicina (Kaunas) ; 55(10)2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31590269

RESUMO

The incidence of infectious complications, compared with the general population and the pre-transplant status of the recipient, increases substantially following kidney transplantation, causing significant morbidity and mortality. The potent immunosuppressive therapy given to prevent graft rejection in kidney transplant recipients results in an increased susceptibility to a wide range of opportunistic infections including bacterial, viral and fungal infections. Over the last five years, several advances have occurred that may have changed the burden of infectious complications in kidney transplant recipients. Due to the availability of direct-acting antivirals to manage donor-derived hepatitis C infection, this has opened the way for donors with hepatitis C infection to be considered in the donation process. In addition, there have been the development of medications targeting the growing burden of resistant cytomegalovirus, as well as the discovery of the potentially important role of the gastrointestinal microbiota in the pathogenesis of post-transplant infection. In this narrative review, we will discuss these three advances and their potential implications for clinical practice.

5.
J Pediatr Gastroenterol Nutr ; 69(6): 726-732, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31568152

RESUMO

OBJECTIVES: This study aimed to explore the associations between food group intake, faecal microbiota profile, and body composition during the period of complementary feeding. METHODS: Diet was assessed using a quantitative food frequency questionnaire, faecal microbiota profile was assessed using 16S rRNA gene sequencing, and body composition was assessed using bioelectrical impedance analysis and dual energy x-ray absorptiometry, in a cohort of 50 infants aged 6 to 24 months of age. RESULTS: During this critical period of microbiota development, age was the strongest predictor of microbiota composition with network analysis revealing a cluster of genera positively associated with age. A separate cluster comprised genera associated with fat mass index with Bifidobacterium showing the strongest correlation with fat mass index (rho = 0.55, P = 0.001, false discovery rate [FDR] = 0.018). Dairy intake was both negatively correlated with Bacteroides (rho = -0.49, P < 0.001, FDR = 0.024) and positively correlated with lean mass index (rho = 0.44, P = 0.007, FDR = 0.024). Antibiotics use in the first month of life had the most striking influence on body composition and was associated with an increase in mean body mass index z score of 1.17 (P = 0.001) and body fat of 3.5% (P = 0.001). CONCLUSIONS: Our results suggested that antibiotics use in the first month of life had the most striking influence on body composition in this cohort of infants aged 6 to 24 months, whereas dairy intake interacted with both microbiota and body composition in early life.

6.
Aging Cell ; 18(5): e13014, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31373126

RESUMO

The mechanistic target of rapamycin (mTOR) is an evolutionarily conserved protein kinase that regulates growth and metabolism. mTOR is found in two protein complexes, mTORC1 and mTORC2, that have distinct components and substrates and are both inhibited by rapamycin, a macrolide drug that robustly extends lifespan in multiple species including worms and mice. Although the beneficial effect of rapamycin on longevity is generally attributed to reduced mTORC1 signaling, disruption of mTORC2 signaling can also influence the longevity of worms, either positively or negatively depending on the temperature and food source. Here, we show that loss of hypothalamic mTORC2 signaling in mice decreases activity level, increases the set point for adiposity, and renders the animals susceptible to diet-induced obesity. Hypothalamic mTORC2 signaling normally increases with age, and mice lacking this pathway display higher fat mass and impaired glucose homeostasis throughout life, become more frail with age, and have decreased overall survival. We conclude that hypothalamic mTORC2 is essential for the normal metabolic health, fitness, and lifespan of mice. Our results have implications for the use of mTORC2-inhibiting pharmaceuticals in the treatment of brain cancer and diseases of aging.

7.
Sci Rep ; 9(1): 12476, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462648

RESUMO

Early life nutrition is a vital determinant of an individual's life-long health and also directly influences the ecological and functional development of the gut microbiota. However, there are limited longitudinal studies examining the effect of diet on the gut microbiota development in early childhood. Here, up to seven stool samples were collected from each of 48 healthy children during their second year of life, and microbiota dynamics were assessed using 16S rRNA gene amplicon sequencing. Children's dietary information was also collected during the same period using a validated food frequency questionnaire designed for this age group, over five time points. We observed significant changes in gut microbiota community, concordant with changes in the children's dietary pattern over the 12-month period. In particular, we found differential effects on specific Firmicutes-affiliated lineages in response to frequent intake of either processed or unprocessed foods. Additionally, the consumption of fortified milk supplemented with a Bifidobacterium probiotic and prebiotics (synbiotics) further increased the presence of Bifidobacterium spp., highlighting the potential use of synbiotics to prolong and sustain changes in these lineages and shaping the gut microbiota community in young children.

8.
Clin Transl Gastroenterol ; 10(8): e00068, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31373933

RESUMO

OBJECTIVES: Chronic liver disease (CLD) is associated with both alterations of the stool microbiota and increased small intestinal permeability. However, little is known about the role of the small intestinal mucosa-associated microbiota (MAM) in CLD. The aim of this study was to evaluate the relationship between the duodenal MAM and both small intestinal permeability and liver disease severity in CLD. METHODS: Subjects with CLD and a disease-free control group undergoing routine endoscopy underwent duodenal biopsy to assess duodenal MAM by 16S rRNA gene sequencing. Small intestinal permeability was assessed by a dual sugar (lactulose: rhamnose) assay. Other assessments included transient elastography, endotoxemia, serum markers of hepatic inflammation, dietary intake, and anthropometric measurements. RESULTS: Forty-six subjects (35 with CLD and 11 controls) were assessed. In subjects with CLD, the composition (P = 0.02) and diversity (P < 0.01) of the duodenal MAM differed to controls. Constrained multivariate analysis and linear discriminate effect size showed this was due to Streptococcus-affiliated lineages. Small intestinal permeability was significantly higher in CLD subjects compared to controls. In CLD, there were inverse correlations between microbial diversity and both increased small intestinal permeability (r = -0.41, P = 0.02) and serum alanine aminotransferase (r = -0.35, P = 0.04). Hepatic stiffness was not associated with the MAM. DISCUSSION: In CLD, there is dysbiosis of the duodenal MAM and an inverse correlation between microbial diversity and small intestinal permeability. TRANSLATIONAL IMPACT: Strategies to ameliorate duodenal MAM dysbiosis may ameliorate intestinal barrier dysfunction and liver injury in CLD.

9.
Semin Liver Dis ; 39(4): 432-441, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31315136

RESUMO

The authors conducted a systematic review and meta-analysis to assess the effect of antibiotic therapy in primary sclerosing cholangitis (PSC). Effect of antibiotic therapy on Mayo PSC Risk Score (MRS), serum alkaline phosphatase (ALP), total serum bilirubin (TSB), and adverse events (AEs) rates were calculated and expressed as standardized difference of means or proportions. Five studies including 124 PSC patients who received antibiotics were included. Overall, antibiotic treatment was associated with a statistically significant reduction in ALP, MRS, and TSB by 33.2, 36.1, and 28.8%, respectively. ALP reduction was greatest for vancomycin (65.6%, p < 0.002) and smallest with metronidazole (22.7%, p = 0.18). Overall, 8.9% (95% confidence interval: 3.9-13.9) of patients had AEs severe enough to discontinue antibiotic therapy. In PSC patients, antibiotic treatment results in a significant improvement in markers of cholestasis and MRS. Antibiotics, particularly vancomycin, may have a positive effect on PSC either via direct effects on the microbiome or via host-mediated mechanisms.

10.
Proc Natl Acad Sci U S A ; 116(12): 5613-5622, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30842288

RESUMO

Many microbes acquire metabolites in a "feeding" process where complex polymers are broken down in the environment to their subunits. The subsequent uptake of soluble metabolites by a cell, sometimes called osmotrophy, is facilitated by transporter proteins. As such, the diversification of osmotrophic microorganisms is closely tied to the diversification of transporter functions. Horizontal gene transfer (HGT) has been suggested to produce genetic variation that can lead to adaptation, allowing lineages to acquire traits and expand niche ranges. Transporter genes often encode single-gene phenotypes and tend to have low protein-protein interaction complexity and, as such, are potential candidates for HGT. Here we test the idea that HGT has underpinned the expansion of metabolic potential and substrate utilization via transfer of transporter-encoding genes. Using phylogenomics, we identify seven cases of transporter-gene HGT between fungal phyla, and investigate compatibility, localization, function, and fitness consequences when these genes are expressed in Saccharomyces cerevisiae Using this approach, we demonstrate that the transporters identified can alter how fungi utilize a range of metabolites, including peptides, polyols, and sugars. We then show, for one model gene, that transporter gene acquisition by HGT can significantly alter the fitness landscape of S. cerevisiae We therefore provide evidence that transporter HGT occurs between fungi, alters how fungi can acquire metabolites, and can drive gain in fitness. We propose a "transporter-gene acquisition ratchet," where transporter repertoires are continually augmented by duplication, HGT, and differential loss, collectively acting to overwrite, fine-tune, and diversify the complement of transporters present in a genome.


Assuntos
Transferência Genética Horizontal/genética , Aptidão Genética/genética , Saccharomyces cerevisiae/genética , Evolução Biológica , Evolução Molecular , Fungos/genética , Genoma , Proteínas de Membrana Transportadoras/genética , Fenótipo , Filogenia , Proteínas de Saccharomyces cerevisiae/genética
11.
Nutrients ; 11(3)2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30871219

RESUMO

Although the oral microbiota is known to play a crucial role in human health, there are few studies of diet x oral microbiota interactions, and none in elite athletes who may manipulate their intakes of macronutrients to achieve different metabolic adaptations in pursuit of optimal endurance performance. The aim of this study was to investigate the shifts in the oral microbiome of elite male endurance race walkers from Europe, Asia, the Americas and Australia, in response to one of three dietary patterns often used by athletes during a period of intensified training: a High Carbohydrate (HCHO; n = 9; with 60% energy intake from carbohydrates; ~8.5 g kg-1 day-1 carbohydrate, ~2.1 g kg-1 day-1 protein, 1.2 g kg-1 day-1 fat) diet, a Periodised Carbohydrate (PCHO; n = 10; same macronutrient composition as HCHO, but the intake of carbohydrates is different across the day and throughout the week to support training sessions with high or low carbohydrate availability) diet or a ketogenic Low Carbohydrate High Fat (LCHF; n = 10; 0.5 g kg-1 day-1 carbohydrate; 78% energy as fat; 2.1 g kg-1 day-1 protein) diet. Saliva samples were collected both before (Baseline; BL) and after the three-week period (Post treatment; PT) and the oral microbiota profiles for each athlete were produced by 16S rRNA gene amplicon sequencing. Principal coordinates analysis of the oral microbiota profiles based on the weighted UniFrac distance measure did not reveal any specific clustering with respect to diet or athlete ethnic origin, either at baseline (BL) or following the diet-training period. However, discriminant analyses of the oral microbiota profiles by Linear Discriminant Analysis (LDA) Effect Size (LEfSe) and sparse Partial Least Squares Discriminant Analysis (sPLS-DA) did reveal changes in the relative abundance of specific bacterial taxa, and, particularly, when comparing the microbiota profiles following consumption of the carbohydrate-based diets with the LCHF diet. These analyses showed that following consumption of the LCHF diet the relative abundances of Haemophilus, Neisseria and Prevotella spp. were decreased, and the relative abundance of Streptococcus spp. was increased. Such findings suggest that diet, and, in particular, the LCHF diet can induce changes in the oral microbiota of elite endurance walkers.


Assuntos
Bactérias/classificação , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Boca/microbiologia , Resistência Física , Caminhada , Adulto , Humanos , Masculino , Estado Nutricional , Condicionamento Físico Humano , Esportes , Adulto Jovem
12.
Aliment Pharmacol Ther ; 49(6): 624-635, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30735254

RESUMO

BACKGROUND: Current data on small intestinal bacterial overgrowth (SIBO) in patients with inflammatory bowel diseases (IBD) are controversial. AIM: To conduct a systematic review and meta-analysis to determine the prevalence of SIBO in patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Electronic databases were searched up to May 2018 for studies reporting prevalence of SIBO in IBD patients. The prevalence rate of SIBO among IBD patients and the odds ratio (OR) and 95% CI of SIBO in IBD patients compared with controls were calculated. RESULTS: The final dataset included 11 studies (1175 adult patients with IBD and 407 controls), all utilising breath test for diagnosis of SIBO. The proportion of SIBO in IBD patients was 22.3% (95% CI 19.92-24.68). The OR for SIBO in IBD patients was 9.51 (95% CI 3.39-26.68) compared to non-IBD controls, and high in both CD (OR = 10.86; 95% CI 2.76-42.69) and UC (OR = 7.96; 95% CI 1.66-38.35). In patients with CD, subgroup analysis showed the presence of fibrostenosing disease (OR = 7.47; 95% CI 2.51-22.20) and prior bowel surgery (OR = 2.38; 95% CI 1.65-3.44), especially resection of the ileocecal valve, increased the odds of SIBO. Individual studies suggest that combined small and large bowel disease but not disease activity may be associated with SIBO. CONCLUSIONS: Overall, there is a substantial increase in the prevalence of SIBO in IBD patients compared to controls. Prior surgery and the presence of fibrostenosing disease are risk factors for SIBO in IBD.

13.
Nutrients ; 11(2)2019 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-30682843

RESUMO

We investigated extreme changes in diet patterns on the gut microbiota of elite race walkers undertaking intensified training and its possible links with athlete performance. Numerous studies with sedentary subjects have shown that diet and/or exercise can exert strong selective pressures on the gut microbiota. Similar studies with elite athletes are relatively scant, despite the recognition that diet is an important contributor to sports performance. In this study, stool samples were collected from the cohort at the beginning (baseline; BL) and end (post-treatment; PT) of a three-week intensified training program during which athletes were assigned to a High Carbohydrate (HCHO), Periodised Carbohydrate (PCHO) or ketogenic Low Carbohydrate High Fat (LCHF) diet (post treatment). Microbial community profiles were determined by 16S rRNA gene amplicon sequencing. The microbiota profiles at BL could be separated into distinct "enterotypes," with either a Prevotella or Bacteroides dominated enterotype. While enterotypes were relatively stable and remained evident post treatment, the LCHF diet resulted in a greater relative abundance of Bacteroides and Dorea and a reduction of Faecalibacterium. Significant negative correlations were observed between Bacteroides and fat oxidation and between Dorea and economy test following LCHF intervention.


Assuntos
Dieta com Restrição de Carboidratos , Dieta Hiperlipídica , Fezes/microbiologia , Microbioma Gastrointestinal/fisiologia , Caminhada/fisiologia , Adulto , Atletas , Humanos , Análise de Componente Principal , Adulto Jovem
14.
Diabetes Care ; 42(3): 364-371, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30659070

RESUMO

OBJECTIVE: Given the role of gut microbiota in regulating metabolism, probiotics administered during pregnancy might prevent gestational diabetes mellitus (GDM). This question has not previously been studied in high-risk overweight and obese pregnant women. We aimed to determine whether probiotics (Lactobacillus rhamnosus and Bifidobacterium animalis subspecies lactis) administered from the second trimester in overweight and obese women prevent GDM as assessed by an oral glucose tolerance test (OGTT) at 28 weeks' gestation. Secondary outcomes included maternal and neonatal complications, maternal blood pressure and BMI, and infant body composition. RESEARCH DESIGN AND METHODS: This was a double-blind randomized controlled trial of probiotic versus placebo in overweight and obese pregnant women in Brisbane, Australia. RESULTS: The study was completed in 411 women. GDM occurred in 12.3% (25 of 204) in the placebo arm and 18.4% (38 of 207) in the probiotics arm (P = 0.10). At OGTT, mean fasting glucose was higher in women randomized to probiotics (79.3 mg/dL) compared with placebo (77.5 mg/dL) (P = 0.049). One- and two-hour glucose measures were similar. Preeclampsia occurred in 9.2% of women randomized to probiotics compared with 4.9% in the placebo arm (P = 0.09). Excessive weight gain occurred in 32.5% of women in the probiotics arm (55 of 169) compared with 46% in the placebo arm (81 of 176) (P = 0.01). Rates of small for gestational age (<10th percentile) were 2.4% in the probiotics arm (5 of 205) and 6.5% in the placebo arm (13 of 199) (P = 0.042). There were no differences in other secondary outcomes. CONCLUSIONS: The probiotics used in this study did not prevent GDM in overweight and obese pregnant women.


Assuntos
Diabetes Gestacional/prevenção & controle , Obesidade/dietoterapia , Sobrepeso/dietoterapia , Complicações na Gravidez/dietoterapia , Probióticos/uso terapêutico , Adulto , Austrália , Diabetes Gestacional/sangue , Método Duplo-Cego , Feminino , Microbioma Gastrointestinal , Teste de Tolerância a Glucose , Humanos , Obesidade/complicações , Sobrepeso/complicações , Gravidez , Ganho de Peso
15.
Eur J Nutr ; 58(7): 2895-2910, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30324342

RESUMO

PURPOSE: Variation in the human microbiome has been linked with a variety of physiological functions, including immune regulation and metabolism and biosynthesis of vitamins, hormones, and neurotransmitters. Evidence for extraskeletal effects of vitamin D has been accruing and it has been suggested that the effect of vitamin D on health is partially mediated through the microbiome. We aimed to critically evaluate the evidence linking vitamin D and the gastrointestinal microbiome. METHODS: We systematically searched the Embase, Web of Science, PubMed and CINAHL databases, including peer-reviewed publications that reported an association between a measure of vitamin D and the gastrointestinal microbiome in humans or experimental animals. RESULTS: We included 10 mouse and 14 human studies. Mouse studies compared mice fed diets containing different levels of vitamin D (usually high versus low), or vitamin D receptor knockout or Cyp27B1 knockout with wild-type mice. Five mouse studies reported an increase in Bacteroidetes (or taxa within that phylum) in the low vitamin D diet or gene knockout group. Human studies were predominantly observational; all but two of the included studies found some association between vitamin D and the gut microbiome, but the nature of differences observed varied across studies. CONCLUSIONS: Despite substantial heterogeneity, we found evidence to support the hypothesis that vitamin D influences the composition of the gastrointestinal microbiome. However, the research is limited, having been conducted either in mice or in mostly small, selected human populations. Future research in larger population-based studies is needed to fully understand the extent to which vitamin D modulates the microbiome.

17.
Curr Treat Options Gastroenterol ; 16(4): 591-604, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30421297

RESUMO

PURPOSE OF REVIEW: Like the rest of the gastrointestinal tract, the small intestine is colonised by microbes, but how this "microbiome" affects the immune system and digestive functions has largely been overlooked, especially in the "omics" era. Here, we present recent findings that show that the diversity, density and interactions of these microbes in the small intestine can play an important role in the pathogenesis of a number of gastrointestinal and extraintestinal disorders. RECENT FINDINGS: Changes in the small intestinal mucosa-associated microbiota (SI-MAM) have been shown to occur with inflammatory bowel diseases, functional gastrointestinal disorders, metabolic disorders such as obesity and type 2 diabetes. More recently, there is emerging evidence that small intestinal dysbiosis can be a driver for the progression of chronic liver disease. Initially believed that small intestinal dysbiosis (e.g. SIBO) is mainly due to alterations of luminal conditions (e.g. after surgical resections of the ileocecal valve), there is now enough evidence to conclude that small intestinal dysbiosis can occur without underlying structural abnormalities. Alterations of the SI-MAM appear to play a key role for the manifestation and progression of inflammatory and metabolic disorders.

18.
mBio ; 9(5)2018 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-30301852

RESUMO

Cutaneous squamous cell carcinoma (SCC) is the second-most-common cancer in Australia. The majority of SCCs progress from premalignant actinic keratosis (AK) lesions that form on chronically sun-exposed skin. The role of skin microbiota in this progression is not well understood; therefore, we performed a longitudinal microbiome analysis of AKs and SCCs using a cohort of 13 SCC-prone immunocompetent men. The majority of variability in microbial profiles was attributable to subject, followed by time and lesion type. Propionibacterium and Malassezia organisms were relatively more abundant in nonlesional photodamaged skin than in AKs and SCCs. Staphylococcus was most commonly associated with lesional skin, in particular, sequences most closely related to Staphylococcus aureus Of 11 S. aureus-like operational taxonomic units (OTUs), six were significantly associated with SCC lesions across seven subjects, suggesting their specific involvement with AK-to-SCC progression. If a causative link exists between certain S. aureus-like OTUs and SCC etiology, therapeutic approaches specifically targeting these bacteria could be used to reduce SCC.IMPORTANCE Actinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC) are two of the most common dermatologic conditions in Western countries and cause substantial morbidity worldwide. The role of human papillomaviruses under these conditions has been well studied yet remains inconclusive. One PCR-based study has investigated bacteria in the etiology of these conditions; however, no study has investigated the microbiomes of AK and SCC more broadly. We longitudinally profiled the microbiomes of 112 AK lesions, profiled cross sections of 32 spontaneously arising SCC lesions, and compared these to matching nonlesional photodamaged control skin sites. We identified commonly occurring strains of Propionibacterium and Malassezia at higher relative abundances on nonlesional skin than in AK and SCC lesions, and strains of Staphylococcus aureus were relatively more abundant in lesional than nonlesional skin. These findings may aid in the prevention of SCC.


Assuntos
Bactérias/isolamento & purificação , Carcinoma de Células Escamosas/microbiologia , Ceratose Actínica/microbiologia , Microbiota , Neoplasias Cutâneas/microbiologia , Idoso , Idoso de 80 Anos ou mais , Bactérias/genética , Progressão da Doença , Humanos , Imunocompetência , Estudos Longitudinais , Malassezia/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Propionibacterium/isolamento & purificação , RNA Ribossômico 16S/genética , Pele/microbiologia , Pele/patologia , Pele/efeitos da radiação , Staphylococcus aureus/isolamento & purificação
19.
ISME J ; 12(12): 2942-2953, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30068938

RESUMO

The genus Methanosphaera is a well-recognized but poorly characterized member of the mammalian gut microbiome, and distinctive from Methanobrevibacter smithii for its ability to induce a pro-inflammatory response in humans. Here we have used a combination of culture- and metagenomics-based approaches to expand the representation and information for the genus, which has supported the examination of their phylogeny and physiological capacity. Novel isolates of the genus Methanosphaera were recovered from bovine rumen digesta and human stool, with the bovine isolate remarkable for its large genome size relative to other Methanosphaera isolates from monogastric hosts. To substantiate this observation, we then recovered seven high-quality Methanosphaera-affiliated population genomes from ruminant and human gut metagenomic datasets. Our analyses confirm a monophyletic origin of Methanosphaera spp. and that the colonization of monogastric and ruminant hosts favors representatives of the genus with different genome sizes, reflecting differences in the genome content needed to persist in these different habitats.


Assuntos
Microbioma Gastrointestinal , Tamanho do Genoma/genética , Metagenômica , Methanobacteriaceae/genética , Animais , Bovinos , Fezes/microbiologia , Humanos , Methanobacteriaceae/fisiologia , Methanobrevibacter/genética , Methanobrevibacter/fisiologia , Filogenia , Rúmen/microbiologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-30123780

RESUMO

The oral microbiome can play a role in the instigation and progression of oral diseases that can manifest into other systemic conditions. These associations encourage the exploration of oral dysbiosis leading to the pathogenesis of cancers. In this study, oral rinse was used to characterize the oral microbiome fluctuation associated with oral cavity cancer (OCC) and oropharyngeal cancers (OPC). The study cohort consists of normal healthy controls (n = 10, between 20 and 30 years of age; n = 10, above 50 years of age), high-risk individuals (n = 11, above 50 years of age with bad oral hygiene and/or oral diseases) and OCC and OPC patients (n = 31, HPV-positive; n = 21, HPV-negative). Oral rinse samples were analyzed using 16S rRNA gene amplicon sequencing on the MiSeq platform. Kruskal-Wallis rank test was used to identify genera associated with OCC and OPC. A logistic regression analysis was carried out to determine the performance of these genera as a biomarker panel to predict OCC and OPC. In addition, a two-fold cross-validation with a bootstrap procedure was carried out in R to investigate how well the panel would perform in an emulated clinical scenario. Our data indicate that the oral microbiome is able to predict the presence of OCC and OPC with sensitivity and specificity of 100 and 90%, respectively. With further validation, the panel could potentially be implemented into clinical diagnostic and prognostic workflows for OCC and OPC.


Assuntos
Bactérias/classificação , Biomarcadores Tumorais/análise , Microbiota , Neoplasias Bucais/microbiologia , Boca/microbiologia , Neoplasias Orofaríngeas/microbiologia , Bactérias/genética , Análise por Conglomerados , DNA Ribossômico/química , DNA Ribossômico/genética , Disbiose/complicações , Humanos , Neoplasias Bucais/diagnóstico , Neoplasias Orofaríngeas/diagnóstico , Filogenia , RNA Ribossômico 16S/genética , Sensibilidade e Especificidade , Análise de Sequência de DNA
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