RESUMO
OBJECTIVE: The aim of the study was to determine the mucosal microbiota associated with eosinophilic esophagitis (EoE) and eosinophilic gastritis (EoG) in a geographically diverse cohort of patients compared to controls. METHODS: We conducted a prospective study of individuals with eosinophilic gastrointestinal disease (EGID) in the Consortium of Eosinophilic Gastrointestinal Disease Researchers, including pediatric and adult tertiary care centers. Eligible individuals had clinical data, mucosal biopsies, and stool collected. Total bacterial load was determined from mucosal biopsy samples by quantitative polymerase chain reaction (PCR). Community composition was determined by small subunit rRNA gene amplicons. RESULTS: One hundred thirty-nine mucosal biopsies were evaluated corresponding to 93 EoE, 17 EoG, and 29 control specimens (18 esophageal) from 10 sites across the United States. Dominant community members across disease activity differed significantly. When comparing EoE and EoG with controls, the dominant taxa in individuals with EGIDs was increased ( Streptococcus in esophagus; Prevotella in stomach). Specific taxa were associated with active disease for both EoE ( Streptococcus , Gemella ) and EoG ( Leptotrichia ), although highly individualized communities likely impacted statistical testing. Alpha diversity metrics were similar across groups, but with high variability among individuals. Stool analyses did not correlate with bacterial communities found in mucosal biopsy samples and was similar in patients and controls. CONCLUSIONS: Dominant community members ( Streptococcus for EoE, Prevotella for EoG) were different in the mucosal biopsies but not stool of individuals with EGIDs compared to controls; taxa associated with EGIDs were highly variable across individuals. Further study is needed to determine if therapeutic interventions contribute to the observed community differences.
Assuntos
Esofagite Eosinofílica , Microbiota , Adulto , Humanos , Criança , Esofagite Eosinofílica/patologia , Estudos ProspectivosRESUMO
BACKGROUND: Acid blockade is commonly prescribed in patients with cystic fibrosis (CF). Growing concerns, however, exist about its possible role in the pathophysiology of pulmonary infections. We aimed to investigate if acid blockade alters esophageal and respiratory microbiota leading to dysbiosis and inflammation. METHODS: We performed a cross sectional study of children with CF who were either prescribed acid blockade or not. Samples from the gastrointestinal and respiratory tracts were obtained and microbiome analyzed. Mixed effect models were used to compare outcomes between cohorts and across sampling sites. A random subject intercept was included to account for the multiple sampling sites per individual. RESULTS: A cohort of 25 individuals, 44% girls with median age of 13.8 years [IQR 11.2--14.8] were enrolled. Alpha diversity, total bacterial load, and beta diversity were similar across anatomic compartments, across the upper gastrointestinal tract, and in respiratory samples. Similar alpha diversity, total bacterial load, and beta diversity results were also observed when comparing individuals on versus those off acid blockade. IL-8 was elevated in the distal versus proximal esophagus in the whole cohort (Pâ<â0.01). IL-8 concentrations were similar in the distal esophagus in patients on and off acid blockade, but significantly greater in the proximal esophagus of subjects on treatment (Pâ<â0.01). CONCLUSIONS: On the basis of these data, acid blockade use does not appear to influence the microbiome of the aerodigestive tract in children with cystic fibrosis suggesting a complex interplay between these medications and the bacterial composition of the esophagus and lung.
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Fibrose Cística , Microbiota , Adolescente , Bactérias , Criança , Estudos Transversais , Fibrose Cística/tratamento farmacológico , Disbiose , Feminino , Humanos , MasculinoRESUMO
Hyperuricemia is highly prevalent and especially common in subjects with metabolic, cardiovascular and renal diseases. In chronic kidney disease, hyperuricemia is extremely common, and uric acid (UA) excretion relies on gut uricolysis by gut microbiota. Current therapy for lowering serum UA includes drugs that may produce undesired secondary effects. Therefore, this pilot study was designed to evaluate the potential of two probiotic supplements to reduce systemic uric acid concentrations. Secondary objectives were to assess whether the hypouricemic effect related to a therapeutic benefit on the hyperuricemia-induced renal damage and hypertension. Analysis of fecal microbiota was also performed. Groups of 6 rats each were followed for 5 weeks and allocated in the following treatment groups: C = Control; HU-ND = Oxonic acid-induced hyperuricemia (HU) +regular diet; HU-P = HU+placebo; HU-F1 = HU+ probiotics formula 1 and HU-F2 = HU+ probiotics formula 2. We confirmed that oxonic acid-induced hyperuricemia produced hypertension and renal functional and structural changes, along with modest changes in the overall composition of fecal microbiota. Both probiotic-containing diets prevented HU, elevated UA urinary excretion and intrarenal UA accumulation induced by oxonic acid. The hypouricemic effect conferred by probiotic supplementation also prevented the renal changes and hypertension caused by hyperuricemia. However, probiotic treatment did not restore the fecal microbiota. In conclusion, we demonstrated for the first time the ability of probiotics containing uricolytic bacteria to lower serum uric acid in hyperuricemic animals with beneficial consequences on blood pressure and renal disease. As probiotics supplements are innocuous for human health, we recommend clinical studies to test if probiotic supplements could benefit hyperuricemic individuals.
Assuntos
Suplementos Nutricionais , Hiperuricemia/induzido quimicamente , Hiperuricemia/prevenção & controle , Rim/efeitos dos fármacos , Rim/lesões , Ácido Oxônico/efeitos adversos , Probióticos/farmacologia , Animais , Citoproteção/efeitos dos fármacos , Relação Dose-Resposta a Droga , Hiperuricemia/metabolismo , Hiperuricemia/patologia , Rim/metabolismo , Rim/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Projetos Piloto , Ratos , Ratos Wistar , Ácido Úrico/metabolismoRESUMO
BACKGROUND: Chronic rhinosinusitis (CRS) is a multifactorial inflammatory airway disorder in which bacteria are implicated in the initiation and/or sustenance of disease in some patients. The sinuses are colonized by bacteria even in health, and the potential for sinus-specific niches harboring unique microbial consortia raises questions for clinical and research investigation. The objective was to determine the degree to which resident upper airways microbiota differ between individuals and anatomic sites, in order to determine the optimal site of microbial sampling for study in CRS. METHODS: Eight CRS patients undergoing primary surgery were sampled bilaterally at the anterior nares, middle meatus, nasopharynx, maxillary sinus, frontal sinus, and sphenoid sinus for investigation using broad-range bacterial 16S ribosomal RNA (rRNA) sequencing. RESULTS: Between-subject variability in bacterial microbiota was substantially greater than within-subject variability. The middle meatus was fairly representative of the underlying sinuses, although corynebacteria were detected at higher abundances in the middle meatus, relative to the maxillary (p < 0.1), frontal (p < 0.05), or sphenoid (p < 0.1) sinuses. CONCLUSION: Interpersonal variation of the upper airway microbiome greatly outweighs niche-specific differences. The middle meatus is a fair representation of the underlying sinuses and may be considered for use as a simple single site for sampling in longitudinal studies or in subjects who have not undergone sinus surgery.
Assuntos
Microbiota , Seios Paranasais/microbiologia , Rinite/microbiologia , Sinusite/microbiologia , Adulto , Idoso , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Bacteriano/genética , RNA Ribossômico 16S/genéticaRESUMO
BACKGROUND: Iron therapy induces inflammation, which could decrease iron absorption. Increased exposure of iron in the gut could also alter microbiome file. Providing antioxidants such as vitamin E with iron therapy has been associated with reduced oxidative potential. OBJECTIVE: The aim of the present study was to test the efficacy of adding vitamin E to therapeutic iron therapy on iron repletion, inflammation markers, and gut microbiome in iron-deficient infants and toddlers. DESIGN: This was a randomized, double-blind, control trial in which infants and toddlers (Denver, CO metro area) who were at risk of iron deficiency were screened. Eligible participants were randomized to receive iron therapy (6 mgâ·âkgâ·âday) plus placebo (nâ=â22) or iron (6 mgâ·âkgâ·âday) and vitamin E (18 mg/day, nâ=â14) for 8 weeks. Iron and inflammation status, and gut microbiome (16S sequencing) were analyzed in all participants before and after the treatment. RESULTS: After 8 weeks of treatment, average serum ferritin level returned to normal for both ironâ+âplacebo and ironâ+âvitamin E groups at 33.3â±â20.2 and 33.5â±â21.5 µg/L, respectively. Serum vitamin E concentration increased in ironâ+âvitamin E group. No change over time was observed regarding serum interleukin-4, tumor necrosis factor-α, or fecal calprotectin. The relative abundance of the genus Roseburia (phylum Firmicutes), a butyrate producer, increased in the Feâ+âE group (Δ1.3%, Pâ<â0.01). Also at the genus level, the genus Escherichia decreased by 1.2% on average among all participants (effect of time Pâ=â0.01). CONCLUSIONS: Using a therapeutic iron dose of 6 mgâ·âkgâ·âday is effective in treating iron deficiency during an 8-week period, without inducing persistent inflammatory response. Changes of the gut microbiome raised the possibility that antioxidant therapy in conjunction with therapeutic iron supplementation could potentially improve microbial community profiles in the intestinal tract.
Assuntos
Anemia Ferropriva/tratamento farmacológico , Antioxidantes/uso terapêutico , Microbioma Gastrointestinal , Ferro/administração & dosagem , Vitamina E/administração & dosagem , Anemia Ferropriva/microbiologia , Pré-Escolar , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Ferritinas/sangue , Humanos , Lactente , Masculino , RNA Ribossômico 16S/genética , Vitamina E/sangueRESUMO
OBJECTIVES: Bacterial colonization and succession of the human intestine shape development of immune function and risk for allergic disease, yet these processes remain poorly understood. We investigated the relations between delivery mode, initial bacterial inoculation of the infant oropharynx (OP), and intestinal colonization. METHODS: We prospectively collected maternal rectal and vaginal swabs, infant OP aspirates, and infant stool from 23 healthy mother/infant pairs delivering by cesarean (CS) or vaginal delivery (VD) in an academic hospital. Bacterial abundance (16S rRNA sequencing) and community similarity between samples were compared by delivery mode. Shotgun DNA metagenomic sequencing of infant stool was performed. RESULTS: VD infants had higher abundance of Firmicutes (mainly lactobacilli) in OP aspirates whereas CS OP aspirates were enriched in skin bacteria. OP aspirates were more similar to maternal vaginal and rectal microbiomes in VD compared with CS. Bacteroidetes were more abundant through 6 weeks in stool of VD infants. Infant fecal microbiomes in both delivery groups did not resemble maternal rectal or vaginal microbiomes. Differences in fecal bacterial gene potential between CS and VD at 6 weeks clustered in metabolic pathways and were mediated by abundance of Proteobacteria and Bacteroidetes. CONCLUSIONS: CS infants exhibited different microbiota in the oral inoculum, a chaotic pattern of bacterial succession, and a persistent deficit of intestinal Bacteroidetes. Pioneer OP bacteria transferred from maternal vaginal and intestinal communities were not prominent constituents of the early infant fecal microbiome. Oral inoculation at birth may impact the intestinal microenvironment, thereby modulating early succession of intestinal bacteria.
Assuntos
Parto Obstétrico/métodos , Fezes/microbiologia , Intestinos/microbiologia , Microbiota , Faringe/microbiologia , Adulto , Parto Obstétrico/efeitos adversos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Estudos Prospectivos , Reto/microbiologia , Análise de Sequência de DNA , Pele/microbiologia , Vagina/microbiologiaRESUMO
BACKGROUND: Saline nasal irrigation is effective in the treatment of sinonasal disorders, including chronic rhinosinusitis (CRS). Despite bacterial contamination in rinse bottles and reports of infections from contaminated irrigation water, tap water is still used by â¼50% of irrigation users, raising a potential public health concern. This study aimed to determine whether bacteria from the water supply used in sinus irrigations colonizes the paranasal sinuses. METHODS: Samples were taken from the: (1) water used for irrigation, (2) faucet or container the water originated from, (3) rinse bottle, and (4) postoperative ethmoid cavity from 13 subjects with CRS. Microbiota were characterized using quantitative polymerase chain reaction (qPCR) and 16S ribosomal RNA (rRNA) gene sequencing. The Morisita-Horn beta-diversity index (M-H) was used to assess similarity in microbiota between samples, and genomic analysis was performed to assess clonality of cultured bacteria. RESULTS: Of 13 subjects, 6 used distilled water, 6 used tap water, and 1 used well water in this institutional review board (IRB)-approved observational study. Well-water had markedly more bacteria than tap or distilled water. There was a trend toward tap having more bacteria than distilled water. The sinus samples were notably dissimilar to the bottle, faucet, and irrigant (M-H 0.15, 0.09, and 0.18, respectively). There was no difference in postoperative microbiotas between distilled and tap water users. CONCLUSION: The current study suggests that irrigation plays little role in establishing the sinus microbiome. Although rinsing with tap water may never be formally recommended, these data are useful to counsel patients who prefer to do so in non-endemic areas if the municipal water supply is appropriately treated.
Assuntos
Bactérias/isolamento & purificação , Seios Paranasais/microbiologia , Irrigação Terapêutica , Bactérias/genética , Contaminação de Equipamentos , Humanos , Microbiota/genética , RNA Bacteriano/análise , RNA Ribossômico 16S/análise , Irrigação Terapêutica/instrumentação , Microbiologia da ÁguaRESUMO
BACKGROUND: Endoscopic sinus surgery (ESS) enjoys high success rates, but repopulation with pathogenic bacteria is 1 of the hallmarks of poorer outcomes. There are many hypothesized sources of repopulating bacteria; however, this process remains largely unexplored. This study examined changes in the sinus microbiome after ESS and medical therapies to identify potential sources for postsurgical microbial repopulation. METHODS: Samples from the anterior nares, ethmoid sinus, and nasopharynx were taken at the time of surgery from 13 subjects undergoing ESS for chronic rhinosinusitis (CRS). Patients were treated postoperatively with 2 weeks of oral antibiotics and saline rinses. The ethmoid sinus was sampled at 2 and 6 weeks postoperatively; microbiota were characterized using quantitative polymerase chain reaction (qPCR) and 16S ribosomal RNA (rRNA) gene sequencing. The Morisita-Horn beta-diversity index (M-H) was used to compare similarity between samples. RESULTS: The bacterial burden of the ethmoid was higher 2 weeks postoperatively than 6 weeks postoperatively (p = 0.01). The 6-week samples most closely represented the anterior nares and ethmoid at surgery (M-H = 0.58 and 0.59, respectively), and were least similar to the nasopharynx (M-H = 0.28). Principal coordinates analysis (PCoA) plots illustrate that the ethmoid microbiota temporarily shifted after surgery and antibiotics but returned toward baseline in many subjects. CONCLUSION: Bacterial communities colonizing the ethmoid 6 weeks postoperatively were most similar to anterior nasal cavity and pretreatment sinus microbial profiles, indicating a high degree of resilience in the sinonasal microbiome of most subjects. Interestingly, surgery and postoperative antibiotic therapy does not appear to reduce bacterial burden, but rather, shifts the microbial consortia.
Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Seio Etmoidal/microbiologia , Microbiota , Nasofaringe/microbiologia , Rinite/cirurgia , Sinusite/cirurgia , Adulto , Idoso , Antibioticoprofilaxia/efeitos adversos , Doença Crônica , Estudos Transversais , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória/efeitos adversos , Assistência Perioperatória/métodos , Rinite/microbiologia , Sinusite/microbiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Resultado do TratamentoRESUMO
We tested the hypothesis that alterations in the intestinal microbiota are linked with the progression of type 1 diabetes (T1D). Herein, we present results from a study performed in subjects with islet autoimmunity living in the U.S. High-throughput sequencing of bacterial 16S rRNA genes and adjustment for sex, age, autoantibody presence, and HLA indicated that the gut microbiomes of seropositive subjects differed from those of autoantibody-free first-degree relatives (FDRs) in the abundance of four taxa. Furthermore, subjects with autoantibodies, seronegative FDRs, and new-onset patients had different levels of the Firmicutes genera Lactobacillus and Staphylococcus compared with healthy control subjects with no family history of autoimmunity. Further analysis revealed trends toward increased and reduced abundances of the Bacteroidetes genera Bacteroides and Prevotella, respectively, in seropositive subjects with multiple versus one autoantibody. Canonical discriminant analysis suggested that the gut microbiomes of autoantibody-positive individuals and seronegative FDRs clustered together but separate from those of new-onset patients and unrelated healthy control subjects. Finally, no differences in biodiversity were evident in seropositive versus seronegative FDRs. These observations suggest that altered intestinal microbiota may be associated with disease susceptibility.
Assuntos
Bactérias/classificação , Diabetes Mellitus Tipo 1/etiologia , Microbioma Gastrointestinal/fisiologia , Ilhotas Pancreáticas/imunologia , Adolescente , Adulto , Autoanticorpos/sangue , Autoimunidade , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Suscetibilidade a Doenças , Fezes/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/química , RNA Ribossômico 16S/genética , Estados Unidos , Adulto JovemRESUMO
BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disorder of the paranasal sinuses in which bacteria are implicated. Culture-based assays are commonly used in clinical and research practice; however, culture conditions may not accurately detect the full range of microorganisms present in a sample. The objective of this study was to determine the accuracy of clinical culture of CRS specimens compared with DNA-based molecular techniques. METHODS: Ethmoid samples from 54 CRS patients collected during endoscopic sinus surgery were analyzed by both clinical culture and 16S ribosomal RNA (rRNA) gene sequencing. The association between 16S relative abundance and detection by culture was determined using logistic regression. RESULTS: Each subject had an average of 3 isolates identified by bacterial culture and 21.5 ± 12.5 species identified by 16S sequencing. On average, 1.6 dominant taxa (>10% abundance) per subject were identified using molecular techniques, but only 47.7% of these taxa were identified by culture. Low abundance taxa (abundance <1%) were detected in only 4.5% of cultures. The odds that any organism would be detected by culture were 2.3 times higher with each 10% increase in relative abundance (p < 0.01). Conversely, only 29.5% of isolates identified by culture represented the dominant species, whereas 40% accounted for species with 1% to 10% abundance. Interestingly, 12% of isolates detected by culture were not identified by 16S pyrosequencing. CONCLUSION: Standard clinical culture is a poor representation of resident microbiota. The incorporation of modern culture-independent techniques into clinical and research practices provides additional information that may be relevant for CRS.