RESUMO
Modern precision sequencing techniques have established humans as a holobiont that live in symbiosis with the microbiome. Microbes play an active role throughout the life of a human ranging from metabolism and immunity to disease tolerance. Hence, it is of utmost significance to study the eukaryotic host in conjunction with the microbial antigens to obtain a complete picture of the host-microbiome crosstalk. Previous attempts at profiling host-microbiome interactions have been either superficial or been attempted to catalogue eukaryotic transcriptomic profile and microbial communities in isolation. Additionally, the nature of such immune-microbial interactions is not random but spatially organised. Hence, for a holistic clinical understanding of the interplay between hosts and microbiota, it's imperative to concurrently analyze both microbial and host genetic information, ensuring the preservation of their spatial integrity. Capturing these interactions as a snapshot in time at their site of action has the potential to transform our understanding of how microbes impact human health. In examining early-life microbial impacts, the limited presence of communities compels analysis within reduced biomass frameworks. However, with the advent of spatial transcriptomics we can address this challenge and expand our horizons of understanding these interactions in detail. In the long run, simultaneous spatial profiling of host-microbiome dialogues can have enormous clinical implications especially in gaining mechanistic insights into the disease prognosis of localised infections and inflammation. This review addresses the lacunae in host-microbiome research and highlights the importance of profiling them together to map their interactions while preserving their spatial context.
Assuntos
Microbiota , Simbiose , Humanos , Bactérias/genética , Microbiota/genética , Interações MicrobianasRESUMO
OBJECTIVE: To determine whether proton pump inhibitor (PPI) exposure is associated with an increased risk of developing eosinophilic esophagitis (EoE) in children with esophageal atresia (EA). STUDY DESIGN: A retrospective chart review of children with EA from January 1, 2005 to December 31, 2020 was undertaken at Sydney Children's Hospital Randwick. Children with EA and EoE (cases) were matched (1:2) to children with only EA (controls) to compare PPI exposure. Other early-life factors such as infantile antibiotic exposure and personal or family history of atopy were also analyzed using simple and multivariable logistic regression. RESULTS: Of 184 children with EA, 46 (25%) developed EoE during this period. Thirty-eight EoE participants were matched to 76 controls. Children with EoE and EA received PPI for significantly higher durations (p = .018) and at significantly higher cumulative doses (p = .017) than controls. Food allergy (adjusted odds ratio [aOR], 7.317; 95% confidence interval [CI], 2.244-23.742), family history of atopy (aOR, 3.504; 95% CI, 1.268-9.682), and infantile antibiotic exposure (aOR, 1.040; 95% CI, 1.006-1.075) were also significantly associated with an increased risk of developing EoE in the EA cohort. CONCLUSIONS: Prolonged duration and high cumulative dose of PPI exposure were significantly associated with subsequent EoE development in children with EA. Food allergy, family history of atopy, and infantile antibiotic exposure in EA were also significantly associated with an increased risk of EoE development.
Assuntos
Antibacterianos , Esofagite Eosinofílica , Atresia Esofágica , Inibidores da Bomba de Prótons , Humanos , Inibidores da Bomba de Prótons/efeitos adversos , Esofagite Eosinofílica/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Atresia Esofágica/complicações , Antibacterianos/efeitos adversos , Fatores de Risco , Pré-Escolar , Criança , Estudos de Casos e Controles , LactenteRESUMO
OBJECTIVES: This study aims to compare the intestinal microbiota and intestinal inflammation of children with esophageal atresia (EA) to matched healthy controls, and to investigate the relationship between these factors and clinical outcomes. METHODS: A cross-sectional study of 35 children with EA and 35 matched healthy controls (HC) from a single tertiary pediatric hospital in Australia was conducted. Demographic and dietary data were collected using surveys. Stool samples were analyzed using 16S rRNA sequencing, and fecal calprotectin measurements were used to measure intestinal inflammation. Comparisons were made between the groups, and correlations between the microbiota and clinical factors were investigated in the EA cohort. RESULTS: Compared to HC, children with EA had similar alpha diversity, but beta diversity analysis revealed clustering of EA and HC cohorts. Children with EA had a significantly higher relative abundance of the order Lactobacillales, and a lower abundance of the genus uncultured Bacteroidales S24-7. Fecal calprotectin was significantly higher in children with EA compared to HC. In the EA cohort, children taking proton pump inhibitors (PPI's) had lower alpha diversity and higher calprotectin levels compared to those not taking PPI's. There was a negative correlation between calprotectin and length/height-for-age z scores, and children with higher calprotectin levels had a greater burden of gastrointestinal symptoms. CONCLUSIONS: Children with EA have an altered intestinal microbiota compared to HC, which is likely related to PPI use, and may be impacting on growth and quality of life. It is important to rationalize PPI use in this cohort.
Assuntos
Atresia Esofágica , Humanos , Criança , Atresia Esofágica/complicações , Atresia Esofágica/cirurgia , Disbiose , RNA Ribossômico 16S , Estudos Transversais , Qualidade de Vida , Inflamação , Complexo Antígeno L1 Leucocitário/análise , Fezes/químicaRESUMO
OBJECTIVES: Children with esophageal atresia (EA) often have feeding difficulties and dysphagia, which may compromise their nutritional status. This study aimed to compare dietary intake between children with EA and matched healthy controls (HC) and to investigate the relationship between dietary factors, growth, dysphagia, and feeding difficulties in the EA cohort. METHODS: This cross-sectional cohort study recruited children with EA and HC aged 2-17 years from a tertiary pediatric hospital in Australia. Growth parameters were measured. Dietary intake was assessed using the validated Australian Child and Adolescent Eating Survey. Dysphagia and feeding difficulties were assessed using objective questionnaires. RESULTS: Twenty-one children with EA were matched for age and sex with 21 HC. Compared to HC, children with EA had lower mean z scores for height-for-age, but mean weight-for-age and body mass index-for-age z scores were similar. Energy intake was similar between the groups. The diet of children with EA consisted of a higher proportion of fats and lower proportion of carbohydrates compared to matched HC. Dysphagia severity in children with EA positively correlated with proportion of energy from fats and saturated fats. CONCLUSIONS: Children with EA have similar energy intake and growth parameters to HC, but their diet consists of a higher proportion of fats and lower proportion of carbohydrates compared to HC. Targeted dietary interventions and parental education are necessary.
Assuntos
Transtornos de Deglutição , Atresia Esofágica , Adolescente , Austrália , Índice de Massa Corporal , Carboidratos , Criança , Estudos Transversais , Transtornos de Deglutição/etiologia , Gorduras na Dieta , Ingestão de Alimentos , Ingestão de Energia , Atresia Esofágica/complicações , Humanos , Estudos ProspectivosRESUMO
Gastroesophageal reflux is a common gastrointestinal issue that can lead to aspiration and contribute to respiratory problems. Little is known about how reflux can alter the respiratory microenvironment. We aimed to determine if the presence of gastric pepsinogen in the trachea was associated with changes in the microbial and inflammatory microenvironment. A pediatric cohort at high risk of reflux aspiration was prospectively recruited, and the tracheal microenvironment was examined. Pepsinogen A3 (PGA3) and cytokines were measured. The microbiome (bacterial and fungal) was profiled using 16S rRNA and internal transcribed spacer 2 (ITS2) amplicon sequencing. Increased bacterial richness and an altered composition driven by an enrichment of Prevotella correlated with high PGA3 levels. Fungal richness increased with PGA3, with higher Candida relative abundances observed in a subset of samples with high PGA3 levels. Source tracking of tracheal microbial taxa against taxa from matched oral and gastric samples revealed a significantly greater contribution of oral than of gastric taxa with higher PGA3 levels. Tracheal cytokines were differentially produced when stratified according to PGA3, with higher levels of interleukin-1 (IL-1)-related cytokines and IL-8 being associated with high PGA3 levels. Network analysis across cytokine and microbiome measures identified relationships between IL-1-related proteins and microbial taxa, with the presence of respiratory issues associated with higher levels of IL-1ß, IP-10, and Prevotella In conclusion, PGA3 levels in the trachea are correlated with increases in specific microbial taxa and inflammatory molecules, with an increase in oral microbes with increasing PGA3.
Assuntos
Citocinas/metabolismo , Refluxo Gastroesofágico/metabolismo , Microbioma Gastrointestinal/genética , Pepsinogênio A/metabolismo , Aspiração Respiratória/metabolismo , Traqueia/metabolismo , Adolescente , Candida/isolamento & purificação , Quimiocina CXCL10/metabolismo , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Refluxo Gastroesofágico/enzimologia , Refluxo Gastroesofágico/microbiologia , Humanos , Lactente , Inflamação/metabolismo , Inflamação/microbiologia , Interleucina-1/metabolismo , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , Masculino , Prevotella/isolamento & purificação , RNA Ribossômico 16S/genética , Aspiração Respiratória/microbiologia , Traqueia/enzimologia , Traqueia/microbiologiaRESUMO
BACKGROUND: Noninvasive and accurate methods to monitor inflammatory bowel disease are required. As a planned ancillary study of the prospective ImageKids cohort, we aimed to assess the performance of fecal calprotectin (FC) with comparison to 3 fecal inflammatory markers; S100A12 (FA12), tumor pyruvate kinase isoenzyme type M2 (FM2PK) and fecal osteoprotegerin (FOPG) as indicators of a number of disease characteristics. METHODS: The ImageKids study was a multicenter study designed to develop 2 magnetic resonance enterography-based measures for children with Crohn disease (6-18 years old). All patients underwent magnetic resonance enterography, a complete ileocolonoscopic evaluation and provided a fecal sample. Fecal samples were assay for FC, FA12, FM2PK, and FOPG by ELISA. RESULTS: One-hundred fifty-six children provided 190 fecal samples. Median (interquartile range) for fecal makers were FC, 602 (181-1185) µg/g; FA12, 21 (3-109) µg/g; FM2PK, 16 (2-20) U/mL; and FOPG, 125 (125-312) µg/g. All markers correlated with simple endoscopic severity index for Crohn disease and with other constructs of disease activity, but FC had the highest overall correlations. FA12, however, predicted mucosal healing with significantly higher specificity (87% vs 70%, Pâ=â0.004) and equivalent sensitivity (91% vs 90%) compared to FC. CONCLUSION: This study has confirmed that FC is useful, and overall best, marker to monitor mucosal inflammation in inflammatory bowel disease. FA12, however, appears to be a more suitable maker for prediction of mucosal healing in children.
Assuntos
Doença de Crohn , Adolescente , Biomarcadores/análise , Criança , Colonoscopia , Doença de Crohn/diagnóstico , Fezes/química , Humanos , Inflamação , Complexo Antígeno L1 Leucocitário , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND & AIMS: Bowel healing is an important goal of therapy for patients with Crohn's disease (CD). Although there have been many studies of mucosal healing, transmural healing (ie, in the bowel wall) has not been investigated in children. We analyzed data from the ImageKids study to determine associations among mucosal, transmural healing and levels of calprotectin and C-reactive protein in children with CD. METHODS: We collected data from a multi-center study designed to develop 2 magnetic resonance enterography (MRE)-based measures for children with CD (6-18 years old). In our analysis of 151 children (mean age, 14.2 ± 2.4 years), all patients underwent MRE and a complete ileocolonoscopic evaluation; fecal levels of calprotectin and blood levels of C-reactive protein were measured. Mucosal healing was defined as simple endoscopic severity index in CD score below 3, transmural healing as an MRE visual analogue score below 20 mm, and deep healing as a combination of transmural and mucosal healing. RESULTS: We identified mucosal healing with transmural inflammation in 9 children (6%), transmural healing with mucosal inflammation in 38 children (25%), deep healing in 21 children (14%), and mucosal and transmural inflammation in 83 children (55%). The median level of calprotectin was lowest in children with deep healing (mean level, 10 µg/g; interquartile range, 10-190 µg/g), followed by children with either transmural or mucosal inflammation, and highest in children with mucosal and transmural inflammation (810 µg/g; interquartile range, 539-1737 µg/g) (P < .001). Fecal level of calprotectin identified children with deep healing with an area under the receiver operating characteristic curve value of 0.93 (95% CI, 0.89-0.98); level of C-reactive protein identified children with deep healing with an area under the receiver operating characteristic curve value of 0.81 (95% CI, 0.71-0.9). A calprotectin cutoff value of 100 µg/g identified children with deep healing with 71% sensitivity and 92% specificity; a cutoff value of 300 µg/g identified children with mucosal healing with 80% sensitivity and 81% specificity. CONCLUSIONS: In a prospective study of children with CD, we found that one-third have healing in only the mucosa or the bowel wall (not both). Levels of fecal calprotectin below 300 µg/identify children with mucosal healing, but a lower cutoff value (below 100 µg/g) is needed to identify children with deep healing. Clinicaltrials.gov no: NCT01881490.
Assuntos
Doença de Crohn/diagnóstico , Doença de Crohn/patologia , Monitoramento de Medicamentos/métodos , Fezes/química , Intestinos/patologia , Complexo Antígeno L1 Leucocitário/análise , Adolescente , Análise Química do Sangue , Proteína C-Reativa/análise , Criança , Endoscopia Gastrointestinal , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND AND AIMS: Capsule endoscopy (CE) is the most sensitive test to diagnose small-bowel Crohn's disease (CD). Conventional parameters poorly assess CD remission, and although fecal biomarkers assess colonic activity, their role in assessing remission is uncertain. We report CE findings in small-bowel CD patients in clinical remission compared with fecal biomarkers and standard clinical tools to determine mucosal remission and predict relapses. METHODS: Forty-three adult small-bowel CD patients in clinical remission (Crohn's Disease Activity Index [CDAI] <150) were prospectively enrolled at 4 academic centers and followed clinically for 12 months. Baseline CE studies were scored using the Capsule Endoscopy Scoring Index (CESI or Lewis score). Baseline and endpoint fecal biomarkers were assayed. RESULTS: CE findings were normal in 17 patients (40%), mild inflammation in 19 (44%), and moderate to severe inflammation in 7 (16%). Of the 26 patients (60%) with mucosal inflammation on CE, 85% had elevated baseline fecal calprotectin and 77% elevated lactoferrin level. Calprotectin and lactoferrin were normal in all patients without inflammation and elevated in all with moderate to severe inflammation. CESI correlated significantly with calprotectin, lactoferrin, and S100A12 levels but not either CDAI or C-reactive protein. During follow-up, 14% of patients exhibited a clinical flare; all had mucosal inflammation at CE and 83% had elevated baseline calprotectin and lactoferrin levels. CONCLUSIONS: In small-bowel CD patients in clinical remission, many had ongoing mucosal inflammation assessed by CE and fecal biomarkers. Only some developed a clinical flare during medium-term follow-up. These findings suggest CE and fecal biomarkers are useful in monitoring small-bowel CD progress.
Assuntos
Endoscopia por Cápsula , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/metabolismo , Fezes/química , Lactoferrina/análise , Complexo Antígeno L1 Leucocitário/análise , Adulto , Idoso , Biomarcadores/análise , Proteína C-Reativa/metabolismo , Doença de Crohn/tratamento farmacológico , Feminino , Humanos , Intestino Delgado , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Indução de Remissão , Proteína S100A12/análise , Índice de Gravidade de Doença , Exacerbação dos SintomasRESUMO
Over the last two decades, knowledge on fecal biomarkers has substantially increased. Nowadays, these non-invasive markers of inflammation have significant clinical utility in the management of inflammatory bowel disease. Their use informs the decision to perform endoscopy before diagnosis is made right through to influencing therapeutic choices and the need for interval endoscopic assessment. In this review, the roles of two S100 proteins, calprotectin, and S100A12 are described along with that of lactoferrin, in the context of inflammatory bowel disease.
Assuntos
Fezes/química , Doenças Inflamatórias Intestinais/diagnóstico , Complexo Antígeno L1 Leucocitário/análise , Proteínas S100/análise , Proteína S100A12/análise , Biomarcadores/análise , HumanosRESUMO
There is increasing importance placed upon noninvasive assessment of gut inflammation. These tools are likely to be the key in differentiating intestinal inflammatory disease from functional disorders and in monitoring the response to intervention in individuals with known inflammatory conditions. Although various noninvasive markers are currently available, they have limitations and do not provide ideal utility. This review focuses on emerging markers of gut inflammation, highlighting the potential of specific markers.
Assuntos
Biomarcadores/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Animais , Humanos , Inflamação/metabolismoRESUMO
AIMS: Disease-specific knowledge may influence disease outcome and quality of life in children with inflammatory bowel disease (IBD). This prospective study aimed to define IBD-related knowledge in a group of Australian children with IBD and their parents using a validated measure of disease-specific knowledge, the Inflammatory Bowel Disease Knowledge Inventory Device (IBD-KID). METHODS: Children (less than 18 years) diagnosed with IBD who were members of the Australian patient support organisation were identified. Each family was sent copies of the IBD-KID. Children aged 10-18 years and all parents were asked to complete the IBD-KID and to also provide demographic details and disease characteristics. RESULTS: Replies were received from 196 families: 262 parents and 128 children completed questionnaires. Most children had a diagnosis of Crohn disease (65%) and 51% were male. Children diagnosed in the preceding 6 years scored higher than those with longer time since diagnosis. Parents had better scores in the IBD-KID than the children (P < 0.0001). Overall, parents and children had poor understanding of key management issues for IBD (such as side effects of steroids), important outcomes (e.g. growth) and the use of complementary therapies. CONCLUSIONS: Consistent patterns of IBD-related knowledge were noted in this large group of Australian children with IBD and their parents. Measurement of disease-related knowledge with the IBD-KID can identify gaps in understanding, thereby permitting focused educational activities. Although these knowledge gaps may impact upon outcomes, further prospective studies are now required to elucidate the relationships between enhanced knowledge and specific outcomes.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Doenças Inflamatórias Intestinais , Adolescente , Austrália , Criança , Feminino , Humanos , Masculino , Pais , Inquéritos e QuestionáriosRESUMO
Campylobacter concisus is a member of the oral microbiota that has been associated with the development of inflammatory bowel diseases. However, the role of the bacterium in disease aetiology remains poorly understood. Here, we examine optimal conditions for the growth of C. concisus, and the pathogenic potential of this bacterium in human gastrointestinal cells from the upper tract. Further, the presence of C. concisus in the lower tract of Crohn's disease (CD) patients undergoing therapy is observed, and the associations of C. concisus with the abundance of other microbial taxa and compounds they produce are evaluated. C. concisus strains had the ability to tolerate moderate levels of acidity, adhere to and invade esophageal and gastric cells; however, these properties did not correlate with their pathogenic potential in intestinal cells. The presence of the bacterium in the lower gut of CD patients was associated with an increased relative abundance of Faecalibacterium and Lachnospiraceae incertae sedis. Short chain fatty acids that can be produced by these microbial species did not appear to be responsible for this association. However, we identified genetic similarity between C. concisus and Firmicutes, specifically within aspartate and glutamate racemases. The potential pathogenesis of C. concisus in the upper gastrointestinal tract, and the responsiveness of the bacterium to therapy in a subset of CD patients warrant further investigation into whether this bacterium has a causal role in disease or its presence is incidental.
Assuntos
Sangue/microbiologia , Campylobacter/classificação , Campylobacter/patogenicidade , Doença de Crohn/microbiologia , Ácidos Graxos Voláteis/metabolismo , Firmicutes/classificação , Trato Gastrointestinal/microbiologia , Aderência Bacteriana/fisiologia , Campylobacter/genética , Campylobacter/metabolismo , Infecções por Campylobacter/microbiologia , Células Cultivadas , Clostridiales/isolamento & purificação , Faecalibacterium/isolamento & purificação , Firmicutes/genética , Trato Gastrointestinal/citologia , HumanosRESUMO
BACKGROUND AND AIM: Adult patients with cystic fibrosis (CF) have an increased risk of gastrointestinal malignancies. We hypothesized that increased intestinal cell turnover beginning in childhood may explain the increased risk of malignancy in early adulthood. Therefore, we aimed to measure fecal M2-pyruvate kinase (M2-PK), a biomarker of intestinal cell turnover, in children with CF. To assess whether the increased cell turnover is secondary to intestinal inflammation, the secondary aims were to measure fecal calprotectin and evaluate its association with fecal M2-PK. METHODS: Fecal samples, for M2-PK and calprotectin measurements, were prospectively collected from children with CF and healthy controls (HC). RESULTS: Thirty-three children with CF (mean [standard deviation] 7.3 [3.8] years old; 29 pancreatic insufficient [PI]) were enrolled and compared with 33 age-matched HC. Fecal M2-PK in CF patients (median [interquartile range, IQR]: 4.7 [1.5-9.7]) was greater than HC (1.0 [1.0-1.0] U/mL; P < 0.0001), and higher in PI (median [IQR]: 5.1 [1.8-13.7]) than pancreatic sufficient patients (1.0 [1.0-1.0] U/mL; P = 0.002). Fecal calprotectin was significantly elevated in CF than HC (median [IQR] 61.3 [43.8-143.8] vs 19.5 [19.5-35.1] mg/kg; P < 0.0001). However, there was no correlation between fecal M2-PK and fecal calprotectin levels among subjects with CF (r = 0.29; P = 0.1). CONCLUSION: Increased intestinal cell turnover is present in children with PI CF. The lack of relationship between fecal M2-PK and calprotectin suggests that contributing factor(s) other than inflammation may be present.
Assuntos
Fibrose Cística/patologia , Fezes/enzimologia , Enteropatias/diagnóstico , Piruvato Quinase/análise , Adolescente , Biomarcadores/análise , Criança , Pré-Escolar , Neoplasias do Colo/etiologia , Fibrose Cística/complicações , Fezes/química , Feminino , Humanos , Lactente , Inflamação , Enteropatias/complicações , Enteropatias/patologia , Intestinos/patologia , Complexo Antígeno L1 Leucocitário/análise , Masculino , Estudos Prospectivos , RiscoRESUMO
OBJECTIVES: Vitamin D deficiency is common in children with inflammatory bowel disease (IBD). The aim of this study was to determine the safety and efficacy of stoss therapy on vitamin D levels during a period of 6 months in children with IBD and vitamin D deficiency (<50 nmol/L). METHODS: A retrospective chart review was undertaken, focusing upon children managed in the IBD clinic at Sydney Children's Hospital between 2006 and 2010. Those with a 25-hydroxyvitamin D (25-OHD) level <50 nmol/L and those who received stoss therapy were included in this study. RESULTS: A total of 76 children received stoss therapy. There was a significant and sustained increase in 25-OHD levels at all of the time points compared with baseline (40.8â±â7.5 nmol/L), 1 month (145.6â±â51.8 nmol/L), 3 months (87.1â±â28.4 nmol/L), and 6 months 69.2â±â31.3 nmol/L). There were no significant changes in serum calcium, phosphate, or parathyroid hormone at any time points. CONCLUSIONS: Stoss therapy safely and effectively achieved and maintained a level of 25-OHD >50 nmol/L during 6 months in these children with IBD. Further prospective studies are now required to confirm this finding and establish whether this intervention has other benefits.
Assuntos
Calcifediol/sangue , Colecalciferol/administração & dosagem , Suplementos Nutricionais , Doenças Inflamatórias Intestinais/fisiopatologia , Deficiência de Vitamina D/dietoterapia , Adolescente , Calcifediol/metabolismo , Criança , Pré-Escolar , Colecalciferol/efeitos adversos , Colecalciferol/metabolismo , Colecalciferol/uso terapêutico , Estudos de Coortes , Colite Ulcerativa/fisiopatologia , Doença de Crohn/fisiopatologia , Suplementos Nutricionais/efeitos adversos , Feminino , Seguimentos , Hospitais Pediátricos , Humanos , Masculino , Prontuários Médicos , New South Wales , Ambulatório Hospitalar , Estudos Retrospectivos , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/etiologia , Deficiência de Vitamina D/metabolismoRESUMO
BACKGROUND: Necrotizing enterocolitis (NEC) leads to significant morbidity and mortality in the neonatal intensive care unit. Although current evidence would suggest that bacteria contribute to the pathogenesis of NEC, no single bacterium has yet been identified. AIMS: The aims of this study were to investigate fecal S100A12 concentrations and the intestinal bacterial community in premature infants (24-32 weeks) and investigate any associations between the microbiota and the development of NEC. METHODS: Meconium and feces were collected from premature newborn infants (between 24 and 32 weeks gestation) over the first 4 weeks of life. Fecal S100A12 concentrations were assayed by immunoassay, and samples were subject to 16S rDNA analysis using next-generation sequencing techniques. RESULTS: Fecal samples were collected from four infants that developed NEC and 18 control infants. Prior to developing NEC, fecal S100A12 concentrations were not elevated; however, following NEC diagnosis, concentrations were highly elevated. The fecal bacterial communities of infants with NEC did not differ significantly from control infants. However, potentially pathogenic bacteria were detected in significantly more infants with NEC than in controls (p = 0.0007). CONCLUSION: At birth, fecal S100A12 concentrations were not elevated in premature infants subsequently developing NEC in this cohort. Following NEC diagnosis, S100A12 concentrations were highly elevated, suggesting that this potentially could act as a marker of disease progression. Higher detection rates of potentially pathogenic bacteria in NEC infants suggest that a range of potentially pathogenic bacteria may collectively contribute to NEC pathogenesis.
Assuntos
Bactérias/classificação , Enterocolite Necrosante/microbiologia , Enterocolite Necrosante/patologia , Inflamação/metabolismo , Infecções Oportunistas/microbiologia , Bactérias/isolamento & purificação , Estudos de Casos e Controles , Fezes/química , Fezes/microbiologia , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Mecônio/química , Mecônio/microbiologia , Proteína S100A12/análise , Proteína S100A12/genética , Proteína S100A12/metabolismoRESUMO
BACKGROUND: Defects in bacterial host defenses in the cystic fibrosis (CF) airways have been extensively investigated, but the role of the intestinal innate immune system in CF is unknown. Human ß-defensin 2 (HBD-2) is an antimicrobial protein produced by epithelial surfaces and upregulated by inflammation. Its expression in the CF intestine is unknown. AIM: To determine whether HBD-2 was present in the feces of patients with CF, and to compare fecal HBD-2 levels between CF and healthy controls (HC). To compare fecal HBD-2 levels in inflamed and noninflamed states, as measured by fecal calprotectin, as a secondary aim. METHODS: Feces from children with CF and HC were collected for analysis. RESULTS: Thirty-three CF patients and 33 HC were recruited. All CF patients had detectable fecal HBD-2. There was no difference between fecal HBD-2 in CF and HC (median (IQR) 49.1 (19.7-77.2) versus 43.4 (26.5-71.9) ng/g; P = 0.7). Fecal calprotectin was significantly higher in the CF cohort than in HC (median (IQR) 61.3 (43.8-143.8) versus 19.5 (19.5-35.1) mg/kg; P < 0.0001). There was no difference in fecal HBD-2 levels between CF subjects with fecal calprotectin ≥50 mg/kg and <50 mg/kg (50.5 (19.6-80.2) versus 43.0 (19.0-70.4); P = 0.7). There was no correlation between fecal HBD-2 and calprotectin in CF (r = 0.14; P = 0.4). CONCLUSION: Fecal HBD-2 levels were not increased in children with CF, in inflamed or noninflamed states. The lack of HBD-2 induction and upregulation under inflammatory conditions may suggest a diminished intestinal innate immune response in CF.
Assuntos
Fibrose Cística/imunologia , Enterite/imunologia , Fezes/química , Complexo Antígeno L1 Leucocitário/metabolismo , beta-Defensinas/metabolismo , Adolescente , Biomarcadores/análise , Criança , Pré-Escolar , Estudos de Coortes , Fibrose Cística/fisiopatologia , Enterite/fisiopatologia , Feminino , Hospitais Pediátricos , Humanos , Imunidade Inata , Complexo Antígeno L1 Leucocitário/imunologia , Masculino , Prognóstico , Estudos Prospectivos , Valores de Referência , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Estatísticas não Paramétricas , beta-Defensinas/imunologiaRESUMO
The objective of this Special Issue entitled 'Role of Probiotics and Prebiotics in Gut Symbiosis' is to publish reviews, clinical trials and experimental studies that focus on probiotics and prebiotics that have a role in influencing disease and promoting gastrointestinal and overall health [...].
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Prebióticos , Probióticos , Simbiose , EditoraçãoRESUMO
BACKGROUND: Emulsifiers are implicated in the pathogenesis of inflammatory bowel disease (IBD). Few studies have examined emulsifier intake in people with existing IBD. We aimed to describe the frequency of exposure to 6 selected emulsifiers in a contemporary cohort of people with IBD and compare intake with healthy controls (HCs). METHODS: Baseline food records from participants in an Australian prospective cohort study examining the microbiome of IBD patients and HCs were analyzed. Exposure to inflammatory emulsifiers polysorbate-80 (P80); carboxymethylcellulose (CMC); carrageenan; xanthan gum (XG); lecithin (soy and sunflower) and mono- and diglycerides of fatty acids (MDGs) were determined by examining ingredient lists. Frequency of emulsifier exposure between groups (IBD vs HC, Crohn's disease [CD] vs ulcerative colitis [UC], IBD children vs adults, active disease vs remission) was examined after controlling for confounders. RESULTS: Records from 367 participants were analyzed (nâ =â 176 IBD, of which there were 101 CD, 75 UC, and 191 HC patients). In total, 5022 unique food items were examined, with 18% containing 1 or more emulsifier of interest. Inflammatory bowel disease participants had significantly higher total daily emulsifier exposure compared with HCs (2.7â ±â 1.8 vs 2.3â ±â 1.6, Pâ =â .02). In IBD participants, emulsifiers with the highest daily exposure were MDGs (1.2â ±â 0.93), lecithin (0.85â ±â 0.93), and XG (0.38â ±â 0.42). There were no recorded exposures to P80. CONCLUSIONS: Inflammatory bowel disease participants were exposed to more emulsifiers than HCs. Intake of inflammatory emulsifiers were low or nonexistent, suggesting their presence in the food supply are not as common as frequently stated.
Assuntos
Emulsificantes , Doenças Inflamatórias Intestinais , Polissorbatos , Humanos , Masculino , Feminino , Adulto , Emulsificantes/efeitos adversos , Estudos Prospectivos , Estudos de Casos e Controles , Pessoa de Meia-Idade , Austrália/epidemiologia , Polissorbatos/efeitos adversos , Criança , Colite Ulcerativa , Adolescente , Adulto Jovem , Doença de Crohn , Lecitinas , Polissacarídeos Bacterianos , Carboximetilcelulose Sódica/efeitos adversos , Idoso , Exposição Dietética/efeitos adversosRESUMO
BACKGROUND: Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor (TNF) receptor super-family, is a key factor inhibiting the differentiation and activation of osteoclasts. It has recently been implicated as a disease marker for inflammatory bowel disease (IBD) yet its role in the intestinal epithelial inflammatory response remains unknown. AIM: The primary objective of this study was to investigate whether OPG has a role in intestinal inflammation and a potential role in IBD pathogenesis. METHODS: Caco-2 and HT-29 cells were grown in vitro to confluence on culture-permeable supports and then co-cultured with either TNF-α or OPG. After exposure to either TNF-α or OPG, interleukin (IL)-8 protein and mRNA levels were evaluated. Ussing chamber, western blotting, real-time polymerase chain reaction, and immunofluorescence were used to further investigate the effect of OPG on intestinal barrier integrity and function. RESULTS: Similar to TNF-α, treatment of monolayers with OPG caused increased monolayer permeability and diminished tight junction function and integrity, with loss of tight junction proteins from cell membranes. This was accompanied by elevated IL-8 protein and gene levels (P < 0.05). Western blotting also revealed that OPG, similar to TNF-α, induced NF-κB activation, as shown by inhibition of NF-κB kinase subunit-α phosphorylation. CONCLUSIONS: These results indicate that OPG has pro-inflammatory properties because it induces gut barrier dysfunction and secretion of other pro-inflammatory cytokines. These results also provide evidence that OPG is likely to exert its pro-inflammatory effects through NF-κB activation and may potently contribute to IBD pathogenesis.