BACKGROUND Several studies have employed animal models to explore the association between microbiota and interleukin(IL) 10 signaling;however,limited information is available about the human microbiome.AIM To characte...BACKGROUND Several studies have employed animal models to explore the association between microbiota and interleukin(IL) 10 signaling;however,limited information is available about the human microbiome.AIM To characterize the microbiome in patients with IL10 RA mutations and to explore the association between gut dysbiosis and disease severity.METHODS Fecal samples were collected from patients who were diagnosed with loss-offunction mutations in the IL10 RA gene between January 2017 and July 2018 at the Children’s Hospital of Fudan University.Age-matched volunteer children were recruited as healthy controls.Patients with Crohn’s disease(CD) were used as disease controls to standardize the antibiotic exposure.Microbial DNA was extracted from the fecal samples.All analyses were based on the 16 S rRNA gene sequencing data.RESULTS Seventeen patients with IL10 RA mutations(IL10 RA group),17 patients with pediatric CD, and 26 healthy children were included.Both patients with IL10 RA mutations and those with CD exhibited a reduced diversity of gut microbiome with increased variability.The relative abundance of Firmicutes was substantially increased in the IL10 RA group(P=0.02).On further comparison of the relative abundance of taxa between patients with IL10 RA mutations and healthy children,13 taxa showed significant differences.The IL10 RA-specific dysbiosis indices exhibited a significant positive correlation with weighted pediatric CD activity index and simple endoscopic score for CD.CONCLUSION In patients with IL10 RA mutations and early onset inflammatory bowel disease,gut dysbiosis shows a moderate association with disease severity.展开更多
BACKGROUND Infantile-onset inflammatory bowel disease(IO-IBD)occurs in very young children and causes severe clinical manifestations,which has poor responses to traditional inflammatory bowel disease(IBD)treatments.At...BACKGROUND Infantile-onset inflammatory bowel disease(IO-IBD)occurs in very young children and causes severe clinical manifestations,which has poor responses to traditional inflammatory bowel disease(IBD)treatments.At present,there are no simple and reliable laboratory indicators for early screening IO-IBD patients,especially those in whom the disease is caused by monogenic diseases.AIM To search for valuable indicators for early identifying IO-IBD patients,especially those in whom the disease is caused by monogenic diseases.METHODS A retrospective analysis was performed in 73 patients with IO-IBD admitted to our hospital in the past 5 years.Based on the next-generation sequencing results,they were divided into a monogenic IBD group(M-IBD)and a non-monogenic IBD group(NM-IBD).Forty age-matched patients with allergic proctocolitis(AP)were included in a control group.The clinical manifestations and the inflammatory factors in peripheral blood were evaluated.Logistic regression analysis and receiver operating characteristic(ROC)curve analysis were used to identify the screening factors and cut-off values of IO-IBD as well as monogenic IO-IBD,respectively.RESULTS Among the 44 M-IBD patients,35 carried IL-10RA mutations,and the most common mutations were c.301C>T(p.R101W,30/70)and the c.537G>A(p.T179T,17/70).Patients with higher serum tumor necrosis factor(TNF)-αvalue were more likely to have IBD[odds ratio(OR)=1.25,95%confidence interval(CI):1.05-1.50,P=0.013],while higher serum albumin level was associated with lower risk of IBD(OR=0.86,95%CI:0.74-1.00,P=0.048).The cut-off values of TNF-αand albumin were 17.40 pg/mL(sensitivity:0.78;specificity:0.88)and 36.50 g/L(sensitivity:0.80;specificity:0.90),respectively.The increased ferritin level was indicative of a genetic mutation in IO-IBD patients.Its cut-off value was 28.20 ng/mL(sensitivity:0.93;specificity:0.92).When interleukin(IL)-10 level was higher than 33.05 pg/mL(sensitivity:1.00;specificity:0.84),or the onset age was earlier than 0.21 mo(sensitivity:0.82;specificity:0.94),the presence of diseasecausing mutations in IL-10RA in IO-IBD patients was strongly suggested.CONCLUSION Serum TNF-αand albumin level could differentiate IO-IBD patients from allergic proctocolitis patients,and serum ferritin and IL-10 levels are useful indicators for early diagnosing monogenic IO-IBD.展开更多
基金Supported by the Jiujiu Charitable Trust-PIBD China.
文摘BACKGROUND Several studies have employed animal models to explore the association between microbiota and interleukin(IL) 10 signaling;however,limited information is available about the human microbiome.AIM To characterize the microbiome in patients with IL10 RA mutations and to explore the association between gut dysbiosis and disease severity.METHODS Fecal samples were collected from patients who were diagnosed with loss-offunction mutations in the IL10 RA gene between January 2017 and July 2018 at the Children’s Hospital of Fudan University.Age-matched volunteer children were recruited as healthy controls.Patients with Crohn’s disease(CD) were used as disease controls to standardize the antibiotic exposure.Microbial DNA was extracted from the fecal samples.All analyses were based on the 16 S rRNA gene sequencing data.RESULTS Seventeen patients with IL10 RA mutations(IL10 RA group),17 patients with pediatric CD, and 26 healthy children were included.Both patients with IL10 RA mutations and those with CD exhibited a reduced diversity of gut microbiome with increased variability.The relative abundance of Firmicutes was substantially increased in the IL10 RA group(P=0.02).On further comparison of the relative abundance of taxa between patients with IL10 RA mutations and healthy children,13 taxa showed significant differences.The IL10 RA-specific dysbiosis indices exhibited a significant positive correlation with weighted pediatric CD activity index and simple endoscopic score for CD.CONCLUSION In patients with IL10 RA mutations and early onset inflammatory bowel disease,gut dysbiosis shows a moderate association with disease severity.
基金Supported by Scientific Research Fund of Shanghai Municipal Health Commission,No.201640368National Natural Science Foundation of China,No.81741103The Shanghai Plan for Women and Children's Health Service Capacity Construction(Enhancing the Service Capacity of Shanghai Women and Children Health Care Institutions).
文摘BACKGROUND Infantile-onset inflammatory bowel disease(IO-IBD)occurs in very young children and causes severe clinical manifestations,which has poor responses to traditional inflammatory bowel disease(IBD)treatments.At present,there are no simple and reliable laboratory indicators for early screening IO-IBD patients,especially those in whom the disease is caused by monogenic diseases.AIM To search for valuable indicators for early identifying IO-IBD patients,especially those in whom the disease is caused by monogenic diseases.METHODS A retrospective analysis was performed in 73 patients with IO-IBD admitted to our hospital in the past 5 years.Based on the next-generation sequencing results,they were divided into a monogenic IBD group(M-IBD)and a non-monogenic IBD group(NM-IBD).Forty age-matched patients with allergic proctocolitis(AP)were included in a control group.The clinical manifestations and the inflammatory factors in peripheral blood were evaluated.Logistic regression analysis and receiver operating characteristic(ROC)curve analysis were used to identify the screening factors and cut-off values of IO-IBD as well as monogenic IO-IBD,respectively.RESULTS Among the 44 M-IBD patients,35 carried IL-10RA mutations,and the most common mutations were c.301C>T(p.R101W,30/70)and the c.537G>A(p.T179T,17/70).Patients with higher serum tumor necrosis factor(TNF)-αvalue were more likely to have IBD[odds ratio(OR)=1.25,95%confidence interval(CI):1.05-1.50,P=0.013],while higher serum albumin level was associated with lower risk of IBD(OR=0.86,95%CI:0.74-1.00,P=0.048).The cut-off values of TNF-αand albumin were 17.40 pg/mL(sensitivity:0.78;specificity:0.88)and 36.50 g/L(sensitivity:0.80;specificity:0.90),respectively.The increased ferritin level was indicative of a genetic mutation in IO-IBD patients.Its cut-off value was 28.20 ng/mL(sensitivity:0.93;specificity:0.92).When interleukin(IL)-10 level was higher than 33.05 pg/mL(sensitivity:1.00;specificity:0.84),or the onset age was earlier than 0.21 mo(sensitivity:0.82;specificity:0.94),the presence of diseasecausing mutations in IL-10RA in IO-IBD patients was strongly suggested.CONCLUSION Serum TNF-αand albumin level could differentiate IO-IBD patients from allergic proctocolitis patients,and serum ferritin and IL-10 levels are useful indicators for early diagnosing monogenic IO-IBD.
