BACKGROUND Obesity is associated with a significantly increased risk for chronic diarrhea,which has been proposed as Linghu’s obesity-diarrhea syndrome(ODS);however,its molecular mechanisms are largely unknown.AIM To...BACKGROUND Obesity is associated with a significantly increased risk for chronic diarrhea,which has been proposed as Linghu’s obesity-diarrhea syndrome(ODS);however,its molecular mechanisms are largely unknown.AIM To reveal the transcriptomic changes in the jejunum involved in ODS.METHODS In a cohort of 6 ODS patients(JOD group),6 obese people without diarrhea(JO group),and 6 healthy controls(JC group),high-throughput sequencing and bioinformatics analyses were performed to identify jejunal mucosal mRNA expression alterations and dysfunctional biological processes.In another cohort of 16 ODS patients(SOD group),16 obese people without diarrhea(SO group),and 16 healthy controls(SC group),serum diamine oxidase(DAO)and D-lactate(DLA)concentrations were detected to assess changes in intestinal barrier function.RESULTS The gene expression profiles of jejunal mucosa in the JO and JC groups were similar,with only 1 differentially expressed gene(DEG).The gene expression profile of the JOD group was significantly changed,with 411 DEGs compared with the JO group and 211 DEGs compared with the JC group,129 of which overlapped.The enrichment analysis of these DEGs showed that the biological processes such as digestion,absorption,and transport of nutrients(especially lipids)tended to be up-regulated in the JOD group,while the biological processes such as rRNA processing,mitochondrial translation,antimicrobial humoral response,DNA replication,and DNA repair tended to be down-regulated in the JOD group.Eight DEGs(CDT1,NHP2,EXOSC5,EPN3,NME1,REG3A,PLA2G2A,and PRSS2)may play a key regulatory role in the pathological process of ODS,and their expression levels were significantly decreased in ODS patients(P<0.001).In the second cohort,compared with healthy controls,the levels of serum intestinal barrier function markers(DAO and D-LA)were significantly increased in all obese individuals(P<0.01),but were higher in the SOD group than in the SO group(P<0.001).CONCLUSION Compared with healthy controls and obese individuals without diarrhea,patients with Linghu’s ODS had extensive transcriptomic changes in the jejunal mucosa,likely affecting intestinal barrier function and thus contributing to the obesity and chronic diarrhea phenotypes.展开更多
MéNéTRIER＇S disease （MD） is a rare diseasecharacterized by hypertrophy of gastricfolds, and nausea, emesis, abdominal painand peripheral oedema are the mainmanifestations. Hypochlorhydria and hypoalbumine...MéNéTRIER＇S disease （MD） is a rare diseasecharacterized by hypertrophy of gastricfolds, and nausea, emesis, abdominal painand peripheral oedema are the mainmanifestations. Hypochlorhydria and hypoalbuminemiaare also common.1 MD is always misdiagnosed due to itsrarity. Especially, the symptoms caused by hypoalbuminemia,for example, pleural effusions or ascites,make the correct diagnosis more difficult.展开更多
文摘BACKGROUND Obesity is associated with a significantly increased risk for chronic diarrhea,which has been proposed as Linghu’s obesity-diarrhea syndrome(ODS);however,its molecular mechanisms are largely unknown.AIM To reveal the transcriptomic changes in the jejunum involved in ODS.METHODS In a cohort of 6 ODS patients(JOD group),6 obese people without diarrhea(JO group),and 6 healthy controls(JC group),high-throughput sequencing and bioinformatics analyses were performed to identify jejunal mucosal mRNA expression alterations and dysfunctional biological processes.In another cohort of 16 ODS patients(SOD group),16 obese people without diarrhea(SO group),and 16 healthy controls(SC group),serum diamine oxidase(DAO)and D-lactate(DLA)concentrations were detected to assess changes in intestinal barrier function.RESULTS The gene expression profiles of jejunal mucosa in the JO and JC groups were similar,with only 1 differentially expressed gene(DEG).The gene expression profile of the JOD group was significantly changed,with 411 DEGs compared with the JO group and 211 DEGs compared with the JC group,129 of which overlapped.The enrichment analysis of these DEGs showed that the biological processes such as digestion,absorption,and transport of nutrients(especially lipids)tended to be up-regulated in the JOD group,while the biological processes such as rRNA processing,mitochondrial translation,antimicrobial humoral response,DNA replication,and DNA repair tended to be down-regulated in the JOD group.Eight DEGs(CDT1,NHP2,EXOSC5,EPN3,NME1,REG3A,PLA2G2A,and PRSS2)may play a key regulatory role in the pathological process of ODS,and their expression levels were significantly decreased in ODS patients(P<0.001).In the second cohort,compared with healthy controls,the levels of serum intestinal barrier function markers(DAO and D-LA)were significantly increased in all obese individuals(P<0.01),but were higher in the SOD group than in the SO group(P<0.001).CONCLUSION Compared with healthy controls and obese individuals without diarrhea,patients with Linghu’s ODS had extensive transcriptomic changes in the jejunal mucosa,likely affecting intestinal barrier function and thus contributing to the obesity and chronic diarrhea phenotypes.
文摘MéNéTRIER＇S disease （MD） is a rare diseasecharacterized by hypertrophy of gastricfolds, and nausea, emesis, abdominal painand peripheral oedema are the mainmanifestations. Hypochlorhydria and hypoalbuminemiaare also common.1 MD is always misdiagnosed due to itsrarity. Especially, the symptoms caused by hypoalbuminemia,for example, pleural effusions or ascites,make the correct diagnosis more difficult.
