Modulation of faecal metagenome in Crohn’s disease: Role of microRNAs as biomarkers

The gut microbiota plays a key role in the maintenance of intestinal homeostasis and the development and activation of the host immune system. It has been shown that commensal bacterial species can regulate the expression of host genes. 16S rRNA gene sequencing has shown that the microbiota in infla...

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Published inWorld journal of gastroenterology : WJG Vol. 24; no. 46; pp. 5223 - 5233
Main Authors Rojas-Feria, María, Romero-García, Teresa, Fernández Caballero-Rico, Jose Ángel, Pastor Ramírez, Helena, Avilés-Recio, Marta, Castro-Fernandez, Manuel, Chueca Porcuna, Natalia, Romero-Gόmez, Manuel, García, Federico, Grande, Lourdes, Del Campo, José A
Format Journal Article
LanguageEnglish
Published United States Baishideng Publishing Group Inc 14.12.2018
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Online AccessGet full text
ISSN1007-9327
2219-2840
2219-2840
DOI10.3748/wjg.v24.i46.5223

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Abstract The gut microbiota plays a key role in the maintenance of intestinal homeostasis and the development and activation of the host immune system. It has been shown that commensal bacterial species can regulate the expression of host genes. 16S rRNA gene sequencing has shown that the microbiota in inflammatory bowel disease (IBD) is abnormal and characterized by reduced diversity. MicroRNAs (miRNAs) have been explored as biomarkers and therapeutic targets, since they are able to regulate specific genes associated with Crohn's disease (CD). In this work, we aim to investigate the composition of gut microbiota of active treatment-naïve adult CD patients, with miRNA profile from gut microbiota. To investigate the composition of gut microbiota of active treatment-naïve adult CD patients, with miRNA profile from gut microbiota. Patients attending the outpatient clinics at Valme University Hospital without relevant co-morbidities were matched according to age and gender. Faecal samples of new-onset CD patients, free of treatment, and healthy controls were collected. Faecal samples were homogenized, and DNA was amplified by PCR using primers directed to the 16S bacterial rRNA gene. Pyrosequencing was performed using GS-Junior platform. For sequence analysis, MG-RAST server with the database Ribosomal Project was used. MiRNA profile and their relative abundance were analyzed by quantitative PCR. Microbial community was characterized using 16S rRNA gene sequencing in 29 samples ( = 13 CD patients, and = 16 healthy controls). The mean Shannon diversity was higher in the healthy control population compared to CD group (5.5 3.7). A reduction in and an increase in were found. class was also significantly reduced in CD. Principal components analysis showed a grouping pattern, identified in most of the subjects in both groups, showing a marked difference between control and CD groups. A functional metabolic study showed that a lower metabolism of carbohydrates ( = 0.000) was found in CD group, while the metabolism of lipids was increased. In CD patients, three miRNAs were induced in affected mucosa: mir-144 (6.2 ± 1.3 fold), mir-519 (21.8 ± 3.1) and mir-211 (2.3 ± 0.4). Changes in microbial function in active non-treated CD subjects and three miRNAs in affected non-affected mucosa have been found. miRNAs profile may serve as a biomarker.
AbstractList The gut microbiota plays a key role in the maintenance of intestinal homeostasis and the development and activation of the host immune system. It has been shown that commensal bacterial species can regulate the expression of host genes. 16S rRNA gene sequencing has shown that the microbiota in inflammatory bowel disease (IBD) is abnormal and characterized by reduced diversity. MicroRNAs (miRNAs) have been explored as biomarkers and therapeutic targets, since they are able to regulate specific genes associated with Crohn's disease (CD). In this work, we aim to investigate the composition of gut microbiota of active treatment-naïve adult CD patients, with miRNA profile from gut microbiota. To investigate the composition of gut microbiota of active treatment-naïve adult CD patients, with miRNA profile from gut microbiota. Patients attending the outpatient clinics at Valme University Hospital without relevant co-morbidities were matched according to age and gender. Faecal samples of new-onset CD patients, free of treatment, and healthy controls were collected. Faecal samples were homogenized, and DNA was amplified by PCR using primers directed to the 16S bacterial rRNA gene. Pyrosequencing was performed using GS-Junior platform. For sequence analysis, MG-RAST server with the database Ribosomal Project was used. MiRNA profile and their relative abundance were analyzed by quantitative PCR. Microbial community was characterized using 16S rRNA gene sequencing in 29 samples ( = 13 CD patients, and = 16 healthy controls). The mean Shannon diversity was higher in the healthy control population compared to CD group (5.5 3.7). A reduction in and an increase in were found. class was also significantly reduced in CD. Principal components analysis showed a grouping pattern, identified in most of the subjects in both groups, showing a marked difference between control and CD groups. A functional metabolic study showed that a lower metabolism of carbohydrates ( = 0.000) was found in CD group, while the metabolism of lipids was increased. In CD patients, three miRNAs were induced in affected mucosa: mir-144 (6.2 ± 1.3 fold), mir-519 (21.8 ± 3.1) and mir-211 (2.3 ± 0.4). Changes in microbial function in active non-treated CD subjects and three miRNAs in affected non-affected mucosa have been found. miRNAs profile may serve as a biomarker.
The gut microbiota plays a key role in the maintenance of intestinal homeostasis and the development and activation of the host immune system. It has been shown that commensal bacterial species can regulate the expression of host genes. 16S rRNA gene sequencing has shown that the microbiota in inflammatory bowel disease (IBD) is abnormal and characterized by reduced diversity. MicroRNAs (miRNAs) have been explored as biomarkers and therapeutic targets, since they are able to regulate specific genes associated with Crohn's disease (CD). In this work, we aim to investigate the composition of gut microbiota of active treatment-naïve adult CD patients, with miRNA profile from gut microbiota.BACKGROUNDThe gut microbiota plays a key role in the maintenance of intestinal homeostasis and the development and activation of the host immune system. It has been shown that commensal bacterial species can regulate the expression of host genes. 16S rRNA gene sequencing has shown that the microbiota in inflammatory bowel disease (IBD) is abnormal and characterized by reduced diversity. MicroRNAs (miRNAs) have been explored as biomarkers and therapeutic targets, since they are able to regulate specific genes associated with Crohn's disease (CD). In this work, we aim to investigate the composition of gut microbiota of active treatment-naïve adult CD patients, with miRNA profile from gut microbiota.To investigate the composition of gut microbiota of active treatment-naïve adult CD patients, with miRNA profile from gut microbiota.AIMTo investigate the composition of gut microbiota of active treatment-naïve adult CD patients, with miRNA profile from gut microbiota.Patients attending the outpatient clinics at Valme University Hospital without relevant co-morbidities were matched according to age and gender. Faecal samples of new-onset CD patients, free of treatment, and healthy controls were collected. Faecal samples were homogenized, and DNA was amplified by PCR using primers directed to the 16S bacterial rRNA gene. Pyrosequencing was performed using GS-Junior platform. For sequence analysis, MG-RAST server with the database Ribosomal Project was used. MiRNA profile and their relative abundance were analyzed by quantitative PCR.METHODSPatients attending the outpatient clinics at Valme University Hospital without relevant co-morbidities were matched according to age and gender. Faecal samples of new-onset CD patients, free of treatment, and healthy controls were collected. Faecal samples were homogenized, and DNA was amplified by PCR using primers directed to the 16S bacterial rRNA gene. Pyrosequencing was performed using GS-Junior platform. For sequence analysis, MG-RAST server with the database Ribosomal Project was used. MiRNA profile and their relative abundance were analyzed by quantitative PCR.Microbial community was characterized using 16S rRNA gene sequencing in 29 samples (n = 13 CD patients, and n = 16 healthy controls). The mean Shannon diversity was higher in the healthy control population compared to CD group (5.5 vs 3.7). A reduction in Firmicutes and an increase in Bacteroidetes were found. Clostridia class was also significantly reduced in CD. Principal components analysis showed a grouping pattern, identified in most of the subjects in both groups, showing a marked difference between control and CD groups. A functional metabolic study showed that a lower metabolism of carbohydrates (P = 0.000) was found in CD group, while the metabolism of lipids was increased. In CD patients, three miRNAs were induced in affected mucosa: mir-144 (6.2 ± 1.3 fold), mir-519 (21.8 ± 3.1) and mir-211 (2.3 ± 0.4).RESULTSMicrobial community was characterized using 16S rRNA gene sequencing in 29 samples (n = 13 CD patients, and n = 16 healthy controls). The mean Shannon diversity was higher in the healthy control population compared to CD group (5.5 vs 3.7). A reduction in Firmicutes and an increase in Bacteroidetes were found. Clostridia class was also significantly reduced in CD. Principal components analysis showed a grouping pattern, identified in most of the subjects in both groups, showing a marked difference between control and CD groups. A functional metabolic study showed that a lower metabolism of carbohydrates (P = 0.000) was found in CD group, while the metabolism of lipids was increased. In CD patients, three miRNAs were induced in affected mucosa: mir-144 (6.2 ± 1.3 fold), mir-519 (21.8 ± 3.1) and mir-211 (2.3 ± 0.4).Changes in microbial function in active non-treated CD subjects and three miRNAs in affected vs non-affected mucosa have been found. miRNAs profile may serve as a biomarker.CONCLUSIONChanges in microbial function in active non-treated CD subjects and three miRNAs in affected vs non-affected mucosa have been found. miRNAs profile may serve as a biomarker.
Author Romero-García, Teresa
Rojas-Feria, María
Fernández Caballero-Rico, Jose Ángel
Avilés-Recio, Marta
García, Federico
Chueca Porcuna, Natalia
Castro-Fernandez, Manuel
Del Campo, José A
Pastor Ramírez, Helena
Romero-Gόmez, Manuel
Grande, Lourdes
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Keywords microRNAs
Bacteroidetes
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Crohn’s disease
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Supported by Instituto de Salud Carlos III, and Consejería de Salud Junta de Andalucía PI14/01349.
Author contributions: Rojas-Feria M, Romero-García T, Romero-Gómez M, García F, Grande L and Del Campo JA; designed the study and wrote the manuscript. Fernández Caballero-Rico JÁ, Pastor Ramírez H and Avilés-Recio M; analyzed the data. Rojas-Feria M, Castro-Fernández M, Chueca Porcuna N, Grande L and Del Campo JA; contributed to perform experiments and data analysis
Telephone: +34-95-5015485
Corresponding author to: José A Del Campo, PhD, Senior Scientist, Department of Digestive Diseases, Valme University Hospital, UGC Digestive Disease and CIBERehd, Servicio Andaluz de Salud, Avda. Bellavista s/n, Sevilla E-41014, Spain. jantonio.delcampo@ciberehd.org
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Title Modulation of faecal metagenome in Crohn’s disease: Role of microRNAs as biomarkers
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