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Landmark Crohn’s Microbiome Study Yields Important Findings
"One of the largest microbiome-focused studies to date has identified several distinct microbial species and communities that correlate with both the presence and severity of Crohn’s disease.
The findings, which analyzed the microbiome of 447 treatment-naive pediatric patients with Crohn’s disease and 221 without the condition, could pave the way for microbiome-based diagnostics and therapies for the illness, one expert said.
“This was an excellent study, both in terms of its design and implications,” said Colleen Kelly, MD, assistant professor of medicine at Warren Alpert Medical School of Brown University, in Providence, R.I., who was not involved in the research. “Clinically, the findings suggest we may eventually be able to use specific bacterial taxa as biomarkers to more reliably diagnose Crohn’s disease, and that these biomarkers could be derived from rectal tissue biopsies obtained through minimally invasive methods such as proctoscopy.”
Senior investigator Ramnik Xavier, MD, professor of medicine, chief of the gastrointestinal unit and director of the Center for the Study of Inflammatory Bowel Disease at Massachusetts General Hospital, in Boston, and his colleagues at 28 centers in North America genetically sequenced ileal and rectal tissue samples from 447 recently diagnosed Crohn’s patients. The patients had not yet been treated for the disease, although 57 had previously received antibiotics for other indications. The researchers also collected fecal samples from 233 of these individuals.
The 221 control patients did not have inflammatory conditions but some presented with gastrointestinal symptoms.
Tissue sample analyses revealed that children with Crohn’s generally had less species diversity, according to the researchers. Crohn’s disease also was associated with smaller populations of Erysipelotrichales, Bacteroidales and Clostridiales and larger populations of Enterobacteriaceae, Pasteurellaceae, Veillonellaceae and Fusobacteriaceae, the latter of which is associated with colorectal carcinoma (Genome Res 2012;22:292-298).
Based on the patterns they uncovered, Dr. Xavier and his colleagues developed and tested the Microbial Dysbiosis Index (MD-Index), which uses the presence and density of specific microbial populations as variables. They found that higher scores on the MD-Index, which reflect reduced species diversity and greater microbial dysbiosis, strongly correlated with disease severity as measured by the Pediatric CD Activity Index (PCDAI). A higher MD-Index also strongly correlated with the presence of several serological markers of Crohn’s activity.
“The association suggests that there is a potential link between the presence of these microbes and the serologic biomarkers, but that needs to be determined in future studies,” said Dr. Xavier, who presented the study at Digestive Disease Week 2014 (abstract 850a). Detailed results related to the serology-microbial link will be reported in an upcoming publication, he added.
In the subgroup of patients who had received antibiotics for indications other than Crohn’s disease, Dr. Xavier’s team found more pronounced microbial dysbiosis. That finding is consistent with prior epidemiologic and clinical research, he said (see, e.g., Gut 2011;60:49-54).
Dr. Kelly said this finding is clinically significant, given that antibiotics are commonly used as treatment for Crohn’s.
“The result suggests that antibiotic therapy in Crohn’s disease may not always be beneficial and it helps explain why there is a higher risk of Clostridium difficile infection in [irritable bowel disease] patients,” she said.
The researchers effectively enlarged their study population to more than 1,500 by sequencing samples from several other Crohn’s study cohorts. Individuals in those cohorts had longer disease duration (mean seven years), were older (mean age 41 years) and some had received treatment for their illness. That analysis confirmed their findings, they said."
http://m.gastroendonews.com/Article.aspx?d=In+the+News&d_id=187&i=October+2014&i_id=1115&a_id=28479
"One of the largest microbiome-focused studies to date has identified several distinct microbial species and communities that correlate with both the presence and severity of Crohn’s disease.
The findings, which analyzed the microbiome of 447 treatment-naive pediatric patients with Crohn’s disease and 221 without the condition, could pave the way for microbiome-based diagnostics and therapies for the illness, one expert said.
“This was an excellent study, both in terms of its design and implications,” said Colleen Kelly, MD, assistant professor of medicine at Warren Alpert Medical School of Brown University, in Providence, R.I., who was not involved in the research. “Clinically, the findings suggest we may eventually be able to use specific bacterial taxa as biomarkers to more reliably diagnose Crohn’s disease, and that these biomarkers could be derived from rectal tissue biopsies obtained through minimally invasive methods such as proctoscopy.”
Senior investigator Ramnik Xavier, MD, professor of medicine, chief of the gastrointestinal unit and director of the Center for the Study of Inflammatory Bowel Disease at Massachusetts General Hospital, in Boston, and his colleagues at 28 centers in North America genetically sequenced ileal and rectal tissue samples from 447 recently diagnosed Crohn’s patients. The patients had not yet been treated for the disease, although 57 had previously received antibiotics for other indications. The researchers also collected fecal samples from 233 of these individuals.
The 221 control patients did not have inflammatory conditions but some presented with gastrointestinal symptoms.
Tissue sample analyses revealed that children with Crohn’s generally had less species diversity, according to the researchers. Crohn’s disease also was associated with smaller populations of Erysipelotrichales, Bacteroidales and Clostridiales and larger populations of Enterobacteriaceae, Pasteurellaceae, Veillonellaceae and Fusobacteriaceae, the latter of which is associated with colorectal carcinoma (Genome Res 2012;22:292-298).
Based on the patterns they uncovered, Dr. Xavier and his colleagues developed and tested the Microbial Dysbiosis Index (MD-Index), which uses the presence and density of specific microbial populations as variables. They found that higher scores on the MD-Index, which reflect reduced species diversity and greater microbial dysbiosis, strongly correlated with disease severity as measured by the Pediatric CD Activity Index (PCDAI). A higher MD-Index also strongly correlated with the presence of several serological markers of Crohn’s activity.
“The association suggests that there is a potential link between the presence of these microbes and the serologic biomarkers, but that needs to be determined in future studies,” said Dr. Xavier, who presented the study at Digestive Disease Week 2014 (abstract 850a). Detailed results related to the serology-microbial link will be reported in an upcoming publication, he added.
In the subgroup of patients who had received antibiotics for indications other than Crohn’s disease, Dr. Xavier’s team found more pronounced microbial dysbiosis. That finding is consistent with prior epidemiologic and clinical research, he said (see, e.g., Gut 2011;60:49-54).
Dr. Kelly said this finding is clinically significant, given that antibiotics are commonly used as treatment for Crohn’s.
“The result suggests that antibiotic therapy in Crohn’s disease may not always be beneficial and it helps explain why there is a higher risk of Clostridium difficile infection in [irritable bowel disease] patients,” she said.
The researchers effectively enlarged their study population to more than 1,500 by sequencing samples from several other Crohn’s study cohorts. Individuals in those cohorts had longer disease duration (mean seven years), were older (mean age 41 years) and some had received treatment for their illness. That analysis confirmed their findings, they said."
http://m.gastroendonews.com/Article.aspx?d=In+the+News&d_id=187&i=October+2014&i_id=1115&a_id=28479
