Study identifies distinct microbiome in Crohn’s intestinal submucosa

A study that evaluated bacterial populations present in the submucosal intestinal tissue of patients with Crohn’s and controls provides evidence suggesting there may be "at least two distinct populations or biotypes within the Crohn’s disease spectrum and the existence of a submucosal microbiome in both health and disease," according to the investigators.

"Our results, if corroborated by larger population studies and development of methodologies applicable to a clinical setting, could revolutionize the diagnosis, management, and treatment of Crohn’s disease," Rodrick J. Chiodini, Ph.D., and his coauthors concluded in the study, which was published in August (J. Clin. Gastroenterol. 2013; 47:612-20). "It would allow the identification of patient subpopulations and biotypes within the Crohn’s disease spectrum and the application of targeted chemotherapeutic treatments that go beyond supportive in nature," they added.

The study compared submucosal intestinal tissue samples of 14 patients with Crohn’s disease obtained during surgery with that of six patients undergoing intestinal surgery for reasons that did not include inflammatory bowel disease. To detect the presence of bacterial pathogens, they evaluated submucosal intestinal tissue that was directly associated with intestinal inflammation and compared the findings to those of the mucosal lining, using quantitative genetic methods that detected 32 virulence- and transposon-associated genes and to determine total submucosal bacterial counts.

"The ability to subgroup patient populations may have a profound effect on the diagnosis, management, and ultimate cure of the disease."

They determined that there was a "normal" submucosal bacterial community (microbiome) in both health and disease that was different from the bacteria present in the mucosal and luminal populations, Dr. Chiodini explained in an interview. They also determined that total bacterial counts within the diseased Crohn’s tissues were several hundredfold higher than the counts found in normal tissue, added Dr. Chiodini, formerly of the department of internal medicine, Texas Tech University Health Sciences Center, El Paso.

In addition to increased total submucosal bacteria counts, Proteobacteria-associated adherence/virulence genes were detected in the submucosa of 43% of patients with Crohn’s disease, a statistical significantly higher rate when compared with that from the mucosa of the same patient and controls. Mycobacterium-associated* transposons were detected in the submucosa of 50% of the patients with Crohn’s disease, also at a significantly higher rate than the mucosa and controls.

These biotypes were found to be mutually exclusive: Invasion/adherence genes were not found in patients in which Mycobacterium-associated* transposons were detected and vice versa, Dr. Chiodini said in the interview.

"There is now overwhelming evidence that enteric bacteria play a major role in the pathogenesis of Crohn’s disease, either as causative agents or mitigating factors," he added. "As such, a great deal of effort has been devoted to the examination of the bacteria present within the intestinal lumen and associated with the mucosal lining of the intestine."

This study is the first to look at bacterial populations within the submucosa, where the inflammation is actually occurring, he noted.

While their results need to be corroborated with larger patient populations, "the data presented herein also provide the first objective evidence that Crohn’s disease may not have a single etiology," he continued. "The ability to subgroup patient populations may have a profound effect on the diagnosis, management, and ultimate cure of the disease. If clinicians can gain a better understanding of the microbes that are directly associated with intestinal inflammation, it will give them a greater understanding of the intestinal ecology and allow them to better manage the inflammation, thereby improving the prognosis of patients."

Dr. Chiodini has recently relocated to St. Vincent’s Health Care and Montana State University, Billings.

None of the authors had disclosures. The study was supported in part by the Texas Tech University Health Sciences Center, the Lizanell and Colbert Coldwell Foundation, the CAMC Health Education and Research Institute, and the Crohn’s Disease Initiative.

[email protected]

*Correction 8/20/2013: An earlier version of this story missnamed the bacteria.

A study that evaluated bacterial populations present in the submucosal intestinal tissue of patients with Crohn’s and controls provides evidence suggesting there may be "at least two distinct populations or biotypes within the Crohn’s disease spectrum and the existence of a submucosal microbiome in both health and disease," according to the investigators.

"Our results, if corroborated by larger population studies and development of methodologies applicable to a clinical setting, could revolutionize the diagnosis, management, and treatment of Crohn’s disease," Rodrick J. Chiodini, Ph.D., and his coauthors concluded in the study, which was published in August (J. Clin. Gastroenterol. 2013; 47:612-20). "It would allow the identification of patient subpopulations and biotypes within the Crohn’s disease spectrum and the application of targeted chemotherapeutic treatments that go beyond supportive in nature," they added.

The study compared submucosal intestinal tissue samples of 14 patients with Crohn’s disease obtained during surgery with that of six patients undergoing intestinal surgery for reasons that did not include inflammatory bowel disease. To detect the presence of bacterial pathogens, they evaluated submucosal intestinal tissue that was directly associated with intestinal inflammation and compared the findings to those of the mucosal lining, using quantitative genetic methods that detected 32 virulence- and transposon-associated genes and to determine total submucosal bacterial counts.

"The ability to subgroup patient populations may have a profound effect on the diagnosis, management, and ultimate cure of the disease."

They determined that there was a "normal" submucosal bacterial community (microbiome) in both health and disease that was different from the bacteria present in the mucosal and luminal populations, Dr. Chiodini explained in an interview. They also determined that total bacterial counts within the diseased Crohn’s tissues were several hundredfold higher than the counts found in normal tissue, added Dr. Chiodini, formerly of the department of internal medicine, Texas Tech University Health Sciences Center, El Paso.

In addition to increased total submucosal bacteria counts, Proteobacteria-associated adherence/virulence genes were detected in the submucosa of 43% of patients with Crohn’s disease, a statistical significantly higher rate when compared with that from the mucosa of the same patient and controls. Mycobacterium-associated* transposons were detected in the submucosa of 50% of the patients with Crohn’s disease, also at a significantly higher rate than the mucosa and controls.

These biotypes were found to be mutually exclusive: Invasion/adherence genes were not found in patients in which Mycobacterium-associated* transposons were detected and vice versa, Dr. Chiodini said in the interview.

"There is now overwhelming evidence that enteric bacteria play a major role in the pathogenesis of Crohn’s disease, either as causative agents or mitigating factors," he added. "As such, a great deal of effort has been devoted to the examination of the bacteria present within the intestinal lumen and associated with the mucosal lining of the intestine."

This study is the first to look at bacterial populations within the submucosa, where the inflammation is actually occurring, he noted.

While their results need to be corroborated with larger patient populations, "the data presented herein also provide the first objective evidence that Crohn’s disease may not have a single etiology," he continued. "The ability to subgroup patient populations may have a profound effect on the diagnosis, management, and ultimate cure of the disease. If clinicians can gain a better understanding of the microbes that are directly associated with intestinal inflammation, it will give them a greater understanding of the intestinal ecology and allow them to better manage the inflammation, thereby improving the prognosis of patients."

Dr. Chiodini has recently relocated to St. Vincent’s Health Care and Montana State University, Billings.

None of the authors had disclosures. The study was supported in part by the Texas Tech University Health Sciences Center, the Lizanell and Colbert Coldwell Foundation, the CAMC Health Education and Research Institute, and the Crohn’s Disease Initiative.

[email protected]

*Correction 8/20/2013: An earlier version of this story missnamed the bacteria.

A study that evaluated bacterial populations present in the submucosal intestinal tissue of patients with Crohn’s and controls provides evidence suggesting there may be "at least two distinct populations or biotypes within the Crohn’s disease spectrum and the existence of a submucosal microbiome in both health and disease," according to the investigators.

"Our results, if corroborated by larger population studies and development of methodologies applicable to a clinical setting, could revolutionize the diagnosis, management, and treatment of Crohn’s disease," Rodrick J. Chiodini, Ph.D., and his coauthors concluded in the study, which was published in August (J. Clin. Gastroenterol. 2013; 47:612-20). "It would allow the identification of patient subpopulations and biotypes within the Crohn’s disease spectrum and the application of targeted chemotherapeutic treatments that go beyond supportive in nature," they added.

The study compared submucosal intestinal tissue samples of 14 patients with Crohn’s disease obtained during surgery with that of six patients undergoing intestinal surgery for reasons that did not include inflammatory bowel disease. To detect the presence of bacterial pathogens, they evaluated submucosal intestinal tissue that was directly associated with intestinal inflammation and compared the findings to those of the mucosal lining, using quantitative genetic methods that detected 32 virulence- and transposon-associated genes and to determine total submucosal bacterial counts.

"The ability to subgroup patient populations may have a profound effect on the diagnosis, management, and ultimate cure of the disease."

They determined that there was a "normal" submucosal bacterial community (microbiome) in both health and disease that was different from the bacteria present in the mucosal and luminal populations, Dr. Chiodini explained in an interview. They also determined that total bacterial counts within the diseased Crohn’s tissues were several hundredfold higher than the counts found in normal tissue, added Dr. Chiodini, formerly of the department of internal medicine, Texas Tech University Health Sciences Center, El Paso.

In addition to increased total submucosal bacteria counts, Proteobacteria-associated adherence/virulence genes were detected in the submucosa of 43% of patients with Crohn’s disease, a statistical significantly higher rate when compared with that from the mucosa of the same patient and controls. Mycobacterium-associated* transposons were detected in the submucosa of 50% of the patients with Crohn’s disease, also at a significantly higher rate than the mucosa and controls.

These biotypes were found to be mutually exclusive: Invasion/adherence genes were not found in patients in which Mycobacterium-associated* transposons were detected and vice versa, Dr. Chiodini said in the interview.

"There is now overwhelming evidence that enteric bacteria play a major role in the pathogenesis of Crohn’s disease, either as causative agents or mitigating factors," he added. "As such, a great deal of effort has been devoted to the examination of the bacteria present within the intestinal lumen and associated with the mucosal lining of the intestine."

This study is the first to look at bacterial populations within the submucosa, where the inflammation is actually occurring, he noted.

While their results need to be corroborated with larger patient populations, "the data presented herein also provide the first objective evidence that Crohn’s disease may not have a single etiology," he continued. "The ability to subgroup patient populations may have a profound effect on the diagnosis, management, and ultimate cure of the disease. If clinicians can gain a better understanding of the microbes that are directly associated with intestinal inflammation, it will give them a greater understanding of the intestinal ecology and allow them to better manage the inflammation, thereby improving the prognosis of patients."

Dr. Chiodini has recently relocated to St. Vincent’s Health Care and Montana State University, Billings.

None of the authors had disclosures. The study was supported in part by the Texas Tech University Health Sciences Center, the Lizanell and Colbert Coldwell Foundation, the CAMC Health Education and Research Institute, and the Crohn’s Disease Initiative.

[email protected]

*Correction 8/20/2013: An earlier version of this story missnamed the bacteria.