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Advanced Metagenomic Analysis of Human Gastrointestinal Microbiota in Patients With Chronic GI Disorders (IBS, IBD, CRC)

16 Years
65 Years
Not Enrolling
Irritable Bowel Syndrome, Colitis, Ulcerative, Crohn Disease, Adenomatous Polyps, Colonic Neoplasm

Thank you

Trial Information

Advanced Metagenomic Analysis of Human Gastrointestinal Microbiota in Patients With Chronic GI Disorders (IBS, IBD, CRC)

The terms intestinal "microflora" or "microbiota" refer to the microbial ecosystem
colonizing the gastrointestinal tract. Recently developed molecular biology instruments
suggest that a substantial part of bacterial communities within the human gut still have to
be described. Intestinal bacteria play an essential role in the development and homeostasis
of the immune system. Most of these important microbiota are unculturable which
significantly have limited our understanding of bacterial-host crosstalk. Among the methods
designed to gain access to the physiology and genetics of uncultured organisms,
metagenomics, the genomic analysis of a population of microorganisms, has emerged as a
powerful technology. Metagenomics is the study of genomic content in a complex mixture of
microorganisms. Direct isolation of genomic DNA from an environment circumvents culturing
the organisms under study. The two primary goals of this approach are to develop a consensus
of what populations of microorganisms are presents and then to identify what roles each
microorganism has within a specific environment. Metagenomics samples are found nearly
everywhere, including several microenvironments within the human gut, soil samples, extreme
environments such as deep mines and the various layers within the ocean. Therefore, the
diversity of microorganisms is thought to be in the range of hundreds of millions to greater
than tens of trillions of species. Among the most mysterious microenvironment is the human
gastrointestinal tract that harbor greater than thousands of millions of microbial species
(at least 1014), including up to 2000 species dominated by anaerobic bacteria.

Many of the gastrointestinal or even other diseases (metabolic as in obesity, or autoimmune
as in allergies) involve primarily the human gut microbiota and then according to specific
changes in microbiota equilibrium certain effects occur on either bowel motility (as in
irritable bowel syndrome: IBS), homeostasis of the GI immune system (as in inflammatory
bowel disease: IBD), or mucosal cells proliferation (as in adenoma - colorectal cancer:
CRC). These chronic diseases affect all nations worldwide and represent a significant public
health burden. They can be seen among children, adolescents, and adults. Currently there is
no medical cure for IBS, IBD or CRC once they develop.

The complex interactions between microbial, genetic, immune, and environmental factors seem
to play an important role in the pathogenesis of IBS, IBD and CRC. Lately, post infectious -
IBS have gained increasing focus, to the extent that whole pathogenesis of IBS might be
attributed to a specific triggering factor of microbiota balance. The prevailing theory is
that IBD is related to an altered mucosal barrier with a deregulated immune response
directed against specific modifications in the normal microbiota leading to the alteration
of its equilibrium. The etiology of IBD can therefore be conceptualized as an aberrant
immunologic response to a modified component or components of the gut microbiota potentially
following an environmental insult. Likewise, CRC development process from normal mucosal
surface to adenoma and finally to CRC; is probably related to gut microbiota.

The prevalence of these diseases has been documented to go through an obvious increase in
Saudi Arabia during the last 2 decades. This would represent a unique model to study the
role of GIT microbiota or their metagenomics and their modifications in response to
environmental or dietary factors in this community that went into urbanization fairly
recently, and then analyze their causative relations to the focus diseases.

Here, we propose to perform a comprehensive analysis of the gastrointestinal tract
microbiota and its contribution on gut homeostasis in normal subjects and patients with IBS,
IBD and CRC by using state of the art metagenomics technology. This will be done on a Saudi
population sample that we believe represent a unique model.

Our specific objectives for this project are:

- Characterize the microbiota composition (microbes and virus) of the mucosa from Saudi
patients with IBS, IBD and CRC.

- Characterize the mobile GI metagenomics of Saudi patients with IBS, IBD and CRC.

- Compare the metagenomics of IBS, IBD and CRC patients to each other and to normal
subjects from the same population.

Expected outcomes and Significance of research:

Altogether, the results from aims 1 and 2 will provide for the first time a comprehensive
and in-depth analysis of the mucosa-associated microbiota of adult patients with IBS, IBD
and CRC in Saudi population. The proposed study will define a microbiota "fingerprint" for
Saudi norms, IBS, IBD and CRC. The contribution of virome and the mobile metagenome into
these diseases development and/or health maintenance will be assessed for the first time and
thus has the potential to reveal new paradigms. In addition, the study of the virome and
mobile metagenome will help us to understand the selective forces that could contribute to
the alteration and evolution of the microbiota community and thus could have important
implications for the treatment of the diseases. Certainly, the work proposed here will pave
the way toward future hypothesis-driven research which could lead to the design of
therapeutic strategies aimed at manipulating the microbial community.

Inclusion Criteria:

IBS: 25 consecutive patients presenting to KFMC GI service after launching the project on
Jan 2010, will be recruited if they meet the following conditions:

1. Meet the diagnostic criteria as per ROME-II classification and as judged by
experienced consultants for not less than 5 years.

2. IBS with diarrhea or constipation or mixed predominance pattern will be included.

3. Standard diagnostic tests have to be done to exclude any possible organic lesion to
explain the abdominal pain, and all have to be negative.

IBD: from the KFMC GI service database, 25 Ulcerative Colitis (UC) and 25 Crohn's Disease
(CD) will be selected according to following:

1. Confirmed diagnosis as CD or UC based on clinical, endoscopic and histological

2. Specifically did not use antibiotics for last 6 months before enrollment.

3. Detailed information about current treatment regimen has to be provided, and current
use of 5-ASA, Steroid or Azathioprine will not hold from enrolling the patients as we
cannot have patients off any one or more of these medications. (Obviously, we cannot
exclude effects of these medications on microbiota, but it is not the focus of the
current study).

4. None of the patients selected would be on anti-TNF medications. CRC: 25 consecutive
cases of confirmed CRC and 25 consecutive cases of adenomatous CR polyposis as per
histological diagnosis made by 2 experienced pathologists will be included.

Normal Subjects: 25 normal control groups that are matched for age and sex to the other 3
disease groups will be selected from consecutive CRC screening colonoscopy subjects who
get referred to KFMC GI service during the study period, and proved to have no GI
disorders. 15 will be selected from Urban and 10 from Rural areas of KSA.

Exclusion Criteria:

1. Treatment with antibiotics for the last 6 months before enrollment.

2. Absence of recent infective colitis, bowel obstruction, or abdominal surgery.

3. Not on any medication that may affect gut microbiota, like: cholestyramine,
ursodeoxycholic acid, gut prokinetic agents.

4. Refusal to comply with the unified bowel preparation instructions for all cases.

Type of Study:


Study Design:

Observational Model: Case Control, Time Perspective: Cross-Sectional

Outcome Measure:

mucosa associated microbiota pattern

Outcome Description:

collection of samples as per protocol and characterizing the pattern numerically in each subject of the study groups and compare them to controls

Outcome Time Frame:

one year

Safety Issue:


Principal Investigator

Ahmed O AlOmair, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:



Saudi Arabia: King AbdulAziz City for Science and Technology

Study ID:

09 -116



Start Date:

May 2010

Completion Date:

January 2012

Related Keywords:

  • Irritable Bowel Syndrome
  • Colitis, Ulcerative
  • Crohn Disease
  • Adenomatous Polyps
  • Colonic Neoplasm
  • IBS
  • UC
  • CD
  • CRAP
  • CRC
  • Neoplasms
  • Colitis
  • Colitis, Ulcerative
  • Colonic Neoplasms
  • Crohn Disease
  • Irritable Bowel Syndrome
  • Ulcer
  • Adenomatous Polyps