National Commission on Digestive Diseases (NCDD)
Working Group (WG) Topics and Areas of Overlap
1. Overview of the Digestive System
R. Blumberg, Chair; E. Chang, Vice Chair
Includes development, normal physiology, nutrient and fluid absorption and secretion, GI neurophysiology
and endocrinology, control of eating and satiety, mucosal immunology, microbiology and microbiome.
Note: This working group will address seven areas of basic science. Immediately after each of the seven topic
titles, a number of clinically relevant areas are listed. These clinical areas are meant to serve as examples of
clinical correlates and are not meant to be covered as part of the scope of this WG.
Development (Hirschsprung’s, immunodeficiency, colon cancer, Barrett’s esophagus, pyloric stenosis,
malrotation, biliary atresia, omphalocele, pancreas divisum)
Factors that mediate epithelial-mesenchymal interactions in gastrointestinal (GI) development
Mechanisms of distinction between endoderm derivatives (patterning)
Factors responsible for creating and maintaining crypt-villus integrity and the intestinal stem cell niche
Relation between developmental and oncogenic pathways
Basis of congenital anomalies and metaplastic transformations
Growth/Integrative Physiology (metabolic diseases, intestinal transplantation, tissue engineering,
retroperitoneal fibrosis)
Cross-talk among elements within gut wall and integration with extra-intestinal tissues (e.g., brain)
Interaction between gut and other metabolic tissues—liver, adipose tissue, pancreas, muscle
Integrative response to food intake: coordination of neural, endocrine, muscle, circulatory factors with
epithelial function
Mucosal growth, epithelial turnover, and factors that alter turnover and growth rates under normal
conditions
Role of nutrition in gut development and physiology, including nutritional impacts on gut bacteria
Digestion (malabsorption, nutrition, pernicious anemia, chronic pancreatitis, biliary obstruction, lactase
deficiency, bacterial overgrowth)
Role of membrane transporters in selective uptake and metabolic channeling of lipid macronutrients [fatty
acid (FA), magnesium (MG)] and lipid molecules (sterols, bile acids, xenobiotics)
Dialog between host transporters and bacteria
Enterohepatic circulation and metabolic regulation (satiety, lipid transport, obesity, diabetes, metabolic
syndrome)
Metabolic channeling of FA/sterols and intestinal growth, proliferation, and carcinogenesis
Lipid transporters and antigen presentation
Nutrient and Fluid Absorption/Secretion (diarrhea, short bowel syndrome, radiation, proctitis, gallstones,
celiac sprue)
Regulation of barrier function versus transport
Role of cellular and protein diversity in creating integrated absorptive function
Molecular and functional adaptation of gut to surgical or inflammatory challenge
Identification of receptors and transport proteins controlling micronutrient and macromolecule absorption
Genetic disorders of absorptive pathways
Nutrient absorption regulation in diabetes and obesity
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Neurophysiology, Endocrine, Satiety (gastroparesis, motility disorders, infection and inflammation-induced
motility, visceral hypersensitivity disorders, obesity, swallowing disorders, peptic ulcer disease (PUD),
irritable bowel syndrome (IBS), pancreatic endocrine syndromes)
Enteric nervous system (ENS) neural networks: neurons, interstitial cells of Cajal, smooth muscle and
epithelium
Signal processing in ENS
Interaction between ENS and brain including satiety signals
Afferent signaling in visceral hypersensitivity
Gut peptides/metabolomics and obesity, diabetes, stress and inflammation
Diabetic and age-related apoptosis of ENS
Signaling systems in enteric neurogenesis
Microbiology/Microbiome (post-infectious, gastric cancer, inflammatory bowel disease (IBD), salmonella,
shigella, cytomegalovirus (CMV), H. pylori, cryptosporidiosis, probiotics)
Define bacterially associated diseases by establishing genotype of normal flora
Develop systems for using bacteria as delivery vehicles
Define physiological interactions between host and bacteria
Comparative/evolutionary/environmental microbial ecology definitions
Define how normal flora induces inflammation and what is a “probiotic”
Comparative microbiology of mucosal surfaces
“Bugs” as an organ
Mucosal Immunology (IBS, IBD/inflammation-induced cancer, human immunodeficiency virus
(HIV)/immunodeficiency, transplant/graft-versus-host disease (GVHD), allergy/eosinophilic syndromes,
autoimmune gastritis and hepatitis, imaging of inflammation, celiac sprue)
Mucosal immunization/vaccine development
Mucosal immunoregulation and oral tolerance
Epithelial barrier and host defense immunoglobulin A (IgA) and immunoglobulin G (IgG)
responses/transport
Mucosal cell trafficking
Mucosal cytokine responses
Mucosal immune development
Additional notes:
 Also include physiological factors involved in weight gain, immune response, inflammation, and
cancer as a common mechanism.
 The NIH Roadmap initiative specifically deals with cross-cutting areas, not specific disease areas.
Given its topic area and makeup, this WG has opportunities to identify cross-cutting areas and goals
in basic biology that are not specifically digestive disease-oriented, such as the microbiome, but
which are needed to achieve the goals of the NCDD’s long-range plan.
 Another advantage of this group’s “larger view” is to ensure that the other groups do not overlook
critical topics.
 At the November 6, 2006, meeting, it was suggested that a poster of the basic mechanisms be
developed by a scientific illustrator based on this chapter; the poster could be used in
gastroenterologists’ offices to explain to/educate patients.
 Overlap necessarily occurs between this WG and all others. Dr. Blumberg will recommend his group
members to seek input from Chairs of the other groups to discuss understanding and overlap.
Note: The following chapters differ from WG #1 in that they have a clinical work scope.
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2. Functional Gastrointestinal Disorders and Motility Disorders
K Sanders, Chair; N Norton,
Vice Chair
Includes functional GI disorders, including irritable bowel syndrome, gastroparesis, fecal incontinence,
visceral pain, Hirschsprung’s disease, intestinal pseudo-obstruction, and pelvic floor dysfunction
Functional GI Disorders:
Esophageal disorders (globus; rumination syndrome; functional dysphagia; functional chest pain of
presumed esophageal origin; functional heartburn)
Gastrointestinal disorders (functional dyspepsia, aerophasia, functional vomiting)
Bowel disorders (IBS, functional abdominal bloating, functional constipation, functional diarrhea)
Functional abdominal pain (visceral pain and hypersensitivity; sensory transduction)
Functional disorders of the biliary tract and pancreas (gallbladder dysfunction, sphincter of Oddi
dysfunction)
Anorectal disorders (fecal incontinence, anorectal pain, pelvic floor dyssynergia)
Pediatric disorders (vomiting, abdominal pain, functional diarrhea, disorders of defecation)
Motility Disorders:
Esophagus (achalasia, diffuse esophageal spasm; gastroesophageal reflux disease (GERD) to be in WG 7)
Stomach (gastroparesis, dumping syndrome, cyclic vomiting, vomiting related to pregnancy)
Small intestine (chronic intestinal pseudo-obstruction)
Colon (colonic inertia, functional rectosigmoid obstruction, Hirschsprung’s disease [i.e., altered colonic
motilities])
Conditions that set up overgrowth
Secondary causes of motility problems as result of cancer surgery, obesity surgery, etc. This includes
drugs/narcotics, radiation, post-surgical modifications, structural modifications of the gut (e.g.,
Duncan’s syndrome)
Health disparities: gender, culture, ethnic, socioeconomic
Overlap:
 With WG 7 re esophageal functional and motility disorders and with WG 9 re anorectal disorders
 GERD will be covered by WG 7
 General motility will be covered by WG 1
 Diagnostic and therapeutic tools to be in WG 13
 Normal biology of eating and satiety will be in WG 1
3. Infections of the GI Tract
M Cohen, Chair; R Blumberg, Vice Chair
Includes common bacterial and viral infections, bioterrorism, infections of immunocompromised hosts,
vaccines, probiotics, uncommon diseases (e.g., Whipple’s)
Bacterial pathogens, emerging pathogens, uncommon infections and diseases (e.g., Whipple’s)
Viral pathogens (but viral gastroenteritis in WG 8 re diarrheal diseases)
Parasites, infections in immunocompromised hosts
Vaccines
Probiotics; long-term sequelae of infection, including IBS
Food-borne illnesses; bioterrorism
Host immune responses to infection; microbial agents in the pathogenesis of IBD
Microorganisms and development
Bacterial overgrowth (techniques of diagnosing; the bug rather than the host)
Public health aspects
Agents such as Clostridium difficile
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Overlap:
 With WG 2 re IBS; with WG 5 re IBD and role of microbial species; and with WG 1 re
microorganisms and development; also with WG 8 on gastric and intestinal infections
 With WG 6 re bacterial translocation
 Suggest connect with Dr. Bell and CDC infectious diseases reps
 Will not address mechanisms of secretion or H. pylori
 Transporters will be in WG 8
 Protective factors in human milk, like lactadherin and lactoferrin, oligosaccharides that block
campylobacter, and some of the viruses will be covered in WG 1; overlap with WG 3
 Viral hepatitis will be covered in WG 11
 Imperforate anus and anomalies such as cloaca will be covered re abnormal development in WG 1
4. Cancers of the Digestive System
J Carethers, Chair; R Sandler, Vice Chair
Includes entire GI tract except for liver/biliary. Includes neuroendocrine tumors, pancreatic cancer, and polyp
syndromes; basically, covers each organ once cancer is present; not pre-cancerous conditions
Note: This WG will tackle all forms of cancer that are not included with specific organs. This group should
handle the gastrointestinal stromal tumor (GIST) tumors as well.
Basic mechanisms of digestive cancers (pathogenic mechanisms cutting across all cancers: disregulation of
cell cycle; apoptosis; angiogenesis; ligand/signaling disregulation; nDNA repair; others)
Esophageal cancer (squamous and adenocarcinoma)
Stomach cancer (adenocarcinoma; not H. Pylori (is in WG 8)
Pancreatic cancer (adenocarcinoma and neuroendocrine tumors)
Colorectal neoplasia (colon and rectal precursor lesions and adenocarcinoma)
Cancers of small intestine and cancers involving multiple areas of digestive tract (small intestinal
adenocarcinoma, lymphomas (e.g., mucosa-associated lymphoid tissue (MALT), celiac-related), GI
stomach tumors, carcinoids, etc.)
Overlap:
 Pathogenesis of Barrett’s metaplasia will be in WG 7
 Hepatocellular carcinoma (HCC, gallbladder cancer) will be in WG 11
 Cholangiocarcinoma will be in WG 11
 Pathogenesis of Helicobacter-associated gastric cancer will be in WG 8
 Imaging and WG 13—not resolved
 Adenocarcinoma and IBD-generated cancer, but not ordinary colorectal cancer (will be in WG 4)
 WG 8 will handle Zollinger-Ellison (Z-E) syndrome
 WG 10 may include other pancreatic cancers
Note: Quality of life will be a topic within several groups (e.g., for cancer patients with ostomies).
5. Inflammatory Bowel Diseases
D Podolsky, Chair; E. Chang, Vice Chair
Includes ulcerative colitis, Crohn’s disease, collagenous and microscopic colitis
Epidemiology (epidemiologic or environmental drivers; what can be learned from approaches)
Genetics (susceptibility)
Microbiology (understanding of microflora and relationship to disease processes)
Epithelial biology
Immune responses (innate and adaptive)
Systems biology (multifactorial pathophysiology)
Clinical studies (translation; therapeutics, quality of life, biomarkers to predict recurrence/response to
therapeutics)
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Pediatric IBD (needs and distinctions)
An animal model as a gold standard
Overlap:
 IBD-generated cancer vs. traditional adenocarcinoma (e.g., different pathogenesis with different
genetic pathways. This area should be cross-referenced with WG 4.
 Overlap with WG 1 in multiple areas
 With WG 3 re microbiology and immunology
 With WGs 4, 6, 8, and 11 re clinical aspects
 With WG 13 re imaging
 Coordinate with WG 2 re interface between IBD and IBS
Note: Quality of life will be a topic within several groups (e.g., patients with IBD).
6. Intestinal Failure and Regeneration, Nutritional Disorders and Support, Surgically Modified Gut, and
Transplantation
B Bass, Chair; M Heitkemper, Vice Chair
Includes diseases leading to intestinal failure, oral and parenteral nutrition, obesity, intestinal transplantation,
surgically modified GI tract, and manipulation of absorption, nutrition (e.g., constituents of total parenteral
nutrition [TPN] and enteral nutrition [EN]). Excludes liver/biliary.
Intestinal failure, Surgically Modified Gut, and Transplantation
Management: clinical (nutritional management; maximizing adaptation; development; minimizing
complications—deferring end-stage disease; clinical networks)
Repair: Intestinal adaptation
Epithelial growth and differentiation (stem cells; villus engineering; epithelial matrix interactions)
Manipulations to enhance regeneration (genetic; surgical; target therapeutics)
Replacement: Intestinal transplantation (e.g., transplantation of bowel in children)
Enhancing engraftment—tolerance
Immunologic strategies
Physiology/function of transplanted gut
Long-term sequelae
Surgically modified gut
Bariatric surgery: types of procedures, their physiological basis, short and long-term consequences
Could include other types of surgically modified gut, but these are much less common
Nutritional Disorders and Support: Nutrition per se will not be covered; will address nutritional support of
specific digestive disorders
Overlap:
 WG 1 Overview. WG 1 will cover physiological factors involved in weight gain re understanding
normal physiology of eating and control of eating behavior and satiety
 With WG 8 for diseases that lead to intestinal failure
 With WG 5 re IBD
 With WG 11 for Disease of the Liver and Biliary
 With WG 13 re tissue engineering
 WG 6 will cover tissue repair and adaptation and short bowel (rather than WG 8)
 WG 6 will cover bacterial translocation including that affecting the pancreas
 With WG 12 re autonomic neuropathy
Note: Quality of life will be a topic within several groups (e.g., for patients with surgically modified gut or
transplantation).
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7. Diseases of the Oropharynx and Esophagus
P. J. Pasricha, Chair; D. Lieberman, Vice Chair
Includes GERD, feeding and swallowing disorders, Barrett’s esophagus (to be integrated with cancer working
group), and eosinophilic esophagitis and other eosinophilic GI disorders
Oropharynx: Mainly swallowing disorders
Structural (diverticula, cricoropharyngeal bar)
Functional (neurological and muscular diseases)
Esophagus:
GERD and related complications (Barrett’s)
Motor disorders (achalasia, diffuse esophageal spasm [DES])
Sensory disorders (non-cardiac chest pain)
Inflammatory and infectious (eosinophilic esophagitis; candida, herpes simplex virus [HSV], CMV, HIV;
autoimmune [scleroderma])
Pediatric disorders such as swallowing disorders in children with developmental disabilities and also
esophageal problems in children (a pediatric gastroenterologist is a member of the WG)
Overlap:
 With WG 1 Overview
 With WG 2 re Motility
 With WG 4 re Cancers
 With WG 3 re Infections
 With WG 13 re Endoscopy and Imaging Technology
 Opportunistic infections will be covered by WG 3 Infections of the GI Tract
 Systemic disorders will be covered in WG 12
 Scleroderma will be covered in WG 12 as a cross-cutting area
8. Diseases of the Stomach and Small Bowel
E Chang, Chair; M Cerulli, Vice Chair
Includes diseases of the stomach and small bowel, including H. pylori, acid-peptic diseases, autoimmune,
celiac disease, ischemic conditions, enzymatic deficiencies, and transport defects
Acid-peptic diseases (H. pylori-induced peptic ulcer, nonsteroidal anti-inflammatory drugs [NSAIDs] and GI
bleeding, Zollinger-Ellison syndrome, Menetrier’s, infections [viral, opportunitstic; CMV, herpes simplex
1, and possibly Crohn's], inflammatory [celiac disease])
Transport, malabsorption, and maldigestion (acute diarrheal diseases, chronic diarrheal diseases,
malabsorptive/maldigestive disorders (nutrients; but not maldigestion secondary to pancreatic
insufficiency), enzyme deficiencies [lactase, enteropeptidase, etc.], transport defects, bacterial
overgrowth)
Celiac disease, other inflammation diseases and disorders (celiac sprue, necrotizing enterocolitis [NEC],
pediatric disorders [congenital, genetic; necrotizing enterocolitis], eosinophilic gastroenteritis [GE],
others [radiation enteritis, GI bleeding, obstruction, cystic fibrosis (CF) re digestive tract only not
pancreatic])
Animal models re celiac disease and eosinophilic disorders
Overlap:
 With WG 1 Overview
 With WG 3 re bacterial overgrowth, viral GE, and bacterial pathogens
 With WG 6 re tissue repair/adaptation and short bowel and bacterial translocation
 With WG 2 re IBS and small bowel overgrowth
 With WG 7 re GERD and WG 9 re diarrheal diseases, pediatric disorders, and transport
 With WG 5 re gastric and small bowel disorders
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With WG 10 re enteropeptidase and CF [
With WG 13 re endoscopic therapy and imaging
GI bleeding is a cross-cutting issue (variceal bleeding as well as non-variceal, gastroesophageal versus
small bowel versus colonic)
9. Diseases of the Colon and Rectum
J Wilson, Chair; N Norton, Vice Chair
Includes diverticular disease, ischemic colitis, hemorrhoids, anorectal diseases such as solitary rectal ulcers
and radiation proctitis (preneoplastic to be integrated with cancer working group)
Colonic mucosal injury and repair (colonic mucosal absorption; role of NSAIDS, other agents; role of gut
microflora)
Colonic wall—diverticuli, pathogenesis
Colon vasculature and ischemia
Diverticular disease (interaction with gut flora; pathogenesis of inflammation, bleeding, segmental
inflammation; management)
Ischemic colitis (pathogenesis, treatment)
Radiation colitis (pathogenesis, treatment, prevention)
Angioectasias (pathogenesis, prevention)
Solitary colon ulcers
Anorectal disease: hemorrhoids, fissures, fistulas (pathogenesis and therapy; association with incontinence)
Foreign bodies
Vater syndrome and perforated anus
Appendicitis
Overlap:
 With WG 3 re gastrointestinal infections
 With WG 2 re gastrointestinal motility, constipation; functional bowel disorders, IBS, fecal
incontinence, pelvic floor dysfunction
 With WG 5 re inflammatory bowel disease—ulcerative colitis (UC), Crohn’s, microscopic colitis
 With WG 13 Bioengineering, Biotechnology, and Imaging re GI bleeding, fecal incontinence
10. Diseases of the Pancreas (not diabetes)
J Holt, Chair; P J Pasricha, Vice Chair
Includes acute and chronic pancreatitis, endocrine syndromes (excluding diabetes), cystic fibrosis, cystic
lesions (including cystic neoplasms)
Mechanisms of acute pancreatic injury and complications (natural history, major etiologies [alcohol effects,
gallstone pancreatitis], systemic effects, major complications [necrotizing pancreatitis and multiple organ
failure])
Mechanisms of chronic pancreatitis and complications (natural history, etiology, chronic and hereditary
pancreatitis, pain, therapeutic approaches, cystic fibrosis related to exocrine pancreas)
Quality of life
Pancreatic disease in children (epidemiology, natural history, and genetics)
Diagnosis and treatment of acute pancreatitis (clinical studies)
Diagnosis and treatment of chronic pancreatitis (clinical studies)
Overlap:
 Basic pancreatic biology will be in WG 1 Overview, including digestion and development, endocrine
integrated physiology, physiology of normal state vs. disease state
 With WG 4 re intra-pancreatic mucosal (IPM) lesions associated with development into cancer; also
neuroendrocrine will be in WG 4
 Adenocarninomas will be in WG 4, with possibly some orphan ones in WG 12
 Endocrine Z-E and other endocrine tumors related to diarrheal diseases will be in WG 8 Stomach and
Small Bowel
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Cystic fibrosis re involvement of digestive tract will be in WG 8 but not pancreatic CF
CF-related malabsorptive/maldigestive complications will be in WG 10, specifically maldigestion
secondary to pancreatic insufficiency
WG10 will cover benign cystic diseases and cystic neoplasia
11. Diseases of the Liver and Biliary System
(Integrate with Action Plan for Liver Disease Research)
B Bacon, Chair; M Cerulli, Vice Chair
Epidemiology, natural history
Causes of chronic liver and biliary diseases
Pathophysiologic mechanisms
Genetics
Treatment paradigms
Clinical trials
Liver transplantation
Pediatric liver disease (e.g., Wilson disease)
Autoimmune liver diseases and liver transplantation
Liver and gall bladder cancer
Alcoholic liver disease and fatty liver disease
HIV and liver disease
Fibrogenesis and other complications of chronic liver disease.
Hemachromatosis (note: this topic in particular is well covered in the Action Plan for Liver Disease Research)
Viral hepatitis
Portal hypertension and variceal bleeding, whether esophageal or gastric, as complication of end-stage liver
Quality of life and symptom management for patients undergoing treatment for liver diseases.
Overlap areas:
 Fundamental mechanisms with WG 1
 Imaging of liver lesions with WG 13
 Therapy of portal hypertension and endoscopic area, although not all therapy is endoscopic
12. Multi-Organ Diseases and Diseases of Abdominal Structures D Lieberman, Chair; S James, Co-Chair
Includes diseases of abdominal structures: mesentery, omentum abdominal wall, retroperitoneal fibrosis. Also
includes scleroderma, sarcoidosis, hemochromatosis, and metabolic diseases such as amyloidosis
Diseases of abdominal cavity (hernia, volvulus)
GI manifestations of systemic conditions
Genetic connective tissue diseases (Ehlers-Danlos, etc.)
Rheumatological diseases (scleroderma, vasculitis)
Endocrine diseases (diabetes)
Metabolic disorders (amyloidosis)
Toxic diseases/disorders (heavy metals)
Idiopathic diseases/disorders (sarcoidosis, retroperitoneal fibrosis)
Neurological disorders (re effects on GI system: stroke; autonomic neuropathy, Parkinson’s)
Vascular disorders
Aging gut
GI issues in pregnancy
Overlap:
 With WG 4 re lymphomas
 With WG 6 re autonomic neuropathy
 With WG 11 for liver diseases of pregnancy
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13. Bioengineering, Biotechnology, and Imaging
B Bass, Chair; D Lieberman, Vice Chair
Includes endoscopic technologies, surgical technologies, imaging technology, bioartificial support devices
and artificial tissues, electrical pacing/stimulators, and diagnostic devices
Luminal disease (surveillance and detection; ablation technologies and applications)
Intra-abdominal disease (disease detection and surveillance; procedural planning and guidance; interventional
technologies)
Tissue-organ replacement
Imaging (virtual endoscopy; Image enhancement—targeted procedural intervention/detection; I\image
guidance—surgical/procedural; molecular imaging for digestive disorders [cancer; IBD])
Tissue engineering (stem cells; scaffolds; growth and differentiation; functional replacement of organs)
Emerging technologies (robotics; remote control devices; image guidance; molecular targets; functional
imaging interface)
Devices (tools; ablation; remote control devices; miniaturization)
Note: this topic is relevant to all digestive diseases and is mutlidisciplinary (imaging, radiology, engineering,
mathematics, and computational science).
Other Issues:
Role of industry in technology development and how the National Institutes of Health (NIH) and other
Government entities can partner better with academia and industry to make opportunities a reality
Need for partnerships for use of public and private sectors funds to develop diagnostic, clinical, and
therapeutic tools and to develop the chemical biology to enhance the imaging field
Need for systems biology individuals to work with technological companies to come up with ways of
assaying newly developing organ-specific proteins.
Overlap:
 With WG 1 Overview
 With WG 4 Cancers
 With WG 7 Oropharynx & Esophagus
 With WG 5 IBD
 GI bleeding: Bleeding is a sign of many different diseases, not a disease entity in itself. WG
13 should address novel technologies to diagnose the site and cause of GI bleeding. This
could include capsule endoscopy or other imaging technologies. Several of the chapters, such
as cancer, stomach, or colon, will include discussions of some of the most important
problems such as ulcers and vascular disease. See WG 8 “Overlap” section.
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