Since the discovery of Helicobacter pylori (H. pylori) in 1982 as a major cause of gastric ulcer disease, several other H. subspecies have been found to cause variety of gastrointestinal and hepatic diseases in animals and humans.
That possible involvement of Helicobacter species in Crohn's disease is not just a pure speculation, testifies the following meeting:
Helicobacter pylori meets inflammatory bowel disease
-International workshop on mucosal inflammation and cytokines-
July 31st to August 1st, 1998, Kobe, Japan
Professor Takashi Shimoyama from Hyogo College of Medicine recently
convened the above meeting in Kobe, Japan. The meeting planned by
Professor Shimoyama and Dr Fukuda
in conjunction with Adrian Lee and Tony Axon, was the first meeting
to look at the interesting
parallels between Helicobacter infection and Inflammatory Bowel Disease.
The invited international participants were: Daniel Podolsky USA, Tony
Axon UK, Jean Crabtree UK, Alan Levine USA, Jim Fox USA, John Cummings
UK, Richard Bicks USA, Michael Kamm UK, Adrian Lee Australia, Roy Pounder
UK, Colm OíMorain Ireland. The meeting was a great success and will
eventually be published in book form.
Similarity of H. hepaticus infection in mice and Crohn's disease
with liver involvement
H. hepaticus causes chronic liver disease associated with IBD
in mice, H. canis causes hepatitis in dogs, while undetermined H. subspecies
were isolated from human patients with gallbladder
disease
and primates with chronic colitis. In humans,
IBD is associated in roughly 10-30% of the cases with abnormal
liver tests, and in 10% with serious complication of Primary Sclerosing
Cholangitis. This similarity between animal and human disease may prompt
us to speculate involvement of Helicobacter species in Crohn's disease
cases associated with liver disease (it is already accepted today that
several pathogens may be involved in different cases and presentations
of Crohn's disease, allowing for H. species to be involved in just this
subgroup of patients).
Response to antibiotic Metronidazole in different Helicobacter infections
and Crohn's
Earlier studies in Crohn's disease transmission have shown that it
is possible to induce chronic intestinal inflammation in laboratory
animals by inoculating them with intestinal isolates from Crohn's patients
while this was not happening when the isolates were from UC or other human
GI disease patients. Pointing even more in the infectious direction is
a study where induction was prevented by adding an antibiotic to the isolate
prior to inoculation. Finally, use of antibiotics
in active phase of Crohn's disease has shown that remission can be
induced with combination regimen based on Metronidazole which is also the
base of combination regimen used against H. pylori and H. hepaticus.
INFLAMMATORY BOWEL DISEASE: AN IMMUNITY-MEDIATED
CONDITION TRIGGERED BY BACTERIAL INFECTION WITH HELICOBACTER HEPATICUS.
Cahill RJ; Foltz CJ; Fox JG; Dangler CA; Powrie F; Schauer DB, Division
of Comparative Medicine, Massachusetts Institute of Technology, Cambridge
03129, USA. Infect Immun, 1997 Aug, 65:8, 3126-31
Inflammatory bowel disease (IBD) is thought to result from either an
abnormal immunological response to enteric flora or a normal immunological
response to a specific pathogen. No study to date has combined both factors.
The present studies were carried out with an immunologically manipulated
mouse model of IBD. Mice homozygous for the severe combined immunodeficiency
(scid) mutation develop IBD with adoptive transfer of CD4+ T cells expressing
high levels of CD45RB (CD45RB(high) CD4+ T cells). These mice do not develop
IBD in germfree conditions, implicating undefined intestinal flora in the
pathogenesis of lesions. In controlled duplicate studies, the influence
of a single murine pathogen, Helicobacter hepaticus, in combination with
the abnormal immunological response on the development of IBD was assessed.
The combination of H. hepaticus infection and CD45RB(high) CD4+ T-cell
reconstitution resulted in severe disease expression similar to that observed
in human IBD. This study demonstrates that IBD develops in mice as a consequence
of an abnormal immune response in the presence of a single murine pathogen,
H. hepaticus. The interaction of host immunity and a single pathogen in
this murine system provides a novel model of human IBD, an immunity-mediated
condition triggered by bacterial infection.
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HEPATIC HELICOBACTER SPECIES IDENTIFIED IN
BILE AND GALLBLADDER TISSUE FROM CHILEANS WITH CHRONIC CHOLECYSTITIS.
Fox JG; Dewhirst FE; Shen Z; Feng Y; Taylor NS; Paster BJ; Ericson
RL; Lau CN; Correa P; Araya JC; Roa I, Division of Comparative Medicine,
Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307,
USA. jgfox@mit.edu Gastroenterology, 1998 Apr, 114:4, 755-63
BACKGROUND & AIMS: Cancer of the gallbladder is the number one cause
of cancer mortality in Chilean women. Incidence rates for this tumor vary
widely on a worldwide basis, being approximately 30 times higher in high-risk
than in low-risk populations, suggesting that environmental factors such
as infectious microorganisms, carcinogens, and nutrition play a role in
its pathogenesis. Because several Helicobacter sp. colonize the livers
of animals and induce hepatitis, the aim of this study was to determine
whether Helicobacter infection was associated with cholecystitis in humans.
METHODS: Bile or resected gallbladder tissue from 46 Chileans with chronic
cholecystitis undergoing cholecystectomy were cultured for Helicobacter
sp. and subjected to polymerase chain reaction (PCR) analysis using Helicobacter-specific
16S ribosomal RNA primers. RESULTS: Recovery of Helicobacter sp. from frozen
specimens was unsuccessful. However, by PCR analysis, 13 of 23 bile samples
and 9 of 23 gallbladder tissues were positive for Helicobacter. Eight of
the Helicobacter-specific PCR amplicons were sequenced and subjected to
phylogenetic analysis. Five sequences represented strains of H. bilis,
two strains of “Flexispira rappini” (ATCC 49317), and one strain of H.
pullorum. CONCLUSIONS: These data support an association of bile-resistant
Helicobacter sp. with gallbladder disease. Further studies are needed to
ascertain whether similar Helicobacter sp. play a causative role in the
development of gallbladder cancer.
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NOVEL INTESTINAL HELICOBACTER SPECIES ISOLATED
FROM COTTON-TOP TAMARINS (SAGUINUS OEDIPUS) WITH CHRONIC COLITIS.
Saunders KE, Shen Z, Dewhirst FE, Paster BJ, Dangler CA, Fox JG
Division of Comparative Medicine, Massachusetts Institute of Technology,
Cambridge, Massachusetts 02139, USA. Clin Microbiol 1999 Jan;37(1):146-51
A disease similar to ulcerative colitis in humans has been identified
in cotton-top tamarins (CTTs) in
captivity. The clinical signs include weight loss, diarrhea, and rectal
bleeding with the pathological
features and biochemical abnormalities of ulcerative colitis. Approximately
25 to 40% of these animals develop colon cancer after 2 to 5 years of captivity.
An infectious etiology has been proposed; however, no microbial agent to
date has been identified. Helicobacter spp. have been associated with enterocolitis
and inflammatory bowel disease (IBD) in humans and animals. Infection with
Helicobacter pylori or Helicobacter mustelae is associated with an increased
risk of gastric
adenocarcinoma and lymphoma of the mucosa-associated lymphoid tissue.
Helicobacter hepaticus
causes hepatitis, hepatic adenomas, and hepatocellular carcinomas in
susceptible strains of mice. The
aim of this study was to assess a colony of CTTs with a high incidence
of IBD and colon cancer for
the presence of colonic Helicobacter spp. A fusiform, gram-negative
bacterium with bipolar flagella
and periplasmic fibers was isolated from the feces of CTTs. The bacterium
grew under microaerobic
conditions at 37 and 42 degreesC but not at 25 degreesC, did not hydrolyze
urea, was positive for
catalase and oxidase, did not reduce nitrate to nitrite, did not hydrolyze
indoxyl acetate or alkaline
phosphatase, and was resistant to nalidixic acid, cephalothin, and
trimethoprim-sulfamethoxazole. On
the basis of 16S rRNA gene sequence analysis, the organism was classified
as a novel Helicobacter
species. This is the first Helicobacter isolated from CTTs. Further
studies are needed to elucidate the
role of this novel Helicobacter sp. in the pathogenesis of ulcerative
colitis and colonic adenocarcinoma in CTTs.
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HEPATOBILIARY AND COEXISTING PANCREATIC DUCT ABNORMALITIES
IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE.
Heikius B; Niemelä S; Lehtola J; Karttunen T; Lähde S; Dept.
of Internal Medicine, University Hospital of Oulu, Finland.
Scand J Gastroenterol, 1997 Feb, 32:2, 153-61
BACKGROUND: We performed a cross-sectional study to evaluate the prevalence
of hepatobiliary disease in unselected patients with inflammatory bowel
disease (IBD), to estimate the frequency of coexisting cholangiographic
and pancreatographic duct abnormalities, and to correlate the findings
with clinical, endoscopic, and histologic variables. METHODS: We
screened 237 IBD patients for increased liver function values. Further,
hepatobiliary evaluation consisted of transabdominal ultrasonography, endoscopic
retrograde cholangiopancreatography (ERCP), and a liver biopsy. In addition,
we evaluated the ERCP findings of patients with abnormal pancreatic screening
tests (pancreatic enzymes or para-aminobenzoic acid excretion). RESULTS:
Laboratory signs of hepatobiliary disease were found in 37 (16%) of our
IBD patients. Abnormal liver test results were commoner in patients with
Crohn’s disease (CD) than in patients with ulcerative colitis (UC) (30.4%
versus 11.2%, P < 0.05), and a similar trend was observed in the frequency
of primary sclerosing cholangitis (PSC) in the respective groups of IBD
patients. When the ERCP findings were combined with liver histology, 26
(11% of the whole study group) patients with PSC were found, with small-duct
disease included. In 23 (10% of the whole study group) patients, definite
cholangiographic changes consistent with PSC were found. Eleven (48%) of
these showed coexisting pancreatic duct abnormalities. The prevalence of
coexisting cholangiographic and pancreatographic duct changes in the whole
study group was 4.6%. CONCLUSION: Hepatobiliary disease is at least
equally common in patients with UC and CD. Coexisting cholangiographic
and pancreatographic duct abnormalities in patients with IBD are relatively
frequent and are considered extraintestinal manifestations of IBD.
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