Expert Review of Gastroenterology & Hepatology

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Helicobacter pylori: beneficial for most?

Stephanie Y Owyang, Jay Luther & John Y Kao

To cite this article: Stephanie Y Owyang, Jay Luther & John Y Kao (2011) Helicobacter�pylori:
beneficial for most?, Expert Review of Gastroenterology & Hepatology, 5:6, 649-651, DOI: 10.1586/
egh.11.69

To link to this article: https://doi.org/10.1586/egh.11.69

Published online: 10 Jan 2014.

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Helicobacter pylori: beneficial for most?
Expert Rev. Gastroenterol. Hepatol. 5(6), 649–651 (2011)
Stephanie Y
Owyang
University of Michigan Health
System, 6520A MSRB 1,
SPC 5682, 1150 W Medical
Center Drive, Ann Arbor,
MI 48109, USA
Jay Luther
University of Michigan Health
System, 6520A MSRB 1,
SPC 5682, 1150 W Medical
Center Drive, Ann Arbor,
MI 48109, USA
John Y Kao
Author for correspondence:
University of Michigan Health
System, 6520A MSRB 1,
SPC 5682, 1150 W Medical
Center Drive, Ann Arbor,
MI 48109, USA
jykao@med.umich.edu
www.expert-reviews.com 10.1586/EGH.11.69
“…Helicobacter pylori may also have a protective effect against
the development of autoimmune disease.”
Humans have been infected with Helico­
bacter pylori since they left Africa more
than 58,000 years ago, according to genetic
sequence analysis [1] . Estimates suggest that
half the world is infected with the bacteria,
with an especially high rate of infection in
Asia [2] . In 1984, Barry Marshall and Robin
Warren discovered that H. pylori was the
cause of peptic ulcers and gastritis [3] ; since
then, the way we think about and treat
peptic ulcer disease and gastric malignan-
cies has been completely revolutionized.
H. pylori is the first thing we think of and
search for before discussing additional diag-
noses. Two decades of work have gone into
developing effective vaccines for the bac-
teria, and since it affects half the world, a
global vaccination program to eradicate it
seems to make sense.
Main issue: is H. pylori good
or bad?
In 2007, an NIH workshop on H. pylori
research brought forward a panel of experts
to discuss directions for future research on
H. pylori and concluded that H. pylori is
harmful to a small subset of patients, but
that there is enough evidence to suggest
that it is also beneficial. Infection with
H. pylori is asymptomatic in approximately
85% of individuals, while 15% develop
symptomatic peptic ulcer disease, and less
than 1% go on to develop gastric cancer [4] .
Negative correlations with asthma  [5] ,
eczema [6] and gastrooesophageal reflux
disease [7] have been found, but the respon-
sible mechanism remains to be elucidated.
Keywords : DNA • Helicobacter pylori • inflammation • inflammatory bowel disease
© 2011 Expert Reviews Ltd
Editorial
These observations suggest that H. pylori
may also have a protective effect against the
development of autoimmune disease.
Negative assocciation with
inflammatory bowel disease
Epidemiological studies indicate that
inf lammatory bowel disease (IBD) is
more prevalent in areas with lower rates of
H. pylori colonization, such as the USA [8] .
On the other hand, there is a steady rise in
the incidence of IBD in H. pylori-endemic
regions that corresponds to the beginning
of anti-H. pylori therapy for peptic ulcer
disease [9] . These observations have led
to a number of studies investigating the
association between H.  pylori infection
and IBD.
“Most people count all
Helicobacter pylori strains as
‘bad’, but it is possible that some
strains are more harmless
than others.”
Our laboratory recently published a
meta-ana­lysis showing a negative corre-
lation with IBD: 27.1% of IBD patients
showed evidence of H.  pylori infection
compared with 40.9% patients in the
control group [10] . These data suggest that
there are protective benefits of H. pylori
infection against the development of IBD.
However, long-term studies investigating
the effect of eradication of H. pylori on the
development of IBD are warranted.
ISSN 1747-4124 649
 Editorial Owyang, Luther & Kao
Like the asthma and obesity studies, there existed no mecha-
nistic studies to explain this correlation. Commonly cited as the
explanation for this negative association is the hygiene hypoth-
esis: cleaner conditions early in life lead to a higher incidence of
autoimmune diseases later in life by suppressing natural develop-
ment of the immune system. H. pylori infection is more prevalent
in developing parts of the world with poor hygiene. Since poor
sanitary conditions are thought to play a role in the lower rates
of IBD in these parts of the world, H. pylori infection is widely
believed to be a marker of poor hygiene in one’s birthplace, and
not a direct contributor to protection against IBD.
“If we look at Helicobacter pylori as a good
bacterium with bad side effects … perhaps we can
gain something from this bug.”
Mechanisms
Helicobacter  pylori infection triggers a unique inflammatory
response in which the infection persists despite the activation and
recruitment of T and B lymphocytes, phagocytic cells and other
immune cell populations [11] . This suggests that H. pylori infec-
tion may induce immune tolerance, favoring its persistence in the
stomach. To investigate further the H. pylori–IBD connection, the
direct influence of H. pylori infection on the host immune system
needs to be elucidated. This cannot be performed in the clinical
setting given that environmental hygiene is a strong confound-
ing factor. Thus, we carried out this study in a mouse model of
H. pylori infection and experimental colitis. We first showed that
H. pylori infection can protect against Salmonella typhi-induced
experimental colitis  [12] . Higher IL-10 in the mesenteric lymph
nodes could explain the protective mechanism. We employed a
mouse model of H. pylori infection and showed that induction
of Tregs by H. pylori appears to be a major adaptation to evade
host immunity [13] . H. pylori alters the dendritic cell-polarized
Th17/Treg balance toward a Treg-biased response, resulting in
suboptimal Th17 response and failure to eradicate the offending
pathogen. This mechanism may also explain the negative correla-
tion that exists between H. pylori infection and the incidence of
IBD, a condition in which Th17 may play a pivotal role. Arnold
et al. provided more evidence that H. pylori infection enhances the
Treg response and thus limits the severity of asthma in a mouse
model [14] . In subsequent studies we further demonstrated that
H. pylori DNA decreases proinflammatory cytokine production by
dendritic cells and attenuates dextran sodium sulfate-induced coli-
tis in mice. We showed that H. pylori DNA, which has been found
in the colon and stool of infected patients [15,16] , has immunoregula-
tory properties [17] . H. pylori DNA suppresses type 1 interferon and
IL-12 production from mouse bone marrow-derived dendritic cells,
possibly owing to its high immunoregulatory sequence to immuno­
stimulatory sequence ratio. This may explain why the systemic
levels of type 1 interferon were found to be lower in H. pylori-
colonized patients than noncolonized controls [17] . We also showed
that the administration of isolated H. pylori DNA significantly
ameliorated the severity of experimental colitis in mice.
650
Clinical implications
Clinical studies clearly demonstrate that eradication of H. pylori
infection significantly reduces the incidence of peptic ulcer disease
and its complications. This supports the recommendation by the
NIH that H. pylori is harmful to a small subset of patients and
should be appropriately treated. However, because of immune
tolerance conferred by H. pylori infection, its elimination from
the body in asymptomatic patients may not be a good idea. Up to
50% of patients may experience mild side effects associated with
antibiotic treatment [18] . Furthermore, treatment fails in approxi-
mately 25% of patients [19] , so widespread use of antibiotics may
result in future antibiotic-resistant strains. Therefore, we recom-
mend that only symptomatic patients or asymptomatic family
members of gastric cancer patients should be tested and treated.
Unless treatment is considered, if the result is positive, physicians
should not test the patient for H. pylori.
Research implications
We know that H. pylori causes ulcers, but do all strains of H. pylori
cause ulcers? Most people count all H. pylori strains as ‘bad’,
but it is possible that some strains are more harmless than oth-
ers. More research needs to be conducted on differences between
strains before we blacklist all of them. In addition, we know that
Asian populations have an especially high incidence of gastric
cancer, but no convincing theory exists as to why. If we can
understand why some people experience symptoms while others
remain asymptomatic, then we may be more efficient at treating
the infection and even providing H. pylori-based treatments for
chronic inflammatory conditions.
Conclusion
It is good to recognize that H. pylori causes serious symptoms
in 15% of those infected, but it is also essential to consider the
remaining 85% of H. pylori carriers: quite possibly, the bacterium
is protecting these people from chronic inflammation, a burgeon-
ing problem in today’s steadily advancing society. Before eradicat-
ing the bacteria, the beneficial effects of H. pylori and differences
between strains need to be examined more thoroughly to make
sure we are not eliminating a potential, albeit hidden, ally that has
lived with us for more than 58,000 years. By treating those who
are unaffected, we could be unwittingly breeding susceptibility
to a host of serious chronic inflammatory problems; however, by
properly harnessing H. pylori’s veiled benefits (i.e., its DNA), we
may be able to obtain all the advantages without any of the com-
plications. If we look at H. pylori as a good bacterium with bad
side effects as opposed to a bad bacterium with good side effects,
perhaps we can gain something from this bug.
Financial & competing interests disclosure
John Y Kao is a consultant for Otsuka America Pharmaceutical, Inc. The
authors have no other relevant affiliations or financial involvement with
any organization or entity with a financial interest in or financial conflict
with the subject matter or materials discussed in the manuscript apart from
those disclosed.
No writing assistance was utilized in the production of this manuscript.
Expert Rev. Gastroenterol. Hepatol. 5(6), (2011)

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