Transcript Probiotics and Various States of Diarrhea

Probiotics and Various States of
Diarrhea
By Lindsay Clapp-Hansen
Medical Nutrition Therapy
November 25, 2002
Probiotics
• Microbes found in the food supply that
enhance human health.
• Criteria: bacteria of human origin, able to
adhere to the intestinal mucosa, have
potential to colonize in the GI tract, can
produce antimicrobial substances, stable
against bile, HCl, and other acids, enzymes,
and oxygen, and determined to be safe and
effective.
Altered Disease States
Probiotics have been
thought to improve or
ameliorate a plethora
of states, the most
commonly reported
upon are:
• Various states of diarrhea
• Inflammatory Bowel
Disease
• H. Pylori Ulcers
• Urinary Tract Infections
• Vaginal Candida
Overgrowth
• Cancer of the
Gastrointestinal (GI) Tract
What has Scientifically Based
Research to Support the Claims?
After reviewing a majority of the research and
literature relative to probiotic use in humans, it
is clear that diarrhea is the condition most
beneficially treated by probiotic therapy. This
can include diarrhea associated with antibiotics,
travel, gastroenteritis, lactose intolerance, and
Inflammatory Bowel Disease. These areas were
reviewed.
Diarrhea Described
Diarrhea is frequent loose stools, along with
an excessive loss of fluid and electrolytes
(K & Na especially), abdominal cramping,
pain, and often presence of a fever.
It can be acute or chronic, and is secondary to
an underlying disease or condition or
pathogenic bacteria within the GI tract.
Types of Diarrhea
1.
2.
3.
4.
Osmotic—a result of poorly absorbed nutrients that enter
into the large intestine => a solute-related osmotic shift
Secretory—usually a result of bacterial or viral
infections, which causes excessive secretion of
electrolytes and water by the intestinal epithelium
Exudative– mucosal damage combined with a build up
of blood, mucous, and plasma proteins in the colon
Limited Contact Mucosal—caused by insufficient
blending of chyme and decreased exposure to the
intestinal epithelium
Antibiotic Associated Diarrhea
This is the most well studied area of probiotics, because
antibiotic associated diarrhea is evident in 20% of all
people on antibiotic therapy which provides a good
sample.
Cause- by the antibiotic therapy destroying the normal,
health-promoting gut flora as well as the pathogenic
bacteria.
Result- the healthy bacteria that usually protects the GALT
and the intestinal epithelium is not there, this enables
pathogenic bacteria to bind to the available receptors
How Probiotics Aide in
Decreased Antibiotic-Associated
Diarrhea:
• The probiotics promote increase production
of the synergistic bacteria, thus increasing
the quantity in the intestine & decreasing
the number of available receptor sites
Antibiotics & Probiotics Tested
• In 1989 the largest study on antibiotic-associated
diarrhea and probiotic intervention was completed.
This spurned more interest in the area.
• Prospective, double-blind, placebo-controlled trial
• N =180 hospital patients on antibiotics
• Experimental: Received S. boulardii in
conjunction with antibiotics.
• Results: There was a 13% decrease in overall
diarrhea symptoms when comparing the
experimental to the control.
1999 Quantified Study Released
A study using clear dosage levels was
published in 1999. It examined 119
children (2wks-12.8 yrs) on antibiotics. Half
were given a placebo and half a 2 * 10^10
colony forming units of Lactobacillus GG
twice a day. This was examined over a
three month period. During this time
careful stool frequency and consistency logs
were maintained by the parents of subjects.
Results
1. There was a 11% decrease of diarrhea in
the initial two weeks of probiotic therapy
when comparing the experimental group
to control.
2. By the third week, there was a 30%
decrease difference between the two
groups.
Confounds
• The study in 1989 was lacking in clearly
quantifiable values of probiotic dose.
• The study that was completed in 1999 was a break
through because there were standardized amounts
of probiotics given. However, the age range of
children does not enable a clear dose per weight
determination to be made.
• In all of the studies reviewed concerning
antibiotic-related diarrhea, there were one or more
of the following confounds: lack of specific detail
of amount and consistency of diarrhea and the
quantity and viability of the probiotic strains
administered. There leaves much to be researched.
Conclusion for Antibiotic
Associated Diarrhea
• There is a basis to believe that probiotics,
through competitive exclusion by the
enhancement of intestinal micro flora, are
able to lessen the frequency and duration of
diarrhea.
• More needs to be done in order to create
clinically applicable recommendations.
Traveler’s Diarrhea
• It has been estimated that 20-50% of all people
who travel are struck by diarrhea. The frequency
and duration is associated with the destination and
location of the traveler.
• Cause: it is presently unknown, but believed to be
due to a change in ingested microbial content and
stress. Pathogenic E. coli is usually protagonist.
• Result: unknown, however results in diarrhea.
Tested Probiotic Affect on
Traveler’s Diarrhea
• In 1993, a study was conducted that stated
47% of Americans traveling to Mexico were
able to avoid Traveler’s diarrhea when a
prophylactic dosage of Lactobacillus GG
was administered daily.
• This study was one of many, but is in
accordance with the majority of published
studies.
Traveler's Diarrhea Continued
• Other trials conducted showed a HUGE range
from >50% reduction with the supplementation of
probiotics to none at all.
• However, in all of the studies that compared
various ages, the outcome showed diminished
diarrhea within the elderly population when taking
a probiotic supplement. This shows that overall
GALT and immune function are related to how a
person will respond to microbes. This calls for
studies to be conducted on the elderly to determine
if probiotics could diminish nursing home GIrelated distress.
Infectious Diarrhea
• Infectious diarrhea can be induced by any
pathogenic virus or bacteria. Rotaviral diarrhea
will be covered here.
• Rotavirus attacks the GI tracts of newborns and
infants, and because of this it can be well isolated
and studied in relation to probiotic dosing.
• Rotavirus induces biphasic diarrhea, initially
osmotic and then secretory.
What Probiotics Do to Combat
Rotaviral Diarrhea
1. Stabilize the intestinal micro flora that’s been
altered by rotavirus (through reproduction
promotion)
2. The above results in reduced gut permeability,
which lowers the rate rotavirus can bind to the
GALT and cause gastroenteritis
3. Probiotics reduce the length of time rotavirus in
the intestine (due to competitive exclusion)
4. Probiotics increase the amount of IgA that the
body produces to fight infection.
Key Study: Rotavirus & Probiotics
• In 1997, a prospective, randomized, placebocontrolled trail was carried out to determine how
Lactobacillus reuteri affected rotavirus.
• Children between the ages of 6-36 months were
brought into the study post admit for rotaviralassociated diarrhea
• There were three groups: placebo, 1 dose of 10^10
cfu, and 1 dose of 10^7 cfu. The treatment was
given once daily for five days.
Results for Rotaviral Study
• Results showed that the duration of diarrhea in the
placebo group was 2.5 days in length as compared
to 1.9 days with the 10^7 dose, and 1.5 with the
10^10 dose.
• Additionally, stool cultures show that there was
significant probiotic colonization in the GI tract in
both test groups.
• This study, as well as others, shows that there is a
clear correlation between oral administration of a
probiotic strain and diminished rotaviral diarrhea.
• More must be researched to establish a clinically
meaningful therapy.
Lactose Intolerance
• Lactose intolerance presents in 70-100% of
adults worldwide.
• Probiotics function as a lactase isomer.
When probiotics deteriorate, they produce
B-D-galactosidase from the cell wall. This
is an isomer of lactase which then destroys
ingested lactose.
B-D-Galactosidase
• In order for the B-D-galactosidase to appear
in the GI tract, the probiotic must be
ingested in a viable state, and then
breakdown.
• This means that frozen yogurt and
pasteurized yogurt are not as effective as
fresh yogurt, because they do not produce
the B-D-Galactosidase.
Yogurt Conundrum
• So why is pasteurized yogurt tolerated?
• One study states that is it the decreased intestinal
transit time, which means that the lactose spends
less time as an undigested molecule within the
large intestine. If the lactase were to spend a
longer period of time in the large intestine,
fermentation and osmotic diarrhea would result.
• Other studies state that pasteurized yogurt causes a
delay in gastric emptying and orocecal transit
time, because the probiotics and organic acids they
produce result in a lower osmotic load.
So now what?
• There must be more research on how non-viable
(aka pasteurized) probiotics alter the lactose
intolerants GI tract that makes the person able to
consume lactose-containing yogurt.
• Over and over again the B-D-galactosidase has been
seen to break down lactose, so non-heat treated
yogurt is acceptable.
• Overall, the viable probiotics have been seen to have
a positive effect on lactose intolerant consumption of
dairy. Additionally, there is some manner in which
non-viable microbes are aiding in the acceptability
of lactose in the intolerant individual.
Inflammatory Bowel Syndrome
• IBD includes both Crohn’s and ulcerative
colitis. The cause of these disease states are
unknown, but it is believed to be due to
genetics and immunlogic deficiencies.
These disease states present when there is
an imbalance in the gut micro flora.
• The current method of treating IDB flare
ups is with antibiotics.
• In 1997, a double-blind study was conducted that
examined a probiotic (non-pathogenic E. coli) and
an antibiotic (mesalazine).
• The study included 120 adults, with inactive
colitis. They were divided into the two test
groups. Over a three moth period, they were asked
to assess the frequency, intensity, and an overall
health assessment.
• Results: The results were not clinically
significant, the E. coli group had a 16% rate of
controlled flare up, where as the mesalazine had
an 11% rate.
Not Clinically Significant, but Still
Significant
• Although the 11% vs. 16% is not clinically different,
this shows that the probiotic was nearly as effective
as the antibiotic.
• Because IBD patients are immunosuppressed, the
reduction in antibiotic associated diarrhea would
improve the overall quality of life.
• By taking the probiotic therapy instead of the
antibiotic, there would be commensal bacterial
growth within the intestine, which would act as a
barrier against ingested pathogens and promote the
production of IgA immune response within the gut
IBD & Probiotics
• Although it seems that probiotics could at some
point be an alternative therapy for IBD, it is not
possible now, because standardized doses must be
determined. More research must be done to
determine if antibiotic-associated diarrhea in the
IBD patient can be significantly reduced.
• After reviewing the literature, the consensus is that
probiotics as a supplement are not altering IBD
significantly.
Probiotic Research Overall
• The studies that have been completed are limiting
because there are not standardized amounts, there
is a large variation in the strain used for
experimentation, the viability of the microbes are
not tested pre-experimentation.
• More must be done so that this potentially
beneficial supplement can be used in practice
Conclusion
• Probiotics are able to decrease the
length/incidence of antibiotic-induced diarrhea
through competitive exclusion.
• Probiotics were seen to decrease the severity and
length of traveler’s diarrhea, especially among the
elderly.
• Rotaviral-associated diarrhea cases were
positively altered when oral probiotics were
administered.
Conclusion
• Lactose intolerance and probiotics is still
controversial. Viable probiotics clearly have a
positive function. Pasteurized probiotics are an
unknown area at present.
• IBD is likely not significantly altered through
probiotic supplementation, however probiotics
could potentially be used instead of antibiotics to
control flare-ups, which may decrease the
incidence of antibiotic-associated diarrhea.
Areas of Research
• The correlation between probiotic therapy
and increased production of IgA.
• Determining the best strains and the
quantities that are needed to support
intestinal health promotion.
• Research that has minimal confounds so
that it will be honored by the scientific
community.