Living
Bacteria — The Body’s Natural Defense
By Victoria Shanta-Retelny, RD, LD
Today’s Dietitian
Vol. 7 No. 5 P. 44
It’s alive! And evidence is mounting that
probiotics can play a more therapeutic role in gut health.
At the microscopic level, the human body is colonized
by millions of bacteria all jockeying for position—some intent
on fostering disease and others inherently fending diseases off
by improving health and wellness. The probiotic concept suggests
that adding certain bacteria to our diets can encourage the beneficial
microbial activities in our bodies. The Food and Agriculture Organization
defines probiotics as “live microorganisms which when administered
in adequate amounts confer a health benefit on the host.”1
Numbers and bacterial population types vary among
the stomach, small intestine, and colon because different transit
times and secretions affect numbers and composition of microflora.
The most heavily colonized area of the human body, the large intestine,
has been found to have the highest degree of metabolic activity.2
At birth, the large gut microflora is being established
and teaming with strains such as Escherichia coli (E. coli). From
infancy, diet plays a major role in determining development of types
of bacterial species. Breast-fed vs. formula-fed infants show a
marked difference in the predominant microflora. The fecal flora
of breast-fed infants is so heavily dominated by the probiotic genus,
Bifidobacterium, that it is considered the “gold standard”
type of gut flora, which imparts excellent resistance to infection.2
On the other hand, in formula-fed infants, no one microbial group
predominates—rendering the system less able to fight infection.
In the human adult colon, research has shown that
bacteria play a huge role in health maintenance. The adult colon
is approximately 150 centimeters in length with a typical transit
time of 24 to 72 hours—enough time for large numbers of bacteria
to grow.3 The colon is a breeding ground for bacteria with roughly
100 grams of dietary residues from carbohydrates, proteins, amino
acids, and lipids entering it daily. Thus, ample growth substrate
is present for nourishing native colonic bacteria sources, such
as mucus secretions and epithelial cells. Ninety percent to 95%
of total cells in the body are thought to be large intestinal bacteria.3
It makes sense that gut bacteria affects health and disease as much
as it does.
According to Glenn Gibson, PhD, professor of food
microbiology at The University of Reading, United Kingdom, “Probiotics
prophylactically manage acute and chronic gut disorder; evidence
is accumulating for a more therapeutic role, also. Higher levels
of these beneficial organisms can thereby reduce the activities
of more problematic pathogens—either present in the gut or
transmitted in food and/or water.”
Disease Proliferation and Health
Maintenance
The gut is the principal immune organ of the body with more than
400 cultivable species.4 While a majority of the indigenous flora
are benign or exhibit health-promoting properties, some possess
the potential to cause disease. Experts contend that bifidobacteria
and lactobacilli are associated with health and commonly used as
probiotics, while clostridia are considered detrimental to health.4
Consumption of specific strains of probiotics is associated with
a range of health benefits, such as improvement of diarrheal conditions
(acute infantile diarrhea, antibiotic-associated diarrhea, nosocomial
infections), lactose intolerance, systemic infections, allergies,
cancer, hypercholesterolemia, inflammatory bowel disease, and immunomodulation.4,5
Probiotics and Prebiotics
If probiotics are live microbes that are beneficial to health, then
what are prebiotics? In 1995, Gibson and his Belgian colleague Professor
Marcel Roberfroid first coined the term prebiotic. Prebiotics are
dietary carbohydrates that are selectively metabolized (carbohydrates
do not have metabolism) in the colon and serve to increase numbers
of bacteria considered desirable.6 In other words, says Gibson,
“a prebiotic is a dietary ingredient that enters the gut and
fortifies components of the indigenous flora seen as beneficial.”
Global Historical Perspective
Probiotic use in humans has a long history with the first reported
intakes being the ingestion of soured milks by Nomads more than
2,000 years ago.2 More than a century ago, Ellie Metchnikoff, known
as the pioneer of probiotics, observed that the complex microbial
population of the colon was adversely affecting the host through
“autointoxication.” The true probiotics discovery came
when Metchnikoff linked increased longevity in Bulgarians who regularly
consumed fermented milk, specifically containing lactic acid bacteria.
As the story goes, he abandoned his practice of surgical removal
of the colon and began modifying the colonic microflora with the
ingestion of live active yogurt or soured milk cultures.
The awareness and acceptance of beneficial bacteria
differs globally. The U.S. thinking is less progressive in this
area. “There is little understanding of ‘good’
cultures as we are more focused on bacteria as a pathogen,”
says Mary Ellen Sanders, PhD, president of the International Scientific
Association for Probiotics and Prebiotics and a consultant microbiologist
with Dairy and Food Culture Technologies. Asia and the European
Union throw big money at research in the probiotics/prebiotics arena.
“Europeans like fermented dairy products as reflected in higher
consumption in Northern Europe; Asian people don’t mind talking
about bowel health as they are much more intestinal and GI [gastrointestinal]
health-oriented,” she explains.
Active Cultures
When we think of probiotics, we typically think of the “active
cultures” in yogurt, although the types of bacteria go far
beyond the traditional yogurt cultures, Lactobacillus bulgaricus
and Streptococcus thermophilus. “The actual strain of bacteria
is important,” Sanders says. Some yogurt manufacturers disclose
the exact strain of bacteria used in the product, but most do not.
As Sanders points out, “Most dairy products containing probiotics
in the U.S. do not provide information to consumers on product-
or strain-specific efficacy research, dose, or even strains used
in the product.” One exception is DanActive, which is formulated
with a strain of Lactobacillus casei (L. casei) that has been evaluated
in clinical trials. Information on efficacy and dose for this product
is available at http://danactive.com. Sanders is a big proponent
of manufacturers providing information about the specific bacterial
strains used. “Different strains of even the same species
of bacteria may have different functions. Think of how different
a Chihuahua and German Shepherd are even though they are of the
same species,” she says.
Approximately 80% of the yogurt manufactured in
the United States contains Lactobacillus acidophilus added as a
probiotic.7 Bifidobacterium strains are also added to some yogurts.
The National Yogurt Association established a “Live Active
Culture” seal that can be used on the label of any yogurt
containing 108 viable lactic acid bacteria per gram at the time
of manufacture. However, this seal does not tell the consumer anything
about the level of probiotic bacteria added in addition to the yogurt
starter cultures.7 Other dairy products that contain probiotic bacteria
are culture-added fluid milks (eg, Sweet Acidophilus milk), some
cottage cheeses, a few cheeses, and some nondairy milk-type beverages.
Outside the United States, probiotic-containing food products include
cheese, toddler formula, and juices.7 The FDA is open to allowing
Streptococcus thermophilus and Bifidobacterium lactis in infant
formula for those over 4 months of age, but no such products are
yet on the market in the United States.
Functional Foods
In an effort to maintain healthy microflora, “functional”
foods contain probiotics and prebiotics in their ingredient profiles.
“Current marketing strategies target improved resistance to
infections such as irritable bowel syndrome, chronic gut disorder
such as inflammatory bowel disease and colon cancer, lactose intolerance,
coronary heart disease, recurrent vaginal thrush, skin problems,
food allergy, and mineral bioavailability,” explains Gibson.
“The success rates are variable because in order for probiotics
to benefit the host, they must have robust survival properties in
the gut, which is their first point of contact.”
The role functional foods might play in enhancing
human health is continuing to develop.8 There is currently no legal
definition of functional food in the United States; however, it
is frequently defined as foods that offer health benefits beyond
basic nutrition.8 Regardless of the lack of definitive clarity,
the topic of functional foods still holds American consumer interest.
The fifth annual “Food for Thought” survey by the International
Food Information Council revealed that 11% of all 2003 food news
topics covered functional foods.9
Embedded in any discussion of diet and health is
the concept of functional foods; however, the question of optimal
health is complicated by matters such as food composition patterns,
food synergy, interactions among food components, and the impact
of sustaining dietary patterns over the long term.8 One of the most
paramount considerations when educating the public on healthy food
choices is the unique genetic and physiological status of the individual.
A recommended dietary intervention must be based on how the individual
will respond.
Probiotics are widely recognized as functional ingredients
for both food enhancement qualities and/or as a basis for dietary
supplements. “I am more inclined to recommend functional foods
containing probiotics than supplements. The advantage of food sources
of probiotics is that they supply a combination of other nutrients
besides probiotics and may also help ensure the survival of the
probiotics in the intestinal tract,” explains Jeannie Moloo,
PhD, RD, a registered dietitian in private practice in Roseville,
Calif., and spokesperson for the American Dietetic Association.
There is more concern with supplements as you don’t
always know what you are getting. “I may suggest incorporating
into my client’s diet yogurts and kefir for their Lactobacillus
content. As for probiotic supplements, considerable differences
exist in composition, doses, and biologic activity between various
commercial preparations. In addition, costs to the patient may be
considerable since no preparation is FDA-approved and hence are
not reimbursed by insurers,” says Moloo.
The lactic acid excreting bacteria, such as lactobacilli
(eg, L. casei, L. acidophilus, L. fermentum, L. johnsonii, L. plantarum,
L. rhamnosus) or bifidobacteria (eg, B. longum, B. infantis, B.
bifidum) are the most widely used in functional foods and supplements.
Lactococci, streptococci, and yeasts such as Saccharomyces are also
used in probiotic products. “Probiotics differ in their ability
to resist gastric acid and bile acids and colonize in the intestinal
tract,” emphasizes Moloo.
Regulation of Probiotics and
Prebiotics
Successful and responsible introduction of probiotic and prebiotic
products into the worldwide marketplace requires labeling for health
benefits that meet consumer needs, adhere to regulatory standards,
and do not overextend scientific evidence.10 The professional conundrum
for those in the probiotic and prebiotic fields is proper substantiation
of efficacy needed to support health claims. Tremendous progress
has been made over the past decade documenting in well-designed
human studies the impact of probiotics on health.11 “The whole
field has exploded in the last 10 years,” Sanders explains.
Global efforts on the part of national regulatory agencies have
improved with respect to ensuring that product claims are truthful
and not misleading.
The science of determining predictors for efficacy
on human health is plagued with barriers. One large barrier to the
development of biomarkers relevant to the study of probiotics is
that the composition of the human gut flora is not fully characterized
and the significance of the presence, absence, or certain levels
of different genera, species, or strains of bacteria is not understood.10
Efficacy Evidence
Efficacy evidence varies from in vitro studies to animal models
to human case studies to the cornerstone of efficacy substantiation,
human randomized control trials. Just as in any other field, in
the probiotic and prebiotic world, the type of evidence matters
when determining efficacy on human health. Sanders’ article
in the European Journal of Nutrition highlights the pros and cons
of the following types of efficacy evidence:
• In vitro evidence has been found to be a
good first step in screening for probiotic safety and efficacy;
these studies are useful for providing important strain characterization
data. However, they have been found to be too simplistic and fail
to successfully mimic the conditions in the human organism.
• Animal model systems are important in gaining
approval for human studies by institutional review boards, as only
limited tests can be preformed in humans for ethical reasons. The
weakness of this mode of evidence gathering is that there are anatomical,
metabolic, and physiological differences between animals and humans.
They work as indicators of efficacy, but usually the doses used
in animal studies are not realistic for humans.
• Human case studies are very general as they
only take into account a single case. Results are likely to be biased
toward specific cases and do not provide sufficient evidence of
probiotic or prebiotic efficacy. They can raise public awareness
but should always be confirmed by well-designed, randomized, double-blind,
controlled trials.
• Well-designed, randomized, double-blind,
controlled human trials are the most effective ways to evaluate
functional foods. The trick is defining the active ingredients of
a product as it is sold in the marketplace because with time and
storage conditions, the product may undergo changes. The other considerations
are developing an appropriate placebo, adequately randomizing the
study, and being able to reproduce the study at different sites.
Long-term intervention studies are needed to observe the improvement
of wellness. Most probiotic and prebiotic studies are short-term
(less than 12-week) studies.10
Education
When educating patients about the efficacy of probiotics for their
specific conditions, there are some important considerations. “We
need to keep in mind that most clinical studies have been small,
making it difficult to draw conclusions regarding the efficacy of
probiotics,” cautions Moloo. “Not all probiotics are
alike and as a result, clinical benefits will differ among people.
Probiotics differ in their ability to resist gastric acid and bile
acids and colonize in the intestinal tract. What we know to date
is that there are three general methods by which intestinal microflora
can be altered: by taking antibiotics, prebiotics, or probiotics.”
Adequate Dosing for Health Benefits
“Typical doses of probiotics range from 1 to 10 billion colony-forming
units a few times a week,” states Moloo. To maintain their
effect on the GI system, essentially all studies documenting efficacy
for probiotics use daily administration. Since probiotics are transient
and do not necessarily adhere but interact with epithelial cells,
a daily dosage is typically required.
“To me, there is no upper dose. Since the
gut is so hugely competitive and there are millions of bacteria
there already, the more the better as far as probiotics go,”
advises Gibson. As far as prebiotics, the dosage ranges from 5 to
15 grams per day, with 8 grams per day on average.
Future of Beneficial Bacteria
The future will see the development of new, well-characterized,
scientifically proven probiotic strains with specific health benefits.8
It is forecasted that probiotics will do more than the clinically
proven benefits. These good bacteria will possibly serve to prevent
and manage overexpressed immune function and improve efficacy of
vaccines in population groups with less than optimal immune function
(eg, infants, older adults, immunocompromised).8 Experts contend
that the future of probiotics warrants more research to confirm
physiological benefits, identify mechanisms of action, and develop
the technology to improve delivery of products that are attractive
to the consumer.
— Victoria Shanta-Retelny, RD, LD, is a
practicing dietitian at Northwestern Memorial Wellness Institute
in Chicago, a freelance food and nutrition writer, and a culinary
spokesperson.
References
1. Health and nutritional properties of probiotics in food including
powder milk with live lactic acid bacteria. Report of a joint FAO/WHO
expert consultation on evaluation of health and nutritional properties
of probiotics in food including powder milk with live lactic acid
bacteria. Cordoba, Argentina, Food and Agricultural Organization
(FAO). October 1-4, 2001.
2. Gibson GR. Bacteria for dinner: The rise of probiotics.
School of Food Biosciences, The University of Reading, UK.
3. Gibson GR, Rastall RA. Which bacteria should
we be feeding when we eat dinner: How and why? School of Food Biosciences,
The University of Reading, UK.
4. Gill HS, Guarner F. Probiotics and human health:
A clinical perspective. Postgrad Med J. 2004;80:516-526.
5. Teitelbaum JE, Walker WA. Nutritional impact
of pre- and probiotics as protective gastrointestinal organisms.
Annu Rev Nutr. 2002;22:107-138.
6. Gibson GR, Fuller R. Aspects of in vitro and
in vivo research approaches directed toward identifying probiotics
and prebiotics for human use. Journal of Nutrition.
2000;130:391S-395S.
7. Sanders ME. Probiotics: Considerations for human
health. Nutr Rev. 2003;3(61):91-99.
8. Sander ME, Heimbach JT. Functional foods in the
USA: Emphasis on probiotic foods. Food and Science Technology
Bulletin. 2004;8:1-10.
9. International Food Information Council. 2003.
Food for thought V. Reporting of diet, nutrition, and food safety
1995-2003. Available at: http://www.ific.org/research/upload/FFTVFullReport.pdf.
10. Sanders ME, et al. Weight of evidence needed
to substantiate a health effect for probiotics and prebiotics. Eur
J Nutr. 2004;1-8.
11. Reid G, Sanders ME, Gaskins HR, et al. New scientific
paradigms for probiotics and prebiotics. J Clin Gastroenterol.
2003;37(2):105-118.
Examples of Microorganisms Used as Probiotics
• Lactobacillus (casei, acidophilus, plantarum, fermentum,
etc)
• Bifidobacterium (longum, lactis, infantis,
etc)
• Gram-positive cocci (eg, lactococci, streptococci)
• Bacillius
• E. coli
• Yeasts (eg, Saccharomyces)
— Source: Gibson GR. Bacteria for dinner:
The rise of probiotics. School of Food Biosciences, The University
of Reading, UK.
Gut Flora Facts
• The human gut contains 10 times more bacteria (1,014) than
eukaryotic cells in the entire human body.
• The total number of genes of the gut flora
is estimated to be 50 to 100 times the size of the human genome.
• The metabolic activity of the intestinal
flora is considered to be equal to the liver.
— Source: Gill HS, Guarner F. Probiotics
and human health: A clinical perspective. Postgrad Med J. 2004;80:517.
For More Information on Probiotics
• www.isapp.net
An international scientific association dedicated to probiotic and
prebiotic research
• www.usprobiotics.org
A comprehensive, up-to-date resource on activities, research, and
new developments in the area of probiotics
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