PROBIOTICS

Probiotics were defined by a group of experts convened by the Food and Agriculture Organization of the United Nations (FAO) as “live microorganisms administered in adequate amounts which confer a beneficial health effect on the host”.

Most probiotics are bacteria, which are small, single-celled organisms. Bacteria are categorized by scientists with genus, species and strain names. For example, for the probiotic bacterium, Lactobacillus rhamnosus GG, the genus is Lactobacillus, the species is rhamnosus and the strain is GG.

What Makes a Probiotic?

The requirements for a microbe to be considered a probiotic are simple. The microbe must be alive when administered, must be documented to have a health benefit and must be administered at levels shown to confer the benefit. A report on “Guidelines for the Evaluation of Probiotics in Food” considered more fully what minimum assessments a probiotic must undergo. The findings were:

Probiotic should be identified at the genus, species and strain level, using appropriate molecular and physiological techniques.
The strain should be deposited in an internationally recognized culture collection so that scientists are able to replicate published research on the strain and to serve as a reference strain.
Appropriate in vitro and animal assessments must be conducted to better understand the physiological attributes of the strain. However, the choice of what assessments are used should be based on assessments that are relevant to the probiotic function in the target host. Care must be taken to not overextend conclusions from in vitro and animal tests that have not been validated and shown to have relevance in the target host.
Before use, the safety of the microbe must be fully considered.
Properly controlled studies must be conducted which document a health benefit in the target host.
Ability to keep the probiotic alive at required levels in the final product through the end of shelf life.

Those with some familiarity with this field may notice that this list of requirements does not include attributes such as ability to adhere to intestinal cells, resistance to bile and acid, production of bacteriocins, antipathogenic activity, human origin, survival through intestinal transit, among others. This is because the array of potential health targets, hosts, and delivery methods are so diverse that any characteristics beyond those listed above are important for only a subset of probiotics, or because it is not clear if these assessments are truly predictive of in vivo functionality.

For example, sometimes it is claimed that probiotics must survive intestinal transit to be effective. Although there is little doubt that the ability of probiotics to grow and metabolize as they transit the intestinal tract can contribute to health benefits, there are also cases where this may not be necessary. In one case, preliminary research suggests that some probiotics may reduce the levels of Streptococcus mutans, the cause of dental caries, in the oral microbial community. A health benefit of this type would not require that the probiotic survive through the intestine.

At a minimum, probiotic products should be safe, effective, and should maintain their effectiveness and potency through the end of product shelf life. This requires a responsible approach both by the producer and the consumer. The producer must identify strains and conditions of storage that will assure consumers that the probiotic will stay alive at efficacious levels through the end of shelf life. The consumer must store and use the product according to manufacturers’ instructions.

Role of Probiotics in Health

For centuries, folklore suggested that fermented dairy products containing live active cultures are healthful. Recent controlled scientific investigation supports these traditional views, suggesting that probiotics can be a valuable part of a healthy diet. Probiotics are not essential for a healthy diet, but some compelling health benefits have been linked to some strains. These are discussed under “Health Effects of Probiotics.” In addition, the emergence of some new public health risks suggests an important role for effective probiotics in the mitigation of some illnesses. For example, the ability of probiotic bacteria to support the immune system could be important to the elderly or other people at risk for contracting common infectious diseases. (It is important that immune compromised individuals ask their doctor before taking any dietary supplement, including probiotics.)

Some infections, once thought self-limiting or readily treatable with antibiotics, are now recognized as more serious health threats. Bacterial vaginosis used to be considered just an annoyance. Now we know it is associated with low birth weight infants and increased risk of sexually transmitted diseases. New foodborne pathogens have emerged as prevalent and life threatening, including Shiga-like Escherichia coli strains. Multiple antibiotic resistances are a continual threat in the battle against once-treatable infections. And in non-industrialized nations, infections such as rotavirus claim the lives of hundreds of thousands of infants yearly. Prevention of infections before they occur is clearly the better alternative. Certain probiotics may be a safe, cost-effective approach that adds a barrier against or resistance to microbial infection.

How Probiotics Work

To understand how probiotics work, it is important to understand a little about the microbiology and physiology of the human gastrointestinal tract.

Human beings, like all animals, play host to many types and high numbers of microbes on our skin, in our mouths, in women’s vaginal tracts, and all the way through our gastrointestinal tract. In fact, it has been estimated that there are more microbes associated with the human body (about 10¹⁴, or 100,000,000,000,000 bacterial cells) than there are human cells in it (about 10¹³). In addition to this very large number of bacteria, a diverse variety of types of bacteria. It has been estimated that more than 1000 different species, or types, of bacteria make their homes on humans. In aggregate, these microbes are estimated to encode 100 times more metabolic genes than their human hosts. More importantly than the numbers and types of microbes that colonize our bodies is that they interact dynamically with each other and with our human cells. These colonizing microbes have been shown to have important roles in digestion, metabolism, vitamin synthesis, host cell development, immune system function, intestinal barrier function, defense against pathogens, and other activities that are critical to human health. The importance of this colonization to human health and development is reflected in the concept that humans are in effect “superorganisms”, composed of their own human genome and the combined microbes that colonize them. It is not possible to address human health without concomitantly considering the complement of colonizing microbes. Global research efforts are underway (see the International Human Microbiome Consortium) to study the role of the human microbiome in the maintenance of health and causation of disease and to use that knowledge to improve the ability to prevent and treat disease. This collaboration also aims to more fully characterize what microbes colonize humans and what functions those microbes carry out.

Taking this into consideration, it is not surprising that probiotics – by directly or indirectly influencing the populations or activities of our colonizing microbes – can impact human health.

Human Gastrointestinal System Review

The digestive process begins as soon as food enters the mouth. The process of chewing increases the surface area of food particles, making the food more susceptible to digestive enzymes, including those in saliva. Smaller food particles also travel more easily (and therefore more quickly) throughout the small and large intestines. In the stomach, food is mixed with gastric juices, containing digestive enzymes and hydrochloric acid. This mixture, known as chyme, is then actively pumped out of the stomach and into the small intestine. There, more enzymes and bile are mixed with the chyme, and breakdown of dietary proteins, fats and carbohydrates is completed. Some carbohydrates are not digested by human enzymes and will pass undigested into the colon.

Most nutrients are absorbed in the small intestine. Within about 4-6 hours of eating, what is left of the food passes into the large intestine, or colon. Waste material accumulates, water and electrolytes are absorbed and fecal matter is stored until it passes out through the rectum every 24-48 hours.

Microbe Role in GI Tract

The microbes present in the gastrointestinal tract have the potential to act in a positive, negative or neutral manner. Due to unfavorable conditions, microbes are not very prevalent in the stomach or upper small intestine. However, toward the lower small intestine, they begin to attain higher populations (10⁶-10⁸/gram of small intestinal contents) and in the colon they constitute about 10¹¹-10¹²/gram of colon contents (a very large number).

Considering the high number of microbes in the intestinal tract, what are their effects? It is known that microbes in the large intestine complete the digestion process on any food components that were not digested in the small intestine, such as lactose in lactose intolerant people or fibers resistant to the enzymes they encounter in the small intestine. There is evidence of non-digestive microbial activities as well. Certain intestinal microbes are known to produce vitamins. Also, in studies done with special microbe-free laboratory animals, evidence is strong that without normal microbial populations, the immune system functions poorly, and resistance to pathogenic bacteria is greatly reduced. Other evidence suggests that intestinal microbes might act on pre-carcinogenic or mutagenic (capable of inducing genetic mutation) compounds. Depending on the specific microbe, mutagenic or carcinogenic activity can be either increased or decreased.

Both lactobacilli and bifidobacteria are normal inhabitants of the healthy intestine. Although they are not the dominant genera in either the small or large intestine of adults (bifidobacteria are generally the dominant flora of breast-fed infants), they are non-pathogenic and their presence is correlated with many measures of health. The metabolic end products of their growth are organic acids (lactic and acetic acids) that tend to lower the pH of the intestinal contents, creating conditions less desirable for harmful bacteria.

The gastrointestinal tract also serves to bridge the gap between “inside the body” and “outside the body”. Along this interface, microbes and foreign antigens colonizing or passing through the GI tract interact with important components of the immune system. This interaction serves to prime or stimulate the immune system for optimal functioning. Normal microbial inhabitants of the GI tract also reinforce the barrier function of the intestinal lining, decreasing passage of bacteria or antigens from the intestine into the blood stream. This function has been suggested to decrease infections and possibly allergic reactions to food antigens.

The composition of a “healthy” gut microbiota remains to be defined. Although there is agreement that microbes are important to human health, with the exception of defined pathogens, the role that microbes play in health and disease remains to be fully elucidated. Different patterns of microbial colonization associated with disease states compared to healthy controls have been documented, but it is important to remember that a causal relationship has not been established. Disrupted microbiota (dysbiosis) associated with intestinal and systemic conditions has been identified in obesity, metabolic syndrome, nonalcoholic steatohepatitis (NASH), inflammatory bowel diseases, irritable bowel syndrome, atherosclerosis, type 1 diabetes, autism, allergy, asthma and celiac disease. However, it has proven easier to identify dysbiosis than patterns of microbial colonization associated with health. Definition of a healthy microbiota is important to probiotic advancement as it would provide a microbiological target for interventions. However, how to best define the health status of an individual’s microbiome is not currently known.

Probiotics & Dairy Products

Probiotic bacteria are frequently, but not always, chosen from bacteria that normally inhabit the gastrointestinal system of humans. Sometimes the term “probiotic” is used as a synonym to “commensal, beneficial bacteria”, but this is an incorrect usage. Commensal flora may be beneficial, but until they are isolated, characterized and shown in human studies to impart a health benefit, they cannot be accurately called “probiotic”. Also, probiotics must be safe.

Once destined for commercial use, these bacteria are purified, grown to large numbers, concentrated to high doses and preserved. They are provided in products in one of three basic ways:

as a culture concentrate added to a food at medium levels, with little or no opportunity for culture growth
inoculated into a milk-based food (or dietary supplement) and allowed to grow to achieve high levels in a fermented food
as concentrated and dried cells packaged as dietary supplements such as powders, capsules, or tablets, and delivered at a range of doses

Probiotic bacteria have a long history of association with dairy products. This is because some of the same bacteria that are associated with fermented dairy products also make their homes in different sites on the human body, including the mouth, the gastrointestinal tract and the vagina. Some of these microbes, therefore, can play a dual role in transforming milk into a diverse array of fermented dairy products (yogurt, cheese, kefir, etc.), and contributing to the important role of colonizing bacteria.

Dairy products may provide a desirable “probiotic delivery vehicle” for several reasons. To date, however, there is little research on the impact of delivery vehicle and probiotic efficacy for any of the possible formats. This is an important area for future research.

Dairy foods can protect the probiotic bacteria. Traveling through the human digestive tract can be a challenge for bacteria. High acid levels in the stomach and exposure to pancreatic secretions such as digestive enzymes and bile in the small intestine can lead to the injury and death of a percentage of orally administered probiotics. Although some bacteria are more resistant than others to this stress, consumption of probiotics with food, including milk, yogurt and other dairy products, buffers stomach acid and can increase the chance that the bacteria will survive into the intestine.

Refrigerated storage of dairy products helps promote probiotic stability. Although the lactic acid content of yogurt can be a barrier to culture stability, short-term refrigeration generally promotes stability.

Live cultures in dairy foods carry a positive image. The consuming public may have a generally negative image of bacteria in foods, but they are aware of “live, active cultures” in fermented dairy foods, and these cultures convey a positive, healthful image. Probiotic bacteria in dairy foods can be an extension of the comfortable association of cultures in dairy products, and make it easier to communicate health messages to the public.

The healthful properties of probiotic bacteria blend with the healthful properties of milk products. A dairy product containing probiotics makes a healthy, “functional food package.” In addition to the vitamins, calcium, other minerals, and protein obtained from milk products, modern research has suggested healthful properties of fermentation-derived peptides and butyric acid found in some dairy products. Dairy products have recently been shown to be important components for a healthy diet, for more than the prevention of osteoporosis. Consumption of three or more servings of dairy products each day has been associated with lower levels of obesity among Americans. Obesity is associated with diabetes, hypertension and heart disease. The DASH (Dietary Approaches to Stop Hypertension) diet also recommends three servings of lowfat dairy products.

Choosing a Probiotic

The potential benefits of probiotic cultures seem vast. The applications range from helping to treat acute intestinal infections to aiding in the digestion of lactose and contributing, over the longer term, to improved health and possibly reduced risk of disease.

What should be considered when choosing a probiotic? Microbiologists agree that it cannot be assumed that research published on one strain of probiotic applies to another strain, even of the same species. (Remember, for the strain “Lactobacillus rhamnosus GG”, the genus is Lactobacillus, the species is rhamnosus and the strain designation is GG. A different strain of L. rhamnosus may have different probiotic properties.) Therefore, documentation of type of bacteria (genus, species and strain), potency (number of viable bacteria per dose), purity (presence of contaminating or ineffective bacteria), and the extent of research that has been published on health effects, must be provided for any strain being used in a product. Usually the culture or product manufacturer can provide this information.

When needed, additional support for these questions can be obtained by contacting the California Dairy Research Foundation and their affiliated experts.

Health Effects of Probiotics

There have been hundreds of papers published on the characterization of and health benefits associated with probiotic cultures and the pace of publication of new papers is accelerating.Some of these publications describe clinical studies designed to determine how probiotic cultures may influence a variety of health conditions. These are very complicated questions, and research is still actively being conducted to clarify the role of probiotics in human health.

When considering the health effects of probiotics, it is important to recognize that different strains, species and genera of bacteria may have different effects. For the most part, specific clinical studies on probiotics are done with one defined strain or a defined combination of strains. The following discussion, therefore, should be taken as a general description of probiotic activity, keeping in mind that any one effect may have been documented with only one or a limited number of probiotic strains.

Although any one study may not give a complete picture of effectiveness, an evaluation of the body of research done on probiotics suggests that certain strains consumed at adequate levels positively influence human health. The following describes some of the researched health benefits of consumption of probiotic cultures.

Allergy

Allergy is on the rise in industrialized nations. It is estimated that the incidence of asthma in the United States doubled between 1980 and 2000. Scientists have proposed a hypothesis known as the ‘hygiene hypothesis’ to explain the rise in allergic conditions such as asthma and eczema. This hypothesis is based on observations that lower allergy incidence is associated with environments that have greater numbers of microbes, such as day care centers, farms, or in homes with siblings or pets. Sanitary living environments and the consumption of processed foods have limited the number of microbes in the diet. The hypothesis suggests that the exposure of infants to microbes before the age of six months helps the immune system mature to be more tolerant of exposure to allergens later in life (“Day Care May Boost Immunity To Asthma,” August 2000, Washington Post.) Certainly, microbial colonization of the gut in early life is important to the development of a properly functioning immune system (read more).

Of course, increasing exposure to microbes must be done safely. This hypothesis led researchers in Finland to conduct a study evaluating the effects of a Lactobacillus strain on incidence of atopic eczema in 132 infants at high risk of developing eczema. The study was double-blinded and placebo-controlled. Pregnant mothers two-to-four weeks before delivery and newborn babies through six months of age were given Lactobacillus rhamnosus GG. Infants were followed through two years of age and incidence of recurring atopic eczema was recorded. The study reported a 50% drop in incidence of recurring atopic eczema in the group receiving the probiotic supplement. A follow up study of these same children indicated that these same trends were still present at 4 years of age. However, no impact on other allergic conditions was observed through seven years of age. These results suggest that exposure to the right types of microbes early in life may decrease the risk of atopic dermatitis. However, a German research group using a very similar protocol and the same probiotic microbe as the Finnish group recently reported that no impact on incidence of atopic eczema was observed with supplementation with L. rhamnosus GG. In addition, the German study noted a statistically significant increase in wheezing in the probiotic group. This study calls into question the validity of the initial observation. An ongoing NIH-funded study in this same area will hopefully clarify a role of prevention of allergy in newborns by L. rhamnosus GG. The effects of probiotics on allergy have been reviewed.

Brain function

It may seem hard to believe, but evidence is emerging that the gut microbes can impact brain function. If we consider that the gut is known as our “second brain,” then perhaps this concept does not seem so far-fetched. The communication between the gut and the brain is bi-directional: the brain controls GI tract function (stress and emotions), but less obvious is that the gut can control pain and emotion. Of particular interest in the discussion of probiotics, is that gut microbes, and probiotics, have been shown to mediate some of this “bottom-up” communication.

For example, one study administered Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 for 30 days to healthy volunteers, who were assessed using validated questionnaires measuring different psychological scales in a randomized, double-blind, placebo-controlled design. The study found that the probiotic reduced somatisation, depression, anger–hostility, their self-blame and were more focused on the problem solving. Other studies showed probiotic impact on improved sleep in elderly volunteers, improved mood scores, and decreased anxiety in patients with chronic fatigue syndrome.

The role of probiotics on different aspects of brain function is an emerging area of research, and care should be taken not to over interpret early animal and pilot human studies, even though a plausible mechanism of action has been postulated.

Cancer

In general, cancer is caused by mutation or activation of abnormal genes that control cell growth and division. (A substance that causes a mistake in genes is known as a mutagen). Most of these abnormal cells do not result in cancer since normal cells usually out-compete abnormal ones. Also, the immune system recognizes and destroys most abnormal cells.

Many processes or exposures can increase the occurrence of abnormal cells. Precautions that minimize these exposures decrease the risk of cancer. Among the many potentially risky exposures are chemical exposures. Cancer-causing chemicals (carcinogens) can be ingested or generated by metabolic activity of microbes that live in the gastrointestinal tract. It has been hypothesized that probiotic cultures might decrease the exposure to chemical carcinogens by (1) detoxifying ingested carcinogens, (2) altering the environment of the intestine and thereby decreasing populations or metabolic activities of bacteria that may generate carcinogenic compounds, (3) producing metabolic products (e.g., butyrate) which improve a cell’s ability to die when it should die (a process known as apoptosis or programmed cell death), (4) producing compounds that inhibit the growth of tumor cells, or (5) stimulating the immune system to better defend against cancer cell proliferation.

Research suggests that the consumption of probiotic cultures may decrease cancer risk. Researchers testing the effect of the consumption of fermented milks, probiotic bacteria, components of bacteria or extracts of bacteria have found:

A reduction in the incidence of chemically induced tumors in rats.
A reduction of the activity of fecal enzymes (β-glucuronidase, azoreductase, nitroreductase, and 7-α-dehydrogenase) postulated to play a role in colon cancer in human and animal subjects.
Degradation of nitrosamines.
A weakening of mutagenic activity of substances tested in the laboratory.
Prevention of damage to DNA in certain colonic cells.
In vitro binding of mutagens by cell wall components of probiotic bacteria.
Enhancement of immune system functioning.

Taken together, these results suggest that probiotic cultures may positively influence the gastrointestinal environment to decrease the risk of cancer. However, cancer reduction must be demonstrated in humans to confirm the significance of these observations. The impact of consumption of milk fermented by Lactobacillus caseiShirota on recurrence of superficial bladder cancer was tested. The recurrence-free period for the Lactobacillus-consuming group was found to be almost twice as long as the control group. In another study, this same strain was found to decrease atypical recurrent polyps in subjects with previous history of colonic polyp (Ishikawa et al. 2005). The European Union (EU)-sponsored Synbiotics and Cancer Prevention in Humans project tested a synbiotic (oligofructose plus L. rhamnosus GG and Bifidobacterium lactis Bb12) in patients at risk for colonic polyps and looked at intermediate end points that can be used as biomarkers of colon cancer risk. This study found that the synbiotic decreased uncontrolled growth of intestinal cells. These results must still be considered preliminary, but are encouraging that impacting the colonic environment may improve cancer occurrence.

Common infectious disease

Often people wonder if probiotics have any benefit for healthy people. Perhaps the most compelling line of research suggesting such benefit is with studies conducted on healthy subjects, such as children in school or day care, and tracking how often they experience symptoms associated with colds and mild flu. Numerous such studies have been conducted on a variety of different probiotic preparations. A meta-analysis was published on probiotics and preventing acute upper respiratory tract infections. After reviewing 14 human trials, it concluded that probiotics reduced episodes of acute upper respiratory tract infections and reduced antibiotic use.

Probiotics have also been evaluated in at-risk populations. For example, Saran et al. showed that a probiotic-containing food could improve growth parameters for undernourished children. Sur et al. showed that probiotics can help prevent acute diarrhea in children in an urban slum in India.

Taken together, these controlled human studies provide support that certain probiotic strains can help avoid acute common infectious illnesses. This effect is likely mediated by immune enhancement functions or direct inhibition of pathogens, but mechanistic studies have not always accompanied positive clinical indications.

Diarrhea

Many types of diarrheal illnesses, with many different causes, disrupt intestinal function. The ability of probiotics to decrease the incidence or duration of certain diarrheal illnesses is perhaps the most substantiated of the health effects of probiotics (read more). A paper published in 2002 reviewed nine studies on the effect ofLactobacillus as therapy for diarrhea in children. This paper concluded that “Lactobacillus is safe and effective as a treatment for children with acute infectious diarrhea.” Although this meta-analysis can be criticized for combining data from different species and strains of Lactobacillus into one analysis, the positive nature of the conclusion suggests that at least for this indication and for these strains, positive results have been obtained.

One common form of diarrhea is that associated with the consumption of antibiotics. The purpose of antibiotics is to kill harmful bacteria. Unfortunately, they can kill normal bacteria as well, and consequently disturb normal intestinal function. (Note that it is certainly NOT true that antibiotics “wipe out” all your normal flora, but they can act broadly and exact a toll on your normal, non-pathogenic bacteria.) It is important to realize that the microbiota of the healthy person is quite resilient and will return to a pre-antibiotic status with no intervention. But it is hypothesized that supplementing the intestine with probiotics might help stabilize the antibiotic-induced dysbiosis and minimize disruptive effects. One recent study documented that a probiotic containing four Lactobacillus and Bifidobacterium strains did lead to a quicker return to normal microbiota in antibiotic-consuming adults (read more). A paper published in 2002 reviewed seven studies (881 total patients) on the impact of probiotics (Lactobacillus rhamnosus GG or Saccharomyces boulardii) on antibiotic-associated diarrhea (read more). The paper concluded that probiotics can be used to prevent antibiotic-associated diarrhea, but that no strong effect on the ability of probiotics to treat such diarrhea exists. How these probiotics accomplish this task is not known. Not all studies have shown positive results in the prevention of antibiotic associated diarrhea or other symptoms associated with antibiotic therapy (read more).

A serious complication of antibiotic therapy can be the onset of colitis due toClostridium difficile. This condition can be refractory to subsequent antibiotic treatment, resulting in ongoing recurrences. A few small studies have suggested that certain probiotics can prevent relapses of C. difficile colitis. A recent metaanalysis concluded that the probiotic yeast, Saccharomyces boulardii was the most effective probiotic treatment (read more).

Another common form of diarrhea is experienced by travelers. Studies evaluating the effect of probiotics on travelers’ diarrhea are equivocal. There is a need for further research in this area for more convincing findings. One metaanalysis of 12 studies on travelers’ diarrhea concluded that certain probiotic products may offer a safe and effective method to prevent traveller’s diarrhea with no indication of serious adverse events (read more).

Elevated Blood Cholesterol

Cholesterol is essential for many functions in the human body. It acts as a precursor to certain hormones and vitamins and it is a component of cell membranes and nerve cells. However, elevated levels of total blood cholesterol or other blood lipids are considered risk factors for developing coronary heart disease. Although humans synthesize cholesterol to maintain minimum levels for biological functioning, diet also is known to play a role in serum cholesterol levels. The extent of influence varies significantly from person to person. Probiotic cultures have been evaluated for their effect on serum cholesterol levels. Clinical studies on the effect of lowering cholesterol or low-density lipid levels in humans have not been conclusive (read more). There have been some human studies that suggest that blood cholesterol levels can be reduced by consumption of probiotic-containing dairy foods by people with elevated blood cholesterol, but in general the evidence is not overwhelming. It is likely that some strains may demonstrate this property while others do not, or that only subsets of people with elevated cholesterol respond.

Helicobacter pylori

Helicobacter pylori is a bacterium which colonizes the stomach and can cause gastric ulcers and gastric cancer. The effect of probiotics on H. pylori has been studied. Mechanistic studies in laboratory assays or in animal models have shown that antibacterial substances including (but not limited to) organic acids produced by some lactobacilli inhibit the growth and survival of this pathogen. When tested in humans, results are mixed. Results in humans suggest that some probiotic strains or milk fermented with a probiotic strain can reduce metabolic activity or colonization by H. pylori but eradication has not been achieved (read more). Probiotics have also been used to manage side effects of triple antibiotic therapy used to treat H. pylori infections. In these studies, the use of probiotics decreases the side effects of antibiotics, improves patient compliance with taking the prescribed therapy, and increases the rate at which H. pylori is eradicated (read more).

Hypertension

About 50-60 million people in United States are estimated to have hypertension, or elevated blood pressure. Antihypertensive effects have been documented in animal models and in mildly hypertensive adults for three compounds derived from the growth of certain lactobacilli (read more): 1) fermented milk containing two tripeptides derived from the proteolytic action of L. helveticus on casein in milk (read more); 2) bacterial cell wall components from cell extracts of lactobacilli; and 3) fermented milk containing fermentation-derived gamma-amino butyric acid. Systolic blood pressure was decreased on the order of 10-20 mm Hg. These results suggest that consumption of certain lactobacilli, or products made from them, may reduce blood pressure in mildly hypertensive people. Viability of the Lactobacillus is not required for the effect.

Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a functional bowel disorder that can be characterized by symptoms of abdominal pain, cramps, gas, bloating, diarrhea and constipation. Surveys estimate the prevalence rate ranging from 10-20% of the adult population and the condition is diagnosed 3 times more often in women than men. Only a few controlled studies have been conducted evaluating probiotics and IBS. Some symptom relief (primarily from diarrhea or abdominal pain or bloating) has been reported in studies published to date.

Inflammatory Bowel Disease

Inflammatory bowel diseases such as ulcerative colitis and Crohnâ€™s disease, are serious intestinal diseases that can lead to the surgical removal of the colon. The cause of these diseases is not known but it has been hypothesized that an intolerance to the normal microbiota in the gut leads to inflammation and resulting pathology. Efforts to identify a single microbe associated with the disease has failed, leading some to suggest that it is a pathogenic microbial community, not a single microbe, that is responsible for IBD. The role of gut flora in the progression of these diseases has led some researchers to study the impact certain probiotic bacteria might have on maintaining the state of reduced inflammation that occurs during remission stages of the diseases. Several controlled, clinical trials have shown that high levels of certain probiotic strains can extend the disease-free remission period. Studies also have documented this effect on remission of pouchitis. But not all studies have shown benefits.

Immune System Modulation

The immune system defends against microbial pathogens that have entered our bodies. The immune system is extremely complex, involving both cell-based and antibody-based responses to potential infectious agents. Immunodeficiency can result from certain diseases (e.g., cancer, AIDS, leukemia) or, to a lesser extent, from more normal conditions such as old age, pregnancy, or stress. Autoimmune diseases (e.g., allergies, rheumatoid arthritis, inflammatory bowel diseases) also can occur due to misdirected immune system activity.

Probiotic cultures have been shown in a variety of test systems to stimulate certain cellular, biochemical and antibody functions of the immune system (read more). Animal and some human studies have shown an effect of yogurt or lactic acid bacteria on enhancing levels of certain immunoreactive cells (e.g. macrophages, lymphocytes) or on regulation of immune factors (cytokines, immunoglobulins, interferon). In addition, some studies have shown improved survival of pathogen-infected laboratory animals consuming probiotic cultures as compared to animals consuming a control diet. Results accumulated so far suggest that probiotics may provide an additional tool to help your body protect itself.

An exciting area of research has been documenting the ability of certain probiotic bacteria to modulate immune dysregulation. Studies have shown that probiotics are effective in decreasing the development of allergy and relapse of inflammatory bowel disease.

Kidney Stones

High levels of oxalate in the urine is a risk factor for the development of kidney stones. Utilization of oxalate by intestinal microbes limits its absorption. A probiotic preparation that contained bacteria that were able to degrade oxalate in vitro was shown to reduce oxalate fecal excretion in six patients. These results suggest that manipulation of the gut flora with the right probiotic bacteria may have a positive impact on gastrointestinal tract oxalate levels and may decrease oxalate absorption (read more). These results are intriguing, but preliminary.

Lactose Intolerance

The inability of adults to digest lactose, or milk sugar, is prevalent worldwide. People of northern European descent are unique in retaining the ability to produce the lactose-digesting enzyme, lactase, into adulthood. Consumption of lactose by those lacking adequate levels of lactase produced in the small intestine can result in symptoms of diarrhea, bloating, abdominal pain and flatulence. These symptoms are due to undigested lactose reaching the large intestine and being fermented by the colonic microbes. These microbes can produce gases and products that lead to watery stool.

The inability to comfortably consume dairy products not only limits people’s freedom to choose preferred foods, but also potentially compromises calcium intake, threatening bone health. It has been documented scientifically that many lactose intolerant individuals are better able to consume fermented dairy products, such as yogurt, with fewer symptoms than the same amount of unfermented milk, even though yogurt contains about the same amount of lactose as milk (read more). Yogurt was found to aid digestion of lactose because the lactic acid bacteria used to make yogurt deliver lactase to the small intestine, where it breaks down the lactose before it reaches the colon. In addition to yogurt starter bacteria, L. acidophilus and bifidobacteria have been shown by several studies to improve digestion of lactose, although generally to a lesser extent than the yogurt starter cultures, Lactobacillus bulgaricus and Streptococcus thermophilus.

Obesity and metabolic syndrome

Perhaps one of the most fascinating areas of research on the gut microbiota and health is how colonizing microbes might impact the onset of obesity and metabolic syndrome. Disrupted patterns of colonization are associated, for example, with obesity and diabetes, but what is not clear is if strategies to alter the disrupted microbiota can impact the course of these conditions. Microbes may directly impact energy harvest from foods due to bacterial metabolism in the gut. But microbes or their products may also act as metabolic regulators through interacting with host cellular targets. Some experimental animal model studies have looked at the effect of probiotics on obesity. In humans, a strain of Lactobacillus gasseri was shown to decrease fat mass (visceral and subcutaneous) and BMI in diabetic patients . In another human study, a probiotic preserved insulin sensitivity. This is a field of research with promise, but still in its infancy.

Necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is a gastrointestinal disease that mostly affects premature infants. It is characterized by infection and inflammation leading to death of tissue of the large intestine. Probiotic supplementation may reduce the risk of NEC in preterm infants. A recent review of studies targeting efficacy and safety of probiotics for infants at risk for developing NEC was conducted (read more). Taken together, studies suggest that probiotics lower the risk of mortality in preterm infants, but additional studies on best strains for this application, short- and long-term safety and required dose must be conducted.

Oral health

One study conducted with children aged 3-6 years in day care centers evaluated the ability of milk containing L. rhamnosus GG to reduce the incidence of dental caries (read more). Only a subset of the study group, children aged 3-4 years, showed any statistically significant reduction in dental caries incidence. Other studies have documented that other probiotics, e.g., L. reuteri or Bifidobacterium animalis DN173 010, can reduce salivary levels of cariogenic Streptococcus mutans in young adults (read more).

Small Bowel Bacterial Overgrowth

Under certain conditions (production of low stomach acid, kidney dialysis and others), microbial populations in the small intestine can increase beyond normal levels. This is termed small bowel bacterial overgrowth. The misplaced microbes can produce byproducts from their growth that can be toxic. Researchers have found that feeding high levels of certain probiotic strains can control the toxic effects of these microbes (read more). This is another example of the ability of probiotic strains fed in high numbers to modulate the activity of other intestinal bacteria.

Vaginosis

The vagina and its microbiota form a finely balanced ecosystem. Disruption of this ecosystem can lead to a microbiological imbalance and symptoms of vaginosis. Vaginosis used to be considered a mere annoyance, but now is being examined for a role in serious conditions including pelvic inflammatory disease, pregnancy-related complications (such as low birth weight babies), and increased susceptibility to AIDS infection. Vaginosis can be caused by several different organisms, and in many cases, the causative agent may not be identified. What is known is that lactobacilli predominate in the healthy vagina, and a lack of lactobacilli is a risk factor for vaginosis. The lactobacilli are thought to maintain a favorable vaginal pH in the acidic range and to inhibit pathogens, possibly through the production of hydrogen peroxide and other antimicrobial factors. The most conclusive human studies to date on the impact of lactobacilli on bacterial vaginosis showed that Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 administered in milk could pass through the intestine, ascend to the vagina and restore a normal lactobacilli microbiota in women prone to infections (read more). These strains were delivered in yogurt to African women with bacterial vaginosis and shown to improve therapeutic outcome (read more). These studies have provided the best evidence to date for successful probiotic intervention to improve vaginal health. Some other recent studies have not shown positive results (read more), highlighting the importance of use of effective strains and delivery systems.

Probiotics Basics