Lactobacillus reuteri
Encyclopedia
Lactobacillus reuteri is a Gram-positive
bacterium that naturally inhabits the gut
of mammal
s and bird
s. First described in the early 1980s, some strains of L. reuteri are used as probiotic
s. BioGaia AB in Sweden owns several commercially important strain
s and a large number of different patent
s for commercial usage of L. reuteri.
As early as the turn of the 20th century, L. reuteri was recorded in scientific classifications of lactic acid bacteria
, though at this time it was mistakenly grouped as a member of Lactobacillus fermentum.
In the 1960s, further work by German microbiologist
Gerhard Reuter – for whom the species eventually would be named – began to distinguish L. reuteri from L. fermentum. Reuter re-classified the species as "Lactobacillus fermentum biotype II".
L. reuteri was eventually identified as a distinct species in 1980 by Kandler et al. This group found significant differences between L. reuteri and other biotypes of L. fermentum, and thus proposed that it be given formal species identity. They chose the species name "reuteri", after discoverer Gerhard Reuter, and L. reuteri has since been recognized as a separate species within the Lactobacillus genus
.
Interest in L. reuteri began to increase as scientists began to find it colonizing the intestine
s of healthy animals. Gerhard Reuter first isolated L. reuteri from human fecal and intestinal samples in the 1960s, and this work was later repeated by other researchers. The same experiments – attempting to isolate L. reuteri from feces and intestine of healthy animals – were also done for non-human species, proving that L. reuteri seems to be present almost universally throughout the animal kingdom. For example, L. reuteri was discovered to be present naturally in the intestines of healthy sheep, chickens, pig
s, and rodent
s.
Furthermore, a study searching for 18 major species of gut flora, including Lactobacillus acidophilus
, in a variety of animals found that L. reuteri was the only bacterium that constituted a "major component" of the Lactobacillus species present in the gut of each of the host animals tested. L. reuteri is now well-established as one of the most ubiquitous members of the naturally-occurring gut bacteria.
A related discovery is that each animal host seems to have a host-specific strain of L. reuteri, e.g. a rat strain for rats, a pig strain for pigs, etc. The universality of L. reuteri, in conjunction with this evolved host-specificity, has led scientists to make inferences about its importance in promoting the health of the host organism.
, Ivan Casas, and their colleagues discovered that L. reuteri produced a novel broad-spectrum antibiotic
substance via the organism's fermentation
of glycerol
. They named this substance "reuterin
", also after Gerhard Reuter. Reuterin is a multi-compound dynamic equilibrium
(HPA system, HPA) consisting of 3-hydroxypropionaldehyde, its hydrate, and its dimer. At concentrations above 1.4 M, the HPA dimer was predominant. However, at concentrations relevant for biological systems, HPA hydrate was the most abundant, followed by the aldehyde form.
Reuterin, it was found, inhibits the growth of some harmful Gram-negative and Gram-positive bacteria, along with yeast
s, fungi, and protozoa
. Naturally, a gut organism capable of fighting off other, harmful gut organisms was of great interest. Researchers found that L. reuteri can indeed secrete sufficient amounts of reuterin to cause the desired anti-microbial effects. Furthermore, since about 4-5 times the amount of reuterin is needed to kill "good" gut bacteria (i.e. L. reuteri and other Lactobacillus species) as "bad", this would allow L. reuteri to remove gut invaders while keeping normal gut flora intact.
Some studies have called into question whether or not reuterin production is essential for L. reuteri 's health-promoting activity. However, the discovery that it naturally produces an antibiotic substance was nevertheless important, as it has led to a great deal of further research on L. reuteri. In fact, in early 2008 it was confirmed that L. reuteri is capable of producing reuterin in the gastrointestinal tract
, and that this improves its ability to inhibit the growth of E. coli
.
The gene cluster controlling the biosynthesis of reuterin and cobalamin in the L. reuteri genome is a genomic island
acquired from an anomalous source.
, although the amount of the bacterium present in the body returns to low levels within several months after intake is stopped. Furthermore, L. reuteri is found in breast milk
, and oral intake on the mother's part likewise increases the amount of L. reuteri present in her milk, and the likelihood that it will be transferred to the child's body.
Once present in the body, L. reuteri benefits its host in a variety of ways, particularly by fighting off harmful infections and mediating the body's immune system
.
Safety
L. reuteri has been tested for host tolerance in children, healthy adults, and the immunosuppressed (HIV
patients). No adverse serious medical consequences have been observed up to the maximum tested dosage of 1010 colony-forming unit
s per day, and there were no significant differences in standard medical laboratory tests including complete blood count
, urinalysis
, complete metabolic panel, and liver function tests
between those subjects given L. reuteri and those given placebo. Gastrointestinal side effects were reported in some patients; there was an increased incidence of bowel gas (flatulence
) in the healthy adults, and an increase in nausea
was seen in the HIV patients.
Intestinal effects
One of the most well-documented effects of L. reuteri is in the treatment of rotavirus
-induced diarrhea, especially in children. Treatment of rotaviral diarrhea
by consumption of L. reuteri significantly shortens the duration of the illness as compared to placebo
. Furthermore, this effect is dose-dependent: the more L. reuteri consumed, the faster the diarrhea stops. L. reuteri is also effective as a prophylactic for this illness; children fed L. reuteri while healthy are less likely to fall ill with diarrhea in the first place. With regard to prevention of gut infections, comparative research has found L. reuteri to be more potent than other probiotic organisms .
L. reuteri is also an effective treatment against infant colic
. Over a period of several weeks, infants who are given L. reuteri steadily decrease the amount of time each day spent crying – the defining symptom of colic. In fact L. reuteri was much better in decreasing the infants' crying time than the standard therapy of simethicone
treatment. A randomized, double-blind, placebo controlled trial of fifty exclusive breast fed colicky infants found a significant decrease in daily crying time amounts when treated with L. reuteri DSM 17 938 compared with placebo. It further found a significant increase in lactobacilli colonization, a decrease in fecal Escherichia coli
and ammonia
when compared with placebo. However, colic is still poorly understood, and it is not clear why or through what mechanism L. reuteri ameliorates its symptoms. One theory of colic, though, holds that affected infants cry because of severe gastro-intestinal discomfort; if this is indeed the case, it is quite plausible that L. reuteri somehow acts to lessen this discomfort, since its primary residence is inside the gut.
There is conflicting evidence as to whether L. reuteri is capable of eradicating the gut pathogen
Helicobacter pylori
, which causes peptic ulcers and is endemic in parts of the developing world. One study showed that dietary supplementation of L. reuteri alone reduces, but does not fully eradicate, H. pylori in the gut. Another study found that adding L. reuteri to omeprazole
therapy dramatically increased (from 0% to 60%) the cure rate of H. pylori-infected patients compared to the drug alone. However, this result has since been contradicted by a follow-up study, which showed no benefit of adding L. reuteri to traditional antibiotic therapy for H. pylori eradication.
Oral health
L. reuteri may also be capable of promoting dental health, as it has been proven to kill Streptococcus mutans
, a bacterium responsible for tooth decay. A screen of several probiotic bacteria found that L. reuteri was the only species of those tested able to block S. mutans. Before testing in humans was begun, another study showed that L. reuteri had no harmful effects on teeth. Clinical trials have since proven that those people whose mouths are colonized with L. reuteri (via dietary supplementation) have significantly less of the harmful S. mutans. Since these studies have been short-term, it is not yet known whether L. reuteri prevents tooth decay. However, since L. reuteri is able to reduce the numbers of an important decay-causing bacterium, this would be expected.
Gingivitis
also may be ameliorated by consumption of L. reuteri. Patients afflicted with severe gingivitis showed decreased gum
bleeding, plaque
formation, and other gingivitis-associated symptoms compared with placebo after chewing gum
containing L. reuteri.
General health
By protecting against many common infections, L. reuteri promotes overall wellness in both children and adults. Double-blind
, randomized studies in child care centers have found that L. reuteri-fed infants fall sick less often, require fewer doctor visits, and are absent fewer days from the day care center compared to placebo and to the competing probiotic Bifidobacterium lactis.
Similar results have been found in adults; adults consuming L. reuteri daily end up falling ill 50% less often, as measured by their decrease use of sick leave.
) may obviously not be conducted in human
s. Therefore, many of the benefits of L. reuteri have been studied only in different animal species, such as pigs and mice
. Given the similarity of mammal
ian species, however, it is likely – though not scientifically proven – that these benefits hold true for humans as well.
In general, animal studies on L. reuteri are done using the species-specific strain of the bacterium (see above).
Protection against pathogens
L. reuteri confers a high level of resistance to the pathogen
Salmonella typhimurium, halving mortality rate
s in mice. The same is true for chickens and turkeys; L. reuteri greatly moderates the morbidity and mortality caused by this dangerous food-bourne pathogen.
L. reuteri is also effective in stopping harmful strains of E. coli from affecting its host. A study performed in chickens showed that L. reuteri was as potent as the antibiotic gentamicin
in preventing E. coli-related deaths.
The protozoic parasite Cryptosporidium parvum
causes severe watery diarrhea, which can become life-threatening if the patient is immunocompromised
(as in individuals infected with HIV
). L. reuteri is known to lessen the symptoms of C. parvum in mice and pigs. Given that there is no known direct treatment for C. parvum (the antibiotic Paromomycin has limited effect), L. reuteri may prove valuable in protecting patients suffering from this disease.
Some protective effect against the yeast Candida albicans
has been found in mice, but in this case L. reuteri did not work as well as other probiotic organisms such as L. acidophilus and L. casei.
General health
In young commercial livestock
such as turkey chicks and piglets, body weight
and growth rate are good indicators of the health of the animal. Animals raised in the dirty, crowded environments of commercial farms
are generally less healthy (and therefore weigh less) than their counterparts born and bred in cleaner homes. In turkeys, for example, this phenomenon is known as "poult growth depression", or PGD.
Supplementing the diets of these young farm animals with L. reuteri helps them to largely overcome the stresses imposed by their unhealthy habitats. Commercial turkeys fed L. reuteri from birth had nearly a 10% higher adult body weight than their peers raised in the same conditions. A similar study on piglets showed that L. reuteri is at least as effective as synthetic antibiotics in improving body weight under crowded conditions .
The mechanism by which L. reuteri is able to support the healthy growth of these animals is not entirely understood. It is possible that L. reuteri simply serves to protect livestock against illness caused by Salmonella typhimurium and other pathogens (see above), which are much more common in crowded commercial farms. However, other studies have revealed that L. reuteri can also help when the growth depression is caused entirely by a lack of dietary protein
, and not by contagious disease. This raises the possibility that L. reuteri somehow improves the intestines' ability to absorb and process nutrient
s .
Effect on chemical and trauma-induced injury
Treating colon
ic tissue from rats with acetic acid
causes an injury similar to the human condition ulcerative colitis
. Treating the injured tissue with L. reuteri immediately after removing the acid almost completely reverses any ill effects, leading to the possibility that L. reuteri may be beneficial in the treatment of human colitis patients.
In addition to its role in digestion
, the intestinal wall is also vital in preventing harmful bacteria, endotoxins, etc., from "leaking" into the bloodstream. This leaking, known as bacterial "translocation", is very dangerous and can lead to lethal conditions such as sepsis
. In humans, translocation is more likely to occur following such events as liver
injury and ingestion of some poison
s. In rodent studies, L. reuteri was found to greatly reduce the amount of bacterial translocation following either the surgical removal of the liver or injection with D-galactosamine
, a chemical which also causes liver damage.
The anti-cancer
drug methotrexate
causes severe enterocolitis
in high doses. L. reuteri greatly mitigates the symptoms of methotrexate-induced enterocolitis in rats, one of which is bacterial translocation.
Gram-positive
Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...
bacterium that naturally inhabits the gut
Gut (zoology)
In zoology, the gut, also known as the alimentary canal or alimentary tract, is a tube by which bilaterian animals transfer food to the digestion organs. In large bilaterians the gut generally also has an exit, the anus, by which the animal disposes of solid wastes...
of mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s and bird
Bird
Birds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from...
s. First described in the early 1980s, some strains of L. reuteri are used as probiotic
Probiotic
Probiotics are live microorganisms thought to be beneficial to the host organism. According to the currently adopted definition by FAO/WHO, probiotics are: "Live microorganisms which when administered in adequate amounts confer a health benefit on the host"...
s. BioGaia AB in Sweden owns several commercially important strain
Strain (biology)
In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...
s and a large number of different patent
Patent
A patent is a form of intellectual property. It consists of a set of exclusive rights granted by a sovereign state to an inventor or their assignee for a limited period of time in exchange for the public disclosure of an invention....
s for commercial usage of L. reuteri.
Discovery
Though the species Lactobacillus reuteri has been recognized for some time, knowledge of its probiotic properties did not come until much later.As early as the turn of the 20th century, L. reuteri was recorded in scientific classifications of lactic acid bacteria
Lactic acid bacteria
The lactic acid bacteria comprise a clade of Gram-positive, low-GC, acid-tolerant, generally non-sporulating, non-respiring rod or cocci that are associated by their common metabolic and physiological characteristics. These bacteria, usually found in decomposing plants and lactic products, produce...
, though at this time it was mistakenly grouped as a member of Lactobacillus fermentum.
In the 1960s, further work by German microbiologist
Microbiology
Microbiology is the study of microorganisms, which are defined as any microscopic organism that comprises either a single cell , cell clusters or no cell at all . This includes eukaryotes, such as fungi and protists, and prokaryotes...
Gerhard Reuter – for whom the species eventually would be named – began to distinguish L. reuteri from L. fermentum. Reuter re-classified the species as "Lactobacillus fermentum biotype II".
L. reuteri was eventually identified as a distinct species in 1980 by Kandler et al. This group found significant differences between L. reuteri and other biotypes of L. fermentum, and thus proposed that it be given formal species identity. They chose the species name "reuteri", after discoverer Gerhard Reuter, and L. reuteri has since been recognized as a separate species within the Lactobacillus genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
.
L. reuteri as a "universal" gut organism
In the early 1980s, shortly after its recognition as a distinct species, scientists began to find L. reuteri in many natural environments. L. reuteri has been isolated from many foods, especially meat and milk products.Interest in L. reuteri began to increase as scientists began to find it colonizing the intestine
Intestine
In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...
s of healthy animals. Gerhard Reuter first isolated L. reuteri from human fecal and intestinal samples in the 1960s, and this work was later repeated by other researchers. The same experiments – attempting to isolate L. reuteri from feces and intestine of healthy animals – were also done for non-human species, proving that L. reuteri seems to be present almost universally throughout the animal kingdom. For example, L. reuteri was discovered to be present naturally in the intestines of healthy sheep, chickens, pig
Pig
A pig is any of the animals in the genus Sus, within the Suidae family of even-toed ungulates. Pigs include the domestic pig, its ancestor the wild boar, and several other wild relatives...
s, and rodent
Rodent
Rodentia is an order of mammals also known as rodents, characterised by two continuously growing incisors in the upper and lower jaws which must be kept short by gnawing....
s.
Furthermore, a study searching for 18 major species of gut flora, including Lactobacillus acidophilus
Lactobacillus acidophilus
Lactobacillus acidophilus is a species in the genus Lactobacillus. L. acidophilus is a homofermentative species, fermenting sugars into lactic acid, which grows readily at rather low pH values and has an optimum growth temperature of 37 °C . L...
, in a variety of animals found that L. reuteri was the only bacterium that constituted a "major component" of the Lactobacillus species present in the gut of each of the host animals tested. L. reuteri is now well-established as one of the most ubiquitous members of the naturally-occurring gut bacteria.
A related discovery is that each animal host seems to have a host-specific strain of L. reuteri, e.g. a rat strain for rats, a pig strain for pigs, etc. The universality of L. reuteri, in conjunction with this evolved host-specificity, has led scientists to make inferences about its importance in promoting the health of the host organism.
L. reuteri as an anti-microbial agent
In the late 1980s, Walter DobrogoszWalter Dobrogosz
Walter Dobrogosz is a Professor Emeritus of North Carolina State University, best known for his discovery and further research on the probiotic bacterium Lactobacillus reuteri.-Professional life:...
, Ivan Casas, and their colleagues discovered that L. reuteri produced a novel broad-spectrum antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
substance via the organism's fermentation
Fermentation (biochemistry)
Fermentation is the process of extracting energy from the oxidation of organic compounds, such as carbohydrates, using an endogenous electron acceptor, which is usually an organic compound. In contrast, respiration is where electrons are donated to an exogenous electron acceptor, such as oxygen,...
of glycerol
Glycerol
Glycerol is a simple polyol compound. It is a colorless, odorless, viscous liquid that is widely used in pharmaceutical formulations. Glycerol has three hydroxyl groups that are responsible for its solubility in water and its hygroscopic nature. The glycerol backbone is central to all lipids...
. They named this substance "reuterin
Reuterin
Reuterin is a potent antimicrobial multi-compound produced by Lactobacillus reuteri, during the metabolism of glycerol to 1,3-propanediol catalysed by the coenzyme B12-dependent diol dehydrase. Reuterin consists of 3-hydroxypropionaldehyde, its hydrate, and its dimer in dynamic equilibrium...
", also after Gerhard Reuter. Reuterin is a multi-compound dynamic equilibrium
Chemical equilibrium
In a chemical reaction, chemical equilibrium is the state in which the concentrations of the reactants and products have not yet changed with time. It occurs only in reversible reactions, and not in irreversible reactions. Usually, this state results when the forward reaction proceeds at the same...
(HPA system, HPA) consisting of 3-hydroxypropionaldehyde, its hydrate, and its dimer. At concentrations above 1.4 M, the HPA dimer was predominant. However, at concentrations relevant for biological systems, HPA hydrate was the most abundant, followed by the aldehyde form.
Reuterin, it was found, inhibits the growth of some harmful Gram-negative and Gram-positive bacteria, along with yeast
Yeast
Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...
s, fungi, and protozoa
Protozoa
Protozoa are a diverse group of single-cells eukaryotic organisms, many of which are motile. Throughout history, protozoa have been defined as single-cell protists with animal-like behavior, e.g., movement...
. Naturally, a gut organism capable of fighting off other, harmful gut organisms was of great interest. Researchers found that L. reuteri can indeed secrete sufficient amounts of reuterin to cause the desired anti-microbial effects. Furthermore, since about 4-5 times the amount of reuterin is needed to kill "good" gut bacteria (i.e. L. reuteri and other Lactobacillus species) as "bad", this would allow L. reuteri to remove gut invaders while keeping normal gut flora intact.
Some studies have called into question whether or not reuterin production is essential for L. reuteri 's health-promoting activity. However, the discovery that it naturally produces an antibiotic substance was nevertheless important, as it has led to a great deal of further research on L. reuteri. In fact, in early 2008 it was confirmed that L. reuteri is capable of producing reuterin in the gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
, and that this improves its ability to inhibit the growth of E. coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
.
The gene cluster controlling the biosynthesis of reuterin and cobalamin in the L. reuteri genome is a genomic island
Genomic island
A Genomic island is part of a genome that has evidence of horizontal origins. The term is usually used in microbiology, especially with regard to bacteria. A GI can code for many functions, can be involved in symbiosis or pathogenesis, and may help an organism's adaptation. Many sub-classes of...
acquired from an anomalous source.
Clinical results in humans
Although L. reuteri occurs naturally in humans, it is not found in all individuals. Therefore, dietary supplementation is needed to introduce and maintain high levels of L. reuteri in some people. Oral intake of L. reuteri has been shown to effectively colonize the intestine of healthy people; colonization begins rapidly within days of ingestionIngestion
Ingestion is the consumption of a substance by an organism. In animals, it normally is accomplished by taking in the substance through the mouth into the gastrointestinal tract, such as through eating or drinking...
, although the amount of the bacterium present in the body returns to low levels within several months after intake is stopped. Furthermore, L. reuteri is found in breast milk
Breast milk
Breast milk, more specifically human milk, is the milk produced by the breasts of a human female for her infant offspring...
, and oral intake on the mother's part likewise increases the amount of L. reuteri present in her milk, and the likelihood that it will be transferred to the child's body.
Once present in the body, L. reuteri benefits its host in a variety of ways, particularly by fighting off harmful infections and mediating the body's immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
.
Safety
L. reuteri has been tested for host tolerance in children, healthy adults, and the immunosuppressed (HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
patients). No adverse serious medical consequences have been observed up to the maximum tested dosage of 1010 colony-forming unit
Colony-forming unit
In microbiology, colony-forming unit is a measure of viable bacterial or fungal numbers. Unlike direct microscopic counts where all cells, dead and living, are counted, CFU measures viable cells...
s per day, and there were no significant differences in standard medical laboratory tests including complete blood count
Complete blood count
A complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...
, urinalysis
Urinalysis
A urinalysis , also known as Routine and Microscopy , is an array of tests performed on urine, and one of the most common methods of medical diagnosis...
, complete metabolic panel, and liver function tests
Liver function tests
Liver function tests , are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver. The parameters measured include PT/INR, aPTT, albumin, billirubin and others...
between those subjects given L. reuteri and those given placebo. Gastrointestinal side effects were reported in some patients; there was an increased incidence of bowel gas (flatulence
Flatulence
Flatulence is the expulsion through the rectum of a mixture of gases that are byproducts of the digestion process of mammals and other animals. The medical term for the mixture of gases is flatus, informally known as a fart, or simply gas...
) in the healthy adults, and an increase in nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
was seen in the HIV patients.
Intestinal effects
One of the most well-documented effects of L. reuteri is in the treatment of rotavirus
Rotavirus
Rotavirus is the most common cause of severe diarrhoea among infants and young children, and is one of several viruses that cause infections often called stomach flu, despite having no relation to influenza. It is a genus of double-stranded RNA virus in the family Reoviridae. By the age of five,...
-induced diarrhea, especially in children. Treatment of rotaviral diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
by consumption of L. reuteri significantly shortens the duration of the illness as compared to placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
. Furthermore, this effect is dose-dependent: the more L. reuteri consumed, the faster the diarrhea stops. L. reuteri is also effective as a prophylactic for this illness; children fed L. reuteri while healthy are less likely to fall ill with diarrhea in the first place. With regard to prevention of gut infections, comparative research has found L. reuteri to be more potent than other probiotic organisms .
L. reuteri is also an effective treatment against infant colic
Baby colic
Colic is a condition in which an otherwise healthy baby cries or displays symptoms of distress frequently and for extended periods, without any discernible reason...
. Over a period of several weeks, infants who are given L. reuteri steadily decrease the amount of time each day spent crying – the defining symptom of colic. In fact L. reuteri was much better in decreasing the infants' crying time than the standard therapy of simethicone
Simethicone
Simethicone is an oral anti-foaming agent used to reduce bloating, discomfort and pain caused by excess gas in the stomach or intestinal tract. It is a mixture of polydimethylsiloxane and silica gel.-Chemical action and pharmaceutical effects:...
treatment. A randomized, double-blind, placebo controlled trial of fifty exclusive breast fed colicky infants found a significant decrease in daily crying time amounts when treated with L. reuteri DSM 17 938 compared with placebo. It further found a significant increase in lactobacilli colonization, a decrease in fecal Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
and ammonia
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
when compared with placebo. However, colic is still poorly understood, and it is not clear why or through what mechanism L. reuteri ameliorates its symptoms. One theory of colic, though, holds that affected infants cry because of severe gastro-intestinal discomfort; if this is indeed the case, it is quite plausible that L. reuteri somehow acts to lessen this discomfort, since its primary residence is inside the gut.
There is conflicting evidence as to whether L. reuteri is capable of eradicating the gut pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
Helicobacter pylori
Helicobacter pylori
Helicobacter pylori , previously named Campylobacter pyloridis, is a Gram-negative, microaerophilic bacterium found in the stomach. It was identified in 1982 by Barry Marshall and Robin Warren, who found that it was present in patients with chronic gastritis and gastric ulcers, conditions that were...
, which causes peptic ulcers and is endemic in parts of the developing world. One study showed that dietary supplementation of L. reuteri alone reduces, but does not fully eradicate, H. pylori in the gut. Another study found that adding L. reuteri to omeprazole
Omeprazole
Omeprazole is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease , gastroesophageal reflux disease , laryngopharyngeal reflux and Zollinger–Ellison syndrome...
therapy dramatically increased (from 0% to 60%) the cure rate of H. pylori-infected patients compared to the drug alone. However, this result has since been contradicted by a follow-up study, which showed no benefit of adding L. reuteri to traditional antibiotic therapy for H. pylori eradication.
Oral health
L. reuteri may also be capable of promoting dental health, as it has been proven to kill Streptococcus mutans
Streptococcus mutans
Streptococcus mutans is a facultatively aerobic, Gram-positive coccus-shaped bacterium commonly found in the human oral cavity and is a significant contributor to tooth decay.The microbe was first described by J Kilian Clarke in 1924.-Introduction:...
, a bacterium responsible for tooth decay. A screen of several probiotic bacteria found that L. reuteri was the only species of those tested able to block S. mutans. Before testing in humans was begun, another study showed that L. reuteri had no harmful effects on teeth. Clinical trials have since proven that those people whose mouths are colonized with L. reuteri (via dietary supplementation) have significantly less of the harmful S. mutans. Since these studies have been short-term, it is not yet known whether L. reuteri prevents tooth decay. However, since L. reuteri is able to reduce the numbers of an important decay-causing bacterium, this would be expected.
Gingivitis
Gingivitis
Gingivitis is a term used to describe non-destructive periodontal disease. The most common form of gingivitis is in response to bacterial biofilms adherent to tooth surfaces, termed plaque-induced gingivitis, and is the most common form of periodontal disease...
also may be ameliorated by consumption of L. reuteri. Patients afflicted with severe gingivitis showed decreased gum
Gingiva
The gingiva , or gums, consists of the mucosal tissue that lies over the mandible and maxilla inside the mouth.-General description:...
bleeding, plaque
Dental plaque
Dental plaque is a biofilm, usually a pale yellow, that develops naturally on the teeth. Like any biofilm, dental plaque is formed by colonizing bacteria trying to attach themselves to a smooth surface...
formation, and other gingivitis-associated symptoms compared with placebo after chewing gum
Chewing gum
Chewing gum is a type of gum traditionally made of chicle, a natural latex product, or synthetic rubber known as polyisobutylene. For economical and quality reasons, many modern chewing gums use rubber instead of chicle...
containing L. reuteri.
General health
By protecting against many common infections, L. reuteri promotes overall wellness in both children and adults. Double-blind
Double-blind
A blind or blinded experiment is a scientific experiment where some of the people involved are prevented from knowing certain information that might lead to conscious or subconscious bias on their part, invalidating the results....
, randomized studies in child care centers have found that L. reuteri-fed infants fall sick less often, require fewer doctor visits, and are absent fewer days from the day care center compared to placebo and to the competing probiotic Bifidobacterium lactis.
Similar results have been found in adults; adults consuming L. reuteri daily end up falling ill 50% less often, as measured by their decrease use of sick leave.
Results in animal models
Scientific studies that require harming the subjects (for example, exposing them to a dangerous virusVirus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
) may obviously not be conducted in human
Human
Humans are the only living species in the Homo genus...
s. Therefore, many of the benefits of L. reuteri have been studied only in different animal species, such as pigs and mice
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...
. Given the similarity of mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian species, however, it is likely – though not scientifically proven – that these benefits hold true for humans as well.
In general, animal studies on L. reuteri are done using the species-specific strain of the bacterium (see above).
Protection against pathogens
L. reuteri confers a high level of resistance to the pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
Salmonella typhimurium, halving mortality rate
Mortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
s in mice. The same is true for chickens and turkeys; L. reuteri greatly moderates the morbidity and mortality caused by this dangerous food-bourne pathogen.
L. reuteri is also effective in stopping harmful strains of E. coli from affecting its host. A study performed in chickens showed that L. reuteri was as potent as the antibiotic gentamicin
Gentamicin
Gentamicin is an aminoglycoside antibiotic, used to treat many types of bacterial infections, particularly those caused by Gram-negative organisms. However, gentamicin is not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila...
in preventing E. coli-related deaths.
The protozoic parasite Cryptosporidium parvum
Cryptosporidium parvum
Cryptosporidium parvum is one of several protozoal species that cause cryptosporidiosis, a parasitic disease of the mammalian intestinal tract....
causes severe watery diarrhea, which can become life-threatening if the patient is immunocompromised
Immunodeficiency
Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...
(as in individuals infected with HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
). L. reuteri is known to lessen the symptoms of C. parvum in mice and pigs. Given that there is no known direct treatment for C. parvum (the antibiotic Paromomycin has limited effect), L. reuteri may prove valuable in protecting patients suffering from this disease.
Some protective effect against the yeast Candida albicans
Candida albicans
Candida albicans is a diploid fungus that grows both as yeast and filamentous cells and a causal agent of opportunistic oral and genital infections in humans. Systemic fungal infections including those by C...
has been found in mice, but in this case L. reuteri did not work as well as other probiotic organisms such as L. acidophilus and L. casei.
General health
In young commercial livestock
Livestock
Livestock refers to one or more domesticated animals raised in an agricultural setting to produce commodities such as food, fiber and labor. The term "livestock" as used in this article does not include poultry or farmed fish; however the inclusion of these, especially poultry, within the meaning...
such as turkey chicks and piglets, body weight
Body weight
The term body weight is used in daily English speech as well as in the contexts of biological and medical sciences to describe the mass of an organism's body. Body weight is measured in kilograms throughout the world, although in some countries it is still measured in pounds or stones and pounds...
and growth rate are good indicators of the health of the animal. Animals raised in the dirty, crowded environments of commercial farms
Factory farming
Factory farming is a term referring to the process of raising livestock in confinement at high stocking density, where a farm operates as a factory — a practice typical in industrial farming by agribusinesses. The main products of this industry are meat, milk and eggs for human consumption...
are generally less healthy (and therefore weigh less) than their counterparts born and bred in cleaner homes. In turkeys, for example, this phenomenon is known as "poult growth depression", or PGD.
Supplementing the diets of these young farm animals with L. reuteri helps them to largely overcome the stresses imposed by their unhealthy habitats. Commercial turkeys fed L. reuteri from birth had nearly a 10% higher adult body weight than their peers raised in the same conditions. A similar study on piglets showed that L. reuteri is at least as effective as synthetic antibiotics in improving body weight under crowded conditions .
The mechanism by which L. reuteri is able to support the healthy growth of these animals is not entirely understood. It is possible that L. reuteri simply serves to protect livestock against illness caused by Salmonella typhimurium and other pathogens (see above), which are much more common in crowded commercial farms. However, other studies have revealed that L. reuteri can also help when the growth depression is caused entirely by a lack of dietary protein
Protein in nutrition
Proteins are polymer chains made of amino acids linked together by peptide bonds. Proteins and carbohydrates contain 4 kcal per gram as opposed to lipids which contain 9 kcal per gram....
, and not by contagious disease. This raises the possibility that L. reuteri somehow improves the intestines' ability to absorb and process nutrient
Nutrient
A nutrient is a chemical that an organism needs to live and grow or a substance used in an organism's metabolism which must be taken in from its environment. They are used to build and repair tissues, regulate body processes and are converted to and used as energy...
s .
Effect on chemical and trauma-induced injury
Treating colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
ic tissue from rats with acetic acid
Acetic acid
Acetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...
causes an injury similar to the human condition ulcerative colitis
Ulcerative colitis
Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...
. Treating the injured tissue with L. reuteri immediately after removing the acid almost completely reverses any ill effects, leading to the possibility that L. reuteri may be beneficial in the treatment of human colitis patients.
In addition to its role in digestion
Digestion
Digestion is the mechanical and chemical breakdown of food into smaller components that are more easily absorbed into a blood stream, for instance. Digestion is a form of catabolism: a breakdown of large food molecules to smaller ones....
, the intestinal wall is also vital in preventing harmful bacteria, endotoxins, etc., from "leaking" into the bloodstream. This leaking, known as bacterial "translocation", is very dangerous and can lead to lethal conditions such as sepsis
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
. In humans, translocation is more likely to occur following such events as liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
injury and ingestion of some poison
Poison
In the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism....
s. In rodent studies, L. reuteri was found to greatly reduce the amount of bacterial translocation following either the surgical removal of the liver or injection with D-galactosamine
Galactosamine
Galactosamine is a hexosamine derived from galactose with the molecular formula C6H13NO5. This amino sugar is a constituent of some glycoprotein hormones such as follicle-stimulating hormone and luteinizing hormone...
, a chemical which also causes liver damage.
The anti-cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
drug methotrexate
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
causes severe enterocolitis
Enterocolitis
Enterocolitis is an inflammation of the colon and small intestine. However, most conditions are categorized as one or the other of the following:* Enteritis is the inflammation of the small intestine...
in high doses. L. reuteri greatly mitigates the symptoms of methotrexate-induced enterocolitis in rats, one of which is bacterial translocation.