The beneficial effect of lactic acid bacteria on human's health is known since ancient times.
However, the particular interests in micro-organisms have rocketed at the end of nineteenth and early twentieth century.
In 1907, russian sciencist Ilya Mechnikow showed that consumption of feremented dairy products has a beneficial effect on human health by inhibiting the growh of pathogenic micro-organisms .
Attempts to use probiotics on a larger scale during this period failed, also intruduction of antibiotics made that probiotics forgotten for decades .
Back to the game
Widespread usage of antibiotics has produced number of strains resistant to them, with additional side effects of antibioticotheraphy.
After those times, the probiotics are coming back, stronger than ever before.
Nowdays sciencists increased their interests in microbiome as they started to understand how our small neighbours can influence our health.
There are trillions of microbes in human microbiome and they can weight approximately 1400g (3 pounds) and it appears that they impact our health and interestinglt the immune system .
In this article we will focus on health benefits of using probiotics, especially in the particular disesases.
What are the probiotics?
The term probiotic is nowdays used to name ingested microorganisms associated with health benefits for humans and animals .
However definition is likely to be changed, because of experimental results that show the beneficial effects of probiotic micro-organisms have also on dead bacteria, and even DNA isolated from bacteria .
Requirements for probiotics
The probiotics should :
- be originating from the gastrointestinal tract of healthy human body
- have the ability to live in the intestines and adhesion to intestinal cells and colonize the gastrointestinal tract
- not promote a gene transfer of antibiotic resistance
- show resistance to low pH gastric juices, bile and digestive enzymes
- not have the characteristics of pathogens
- have antagonistic activity in relation to pathogenic microorganisms , such as : Listeria monocytogenes , Salmonella , Clostridium difficile , Helicobacter pylori
- enhance nutrient absorption in the intestine and production of vitamins and enzymes
- survive in the process of freeze-drying at elevated temperatures and good development and ability to survive in the gut
- have the desired fermentation and enzymatic activity
How do probiotics work?
Although the precise mechanisms of action are not clarified yet. The suggested mechanisms include :
- modulation of GI (gastro-intestinal) immunity by altering the inflammatory cytokine profiles and breaking the proinflammatory cascascades
- displacement of gas-producing, bile saltt-deconjugating bacterial species and thus possibly inhibiting pathogenic bacterial adherence
- alteration of bacterial flora by acidification of the colon by nutrient fermenetation
- enhancement of epithelial barrier function
- induction of µ-opioid and cannabinoid receptors in intestinal epithelial cells
- reduction of visceral hypersensitivity, spinal afferent traffic and stress response
Proof of effectiveness
Probiotics have been a subject of research to examine whether the health claims made for them have any supporting evidence.
Although there is growing body of evidence that gut flora and humans have a mutualistic relationship, only little evidence supports claims that probiotic supplements provide health benefits especially in the long run.
The EFSA (European Food Safety Authority) has rejected all petitions for health claims on probiotic products im Europe due to insufficient evidence and thus inconclusive proof of effectiveness .
It is very difficult to demonstrate that probiotics are effective in supporting health. However recent developments of high-throughtput sequencing technology and the consquent progress of metagenomics reperesent a new approach for the future of probiotics research .
It is suggested that health improvement via the gut appears to be directly related to long-term dietary changes.
However usage of probiotics in particular health disorders have a strong scientific support and we will present it in this article, but let's first get to know some microbiological terms first.
What is a CFU?
Are you confused about reading about CFU on your container of probiotics? Not anymore!
CFU is a colony forming unit, and it is basically number of single bacterium (or yeast which has probiotics-like properties).
The reason of this term is if bacteria can form colonies and divide themselves – they are still alive and health.
What is an accurate dose?
Unfortunately, there is no simple answer for this question.
The recommended number of CFU depends of many different conditions.
Commercially available probiotic formulations typically have at least 106 CFUs, but they may range up to 1012 CFUs.
In general, the doses which can make any difference, as many experts say should be in billions (109) not millions (106), i.e. 5 billions of bacteria could be written as 5 x 109 CFU.
For the specific reference it is recommended to look at the doses used in the particular scientific studies related to ceratain health disorders.
Strain name is a must
If you want results, use probiotics that have their bacteria constituents (one or more) written as a full strain name i.e. „Lactobacillus rhamnosus GG” strain where the genus is Lactobacillus, the species is rhamnosus and the strain designation is GG.
Properties of probiotics are strain's dependent, therefore to use them consciously it is necessary to know the effects of particular strain, not only the type and/or species.
The results from effectiveness of particular strain in certain disease, should never be extrapolated on different even closely related strains.
For example, Lactobacillus reuteri RC-14 and Lactobacillus rhamnosus GR-1 are a combination particulary suited for the female urinary tract infections and using just the random multi strain probiotics will not give the same results .
Currently known probiotic species
- L. acidophilus
- L. amylovorus
- L. casei
- L. crispatus
- L. gasseri
- L. johnsonie
- L. paracasei
- L. plantarum
- L. reuteri
- L. rhamnosus
- B. adolescentis
- B. animalis
- B. lactis
- B. bifidum
- B. breve
- B. infantis
- B. longum
Bacteria and yeast which not produce a lactic acid
- Bacillus cereus var. toyoi
- Escherichia coli var. Nissle
- Propionibacterium freudenreichii
- Saccharomyces cerevisiae
- Saccharomyces boulardii
Other bacteria which produce a lactic acid
- Enterococcus faecium
- Leuconostoc mesenteroides
- Streptococcus thermophilus
Clostridium difficile infection
Clostridium difficile infection (CDI) is the main cause of antibiotic-associated diarrhea.
The incidence of CDI (and associated morbidity and mortality) worldwide has increased over the past decade .
Meta-analysis conducted by Farland has suggested that four probiotics (Saccharomyces boulardii, Lactobacillus casei DN114001, a mixture of L.acidiphilus and Bifidobacteriu bifidum, and a mixture of L. Acidophilus, L. Casei and L. Rhamnosus) significantly improved primary prevention of Clostriudium difficile infection .
Systematic review from 2013 which included 23 randomized controlled trials has shown that probiotics are both safe and effective for preventing Clostridium difficile-associated diarrhea (CDAD) .
Another meta-analysis results have shown that probiotics administration (Lactobacillus, Saccharomyces, and a mixture of probiotics were) was associated with significant reduction the risk of developing CDAD in patients receiving antibiotics .
Pediatric diarrhea is the most common cause of global mortality in children under five years of age .
Probiotics (Saccharomyces boulardii, L. rhamnosus GG, L. reuteri) are safe and effective in prevention of acute pediatric diarrhea.
The meta-analysis results have shown that duration of diarrhea was decreased by 13 hours, treatment failures by 38% and the risk of newcases of pediatric diarrhea to 43% .
The results from other three meta-analysis has also confirmed that probiotics decreased the duration of acute diarrhea in children by 20 (14-26), 17(7-29) and 30 (19-42) hours in comparison to placebo group .
Significant benefit in treatment of acute infectious diarrhea in infants and children was were noted by Szajewska and Mrukowicz, but also Ahmadi et al with usage of probiotics, particulary Lactobacillus GG strains [16, 17].
Studies on adults have also confirmed that probiotics, particulary S.boulardii can reduce the risk of and shortening the duration of persistent diarrhea [14,15].
The most common usage of probiotics is related to diarrhea and antibiotheraphy as a factor which can destroy the delicate balance of microbiota.
Many studies suggested that usage of S.boulardii, L. rhamnosus, L. casei, L. bulgaricus and thermophilus when taken parallely to antibiotic theraphy and for 1 week after completion of tratment, significantly reduce the risk of diarrhoea [14,15].
The most common recommendation of taking probiotics during the antibioticotheraphy is 1-2 hours after taking antibiotic, as a medicine will pass through the body and then you can safely replenish the good microflora .
The interesting can be a fact that S.boulardii is a yeast, so it is not affected by typical antibiotics used against bacteria, therefore no specific actions with parallel antibiotheraphy is required.
Ulcerative colitis (UC) is a chronic inflammatory disease, which etiology is unclear.
It has been suggested that genetic factors, immune response and gut microbiota may play key role in pathogenesis of this disorder.
Many studies have been shown that Eschericha coli Nissle 1917 (ECN) can be effective in treatment and inducing reemision of UC.
ECN is nonpathogenic, gram-negative strain, isolated in 1917 by Alfred Nissle and it is still use today (as a drug Mutaflor).
Administration of probiotic drug with ECN (200mg) in ulcerative colitis is as effective in inducing remission of disease as the gold standard - antinflammatory drug – mesalazine .
Other strain Lactobacillus GG in the dose of 18x109 CFU seems to be effective and safe for maintaining remission in patients with ulcerative colitis, and it could represent a good therapeutic option for preventing relapse in this group of patients .
Mardini and Grigoriani have undertaken meta-analysis which has shown that VSL#3 mix of probiotics, when added to conventional theraphy at a dose of 3.6 x 109 CFU daily is safe and more effective than conventional theraphy alone in achieving higher response and remission rates in mild to moderately active colitis ulcerosa .
There is is a strong evidence for use of probiotics in prevention and treatment of pouchitis (inflammation of the ileal pouch).
It has been suggested that bacteria play a primary role in patogenesis of pouchitis, causing inflamation .
It has been discovered that patients with pouchitis have fewer Lactobacilli and Bifidobacterium than healthy individuals .
Number of studies have shown that VSL#3 and LGG taken for 9-12 months in prevention and treatment of pouchitis can decrease the incidence and relapse of inflammatory response . The findings were limited to adults.
Irritable bowel syndrome
Irritable Bowel Syndrome (IBS) is a common chronic gastrointestinal disorder and the evidence suggest that pharmacotheraphy efficacy is low.
It can cause bouts of stomach cramps, bloating, diarrhea and/or constipation .
Popular alternative to drugs – probiotics have been researched as changes in microflora have been reported in patients with IBS .
IBS symptomps such as bloating or flatulence have been attributed to possilbe alterations in gut microflora and empirical introduction of probiotics .
Brenner et al have analyzed 16 RCTs (randomized-controlled trials) in IBS patients who received probiotics vs placebo.
One strain Bifidobacterium infantis 35624 demonstrated efficacy in two well designed RCTs.
Symptoms such as abdominal pain, bloating, incomplete evacuation, intestinal gas, straining and bowel function were significantly improved .
Some studies suggested the probiotics can be efficient in alleviating some of the sympthomps, but the magnitude of benefit and the most effective species and strains are uncertain [26, 29].
Central nervous system function and disorders
There are some promising data supporting the probiotics' usage in certain central nervous system disorders – including anxiety, depression, autism spectrum disorder, obsessive-compulsive disorders and improved certain aspect of memory.
The systematic review of 15 human randomized controlled trials, proved probiotics administration (B. longum, B.breve, B. infantis, L.helveticus, L rhamnosus, L.plantarum, and L.casei) that posses treatment efficacy in the above conditions .
Probiotics have been consumed by humans in one form or another for over 100 years, with a good safety record generally.
The above is true for immunocompetent hosts in an outpatient settings. However, probiotics intake by immunocompromised (HIV, cancer), chronically ill, hospitalized patients with GI disorders may lead to probiotic sepsis.
Specifically, in GI disorders accompanied by gut permability and when the gut immunity is compromised the administration of probiotics may increase bacteria translocation of bacteria into blood stream.
Until further studies on safety profile become available, caution with using them and healthcare professional advice is strongly recommended .
Side effects and interactions
Some of the probiotics, especially at the begining of administration can lead to excessive intestinal gas production and bloating.
If applicable, try to decrease the dose or use it every other day instead of every day .
Probiotics could interact with medicines such as antibiotics and immunosuppressive drugs so make sure, if that is the case, contact your health care provider prior to probiotics administration .
There are many uncertainties with probiotics usage such as recommended doses, duration of treatment, how long it takes to colonize, alter the microflora, and have impact on the immune.
This is why there is a need for further well-designed randomized-controlled trials.
The outcome of treatment depends of the strains of probiotics or combinations of strains used to address certain health disorders.
Only then, with adequate dose, health benefits and improvements can be achieved.
In the long run for maintaining the immune and digestive function, it appears that diet modifications might play the most important role to modify human host microbiome.
Currently there are few scientifically supported therapeutic uses of different strains: Saccharomyces boulardii, L. rhamnosus GG, L. reuteri in the acute diarrhoea, E.coli nissle 1917, LGG and VSL#3 in ulcerative colitis and pouchitis, S.boulardii, L. rhamnosus, L. casei, L. bulgaricus and thermophilus in antibiotic-associated diarrhoea.
The administration of probiotics aiming at central nervous disorders is very promising, but requires confirmation by further studies on larger populations.
Some of the data suggest that probiotics can be effective in alleviating IBS, especially Bifidobacterium infantis 35624, however there are a few question marks which have to be addressed in the future researches.
Probiotics are generally considered as safe, however extra caution and consultation with healthcare professional is mandatory when taken by immuno-compromised people (cancer, HIV), chronically ill, hospitalized patients and those with a risk of probiotics sepsis.
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