LACTIC ACID BACILLI
PHARMACOLOGICAL ACTION:
From a physiological point oF view Lacto bacilli antagonize the growth of non-acidogenic
intestinal bacteria, either saprophytes (whicH are usual guests in the intestine) or
pathogenic bacteria. Then "action is topical and is mainly influenced by lactic acid, which
is produced in substanlial amounts, and by other inhibiting metabolites (Antagonizers β’
bacteriocines).
~
Among the various Lactobacilli, Lactic Acid Oacillus ranks very high in the production
Of dextro rotatary,L(+), Laclic acid. When ingested, beFore or afler meal, spores of LacticAcid Bacillus cross the gastric acidity of stomach (in stomach ACTIVATION of spores takes place) and bile of duodenum (in duodenum GERMINATION of spore takes place)
practically undamaged. When they reach the intestine, germinated spores are transformed into "vegetative cells** Which are metabolically very active. Once established in intestine,they multiply quickly and through a massive production of L(+) Lactic acid(Dextrorotatary) and certain inhibiting metabolities.They slay in the intestine for about 7 days after discontinuation of administration and do not settle permanently. Tills semi-resident nature of Lactic Acid Bacillus Powder is more desirable one when it is used as a drug. During the period of administration,the acid intestinal environment favours the growth of the indigenous lacto bacilli typical of the ecosystem and stabilish or reinforce begin microbial processes (GUBIOSIS) that improve the health. Thus. withoul causing any pathological and pharmaceutical side effects (he Lactic Acid Bacillus Powder has prophylactic and therapeutic activities against dirrhoea, dyspepsia, constipation, abnormal intestinal Fermentation and nutritional disturbances.
Toxicity :
None
Contraindications :
None
After effects :
None
Precautions :
None
Drug interactions :
None
History ofProbiotics
The term probiotic is a relatively new word meaning "for life" and it is currently used to name bacteria associated with beneficial effects for humans and animals. The original observation of the positive role played by some selected bacteria is attributed to Eli Metchnikoff, the Russian born Nobel Prize recipient working at the Pasteur Institute at the beginning of the last century, who suggested that "The dependence of the intestinal microbes on the food makes it possible to adopt measures to modify the flora in our bodies and to replace the harmful microbes by useful microbes" (Metchnikoff, 1907).
At this time Henry Tissier, a French paediatrician, observed that children with diarrhoea had in their stools a low number of bacteria characterized by a peculiar, Y shaped morphology. These "bifid" bacteria were, on the contrary, abundant in healthy children (Tissier,! 996). He suggested that these bacteria could be administered to patients with diarrhoea to help restore a healthy gut flora.
The works of Metchnikoff and Tissier were the first to make scientific suggestions about the probiotic use of bacteria, even if the word "probiotic" was not coined until 1960, to name substances produced by microorganisms which promoted the growth of other microorganisms (Lilly and Stillwell, 1965). Fuller (1989), in order to point out the microbial nature of probiotics, redefined the word as "Alive microbial feed supplement which beneficially affects the host animal by improving its intestinal balance". A quite similar definition was proposed by Havenaarand Huis in 'tVeld (1992) "a viable mono or mixed culture of bacteria which, when applied to animal or man, beneficially affects the host by improving the properties of the indigenous flora".
A more recent, but probably not the last definition is "live microorganisms, which when consumed in adequate amounts, confer a health effect on the host" (Guarner and Schaafsma, 1 998). In the last 20 years, however, research in the probiotic area has progressed considerably and significant advances have been made in the selection and characterisation of specific probiotic cultures and substantiation of health claims relating to their consumption.
Members of the genera Lactobacillus and Bifidobacterium are mainly used as probiotic microorganisms. Some ecological considerations on the gut flora are necessary to understand the relevance of the probiotic conceptfor human health.
Bacteria are normal inhabitants of humans (as well as the bodies of upper animals and insects) including the gastrointestinal tract, where more than 400 bacterial species are found (reviewed by Tannock, 1 999): half of the wet weight of colonic material is due to bacterial cells whose numbers exceed by 10-fold the number of tissue cells forming the human body. Normally the stomach contains few bacteria (103 colony forming units per ml of gastric juice) whereas the bacterial concentration increases throughout the gut resulting in a final concentration in the colon of 10 bacteria/g. Bacterial colonisation of the gut begins at birth, as new-borns are maintained in a sterile status until the delivery begins, and continues throughout life, with notable age-specific changes (Mitsuoka, 1992). Bacteria, forming the so-called resident intestinal microflora, do not normally have any acute adverse effects and some of them have been shown to be necessary for maintaining the well-being of their host.
As an example of the beneficial role of intestinal microflora, it is possible to cite what has been referred to as "colonization resistance" or "barrier effect" (van der Waaij et al., 1 971; Vollaard and Clasener, 1 994) meaning the mechanism used by bacteria already present in the gut to maintain their presence in this environment and to avoid colonization of the same intestinal sites by freshly ingested microorganisms, including pathogens. Therefore, it could be assumed that dietary manipulation of gut microflora, in order to increase the relative numbers of "beneficial bacteria" could contribute to the well being of the host. This was also the original assumption of Metchnikoff who however, cautioned that:"Systematic investigations should be made on the relation of gut microbes to precocious old age, and on the influence of diets which prevent intestinal putrefaction in prolonging life and maintaining the forces of the body." This prudent statement can still be regarded today as an invitation to scientists to investigate the probiotic bacteria in more depth and with care.
Guidelines for the Assessment of Probiotic Microorganisms
In order to assess the properties of pro-biotics, the Consultation suggested that the following guidelines be used. For use in foods, pro--biotic microorganisms should not only be capable of surviving passage through the digestive tract but also have the capability to proliferate in the gut. This means they must be resistant to gastric juices and be able to grow in the presence of bile under conditions in the intestines, or be consumed in a food vehicle that allows them to survive passage through the stomach and exposure to bile. They are Gram positive bacteria and are included primarily in two genera, Lactobacillus and Bifidobacterium (Holzapel et al., 1998; Klein et al., 1998).
Selection of probiotic strains for human use
Probiotics must be able to exert their benefits on the host through growth and/or activity in the human body (Collins et al., 1 998; Morelli, 2000). However, it is the specificity of the action, not the source of the microorganism that is important. Indeed, it is very difficult to confirm the source of a microorganism. Infants are born with none of these bacteria in the intestine, and the origin of the intestinal microflora has not been fully elucidated. It is the ability to remain viable at the target site and to be effective that should be verified for each potentially probiotic strain.
Use of probiotics m otherwise healthy people
Many probiotic products are used by consumers who regard themselves as being otherwise healthy. They do so on the assumption that probiotics can retain their health and well-being, and potentially reduce their long-term risk of diseases of the bowel, kidney, respiratory tract and heart. Several points need to be made on this assumption and its implications. The Consultation recognized that the use of probiotics should not replace a healthy lifestyle and balanced diet in otherwise healthy people.
Firstly, there is no precise measure of "health" and subjects may actually have underlying and undetectable diseases at any given time. Secondly, no studies have yet been undertaken which analyse whether or not probiotic intake on a regular basis helps retain life-long "health" over and above dietary, exercise and other lifestyle measures. One study of day care centres in Finland showed that probiotic use reduced the incidence of respiratory infections and days absent due to ill health (Hatakka et al., 2001). The Consultation would like studies to be done to give credibility tothe perception that probiotics should be taken on a regular basis by healthy men, women and children. Such studies should be multi-centred and require randomization on the basis of age, gender, race, nutritional intake, education, socio-economic status and other parameters.
It is currently unclear as to the impact of regular probiotic intake on the intestinal microflora. For example, does it lead to the depletion or loss of commensal microorganisms which otherwise have beneficial effects on the host? While there is no indication of such effects, the issue needs to be considered. Furthermore, the concept of restoring a normal balance assumes that we know what the normal situation in any given intestinal tract comprises. It was deemed important by the Consultation to further study the various contributions of gut microorganisms on health and disease. Another point worthy of note is that, to date, the ingestion of probiotic strains has not led to measurable long-term colonization and survival in the host. Invariably, the microorganisms are retained for days or weeks, but no longer (Tannock et al., 2000). Thus, use of probiotics likely confers more transient than long-term effects, and so continued intake appears to be required.
In newborn children, where a commensal flora has not yet been established, it is feasible that probiotic microorganisms could become primary colonizers that remain long-term, perhaps even for life. While such probiotic usage can prevent death and serious morbidity in premature, low birth weight infants (Hoyos, 1 997), the alteration of flora in healthy babies is a more, complex situation. Just so, an implication of the Human Genome Project is that selected probiotics may be used at birth to create a flora that improves life-long health. These issues are very importantforthe future, and will require full discussion including human ethical considerations.
With respect to measuring the health benefits in human studies, consideration should be given to clinically relevant outcomes in the population being studied. For diarrheal studies, this might be preventing death in some countries, while in others it might be prevention of a defined and statistically significant weight loss, decreased duration of watery\liquid stools, and faster recovery to normal health, as measured by restoration of normal bowel function and stool consistency.
Although it is known that certain probiotics can elicit beneficial effects, little is known about the molecular mechanisms of the benefits reported (Andersson etal., 2001). The mechanisms may vary from one probiotic to another (for the same benefit via different means) and the mechanism may be a combination of events, thus making this a very difficult and complex area. It could involve the production of a specific enzyme(s) or metabolite(s) that act directly on the microorganism(s), or the probiotic could also cause the body to produce the beneficial action.
Examples of possible probiotic mechanisms of action, in the control of intestinal pathogens include:
β’ Antimicrobial substance production
β’ Competitive exclusion of pathogen binding
β’ Competition for nutrients
β’ Modulation of the immune system
The Consultation proposes that clear experiments (in vitro and/or in vivo) should be designed at the molecular level to elucidate the mechanisms of probiotic beneficial effects. Appropriate experiments including genetic analysis to elucidate the mechanism of actions should be performed.
Probiotic bacteria containing a-galactosidase can be added to food to improve lactose maldigestion (Kim and Gilliland, 1 983). However, a similar health effect is also observed for lactose fermenting starter bacteria such as L. delbrueckii. ssp. bulgaricus and S. thermophilus in fermented milk products like yogurt (Kim and Gilliland, 1 984; Kolars et al., 1 984). These traditional starters are not considered probiotics since they lack the ability to proliferate in the intestine (Klein et al., 1998).
Safety Considerations
Antimicrobial resistance profiles ofprobiotics
As with any bacteria, antibiotic resistance exists among some lactic acid bacteria, including probiotic microorganisms (Salminen et al., 1 998). This resistance may be related to chromosomal, transposon or plasmid located genes. However, insufficient information is available on situations in which these genetic elements could be mobilized and it is not known if situations could arise where this would become a clinical problem.
There is concern over the use in foods of probiotic bacteria that contain specific drug resistance genes. Bacteria, which contain transmissible drug resistance genes, should not be used in foods.
Currently, no standardized phenotypic methods are available which are internationally recognized for lactobacilli and bifidobacteria (non-pathogens). The Consultation recognizes the need for the development of standardized assays for the determination of drug insensitivity or resistance profiles in lactobacilli and bifidobacteria.
The Consultation is aware that pldsmids exist in lactobacilli and bifidobacteria, especially in strains isolated from the intestine, which have genes encoding antibiotic resistance. Due to the relevance of this problem, it is suggested that further research be done relating to the antibiotic resistance of lactobacilli and bifidobacteria.
When dealing with selection of probiotic strains, it is recommended that probiotic bacteria should not harbour transmissible drug resistance genes encoding resistance to clinically used drugs. Research is required relating to the antibiotic resistance of lactobacilli and bifidobacteria and the potential for transmission of genetic elements to other intestinal and/or food borne microorganisms.
Safety of probiotics in humans
In terms of safety of probiotics, the Consultation believes that a set of general principles and practical criteria need to be generated to provide guidelines as to how any given potential probiotic microorganism can be tested and proven to have a low risk of inducing or being associated with the etiology of disease, versus conferring a significant health benefit when administered to humans. These guidelines should recognize that some species may require more vigorous assessment than others. In this respect, the evaluation of safety will require at least some studies to be performed in humans, and should address aspects of the proposed end use of the probiotic strain.
Information acquired to date shows that lactobacilli have a long history of use as probiotics without established risk to humans, and this remains the best proof of their safety (Naidu et al., 1999; Saxelin et al., 1 996). Also, no pathogenic or virulence properties have been found for lactobacilli, bifidobacteria or lactococci (Aguirre and Collins, 1993). Having stated that, the Consultation acknowledges that under certain conditions, some lactobacilli strains have been associated with adverse effects, such as rare cases of bacteremia (Saxelin et al., 1996). However, a recent epidemiological study of systematically collected lactobacilli bacteremia case reports in one country has shown that there is no increased incidence or frequency of bacteremia with increased usage of probiotic lactobacilli (Salminen etal., 2001).
It is also acknowledged that some members of lactic acid bacteria, such as enterococci may possess virulence characteristics. For this and other reasons, the Consultation recommends that Enterococcus not be referred to as a probiotic for human use. The rationale is based upon:
A. Strains can display a high level of resistance to vancomycin (Shlaes et al., 1989; Eaton and Gasson, 2001; Lund and Ediund, 2001), or can acquire such resistance. If this resistance is present, transfer to other microorganisms may occur and this could enhance the pathogenesis of such recipients (Nobleetal., 1 992; Leclercq and Courvalin, 1997).B. Certain strains of vancomycin resistant enterococci are commonly associated with nosocomial infections in hospitals (Leclercq and Courvalin, 1 997; Woodford etal., 1 995).
The Consultation recognizes that some strains of Enterococcus display probiotic properties, and may not at the point of inclusion in a product display vancomycin resistance. However, the onus is on the producer to prove that any given strain cannot acquire or transfer vancomycin resistance or be virulent and induce infection.
Prebiotics
Prebiotics as an area is distinct from probiotics and therefore, will not be covered in detail in this report. The Consultation recognizes both the potential benefits of prebiotics with respect to probiotics, in addition to their ability to stimulate indigenous beneficial bacteria in the host. Prebiotics are generally defined as 'nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacterial species already established in the colon, and thus in effect improve host health1 (Gibson and Roberfroid, 1995).
The concept of prebiotics essentially has the same aim as probiotics, which is to improve host health via modulation of the intestinal flora, although by a different mechanism. However, there are some cases in which prebiotics may be beneficial for the probiotic, especially with regard to bifidobacteria, that is the synbiotic concept. Synbiotics are defined as 'mixtures of probiotics and prebiotics that beneficially affect the host by improving the survival and implantation of live microbial dietary supplements in the gastrointestinal tract of the host1 (Andersson et al., 2001).
Conclusions
1. Adequate scientific evidence exists to indicate that there is potential for the derivation of health benefits from consuming food containing probiotics.
2. There is good evidence that specific strains of probiotics are safe for human and able to confer some health benefits on the host.
3. The health benefits for which probiotics can be applied include conditions such as gastrointestinal infections, certain bowel disorders, allergy, and urogenital infections, which afflict a large portion of the world's population. The application of probiotics to prevent and treat these disorders should be more widely considered by the medical community.
4. In addition, there is emerging evidence to indicate that probiotics can be taken by otherwise healthy people as a means to prevent certain diseases and modulate host immunity.