Probiotics : Should We Consider it in Therapeutics ?

Probiotics are receiving increasing attention in the medical field. This is partly due to the recognition that microbial resistance to antibiotics presents a serious world-wide problem. In addition, fast growing insight into host-microbe interactions opened new routes in the development of rational alternatives in therapy and prevention of diseases as result of the complex procaryotic-eucaryotic evolutionary symphony. Consequently, long existing aspects of probiotics came into focus, and already provide exciting prospects. DOI: http://dx.doi.org/10.3329/jom.v13i1.10049 JOM 2012; 13(1): 55-59

penetration across this barrier, serving as a link between inflammatory diseases of the gut and systemic inflammatory disorders. 1,3But the host friendly microflora play crucial role to fight against the offending organisms via different ways: • Strengthening the epithelial barrier, thereby preventing translocation of pathogenic bacteria.
• Competing with pathogenic bacteria for attachment to epithelial cells.
• Creating a local environment that is unfavorable for the growth of many pathogens.
• Enhancing the mucosal immune response to pathogens.

How the micro population of the intestine is affected?
There is a progressive increase in immune-mediated, gutrelated health problems such as allergies and autoimmune and inflammatory diseases in modern society. 2 Many factors are theorized to contribute to a disruption of healthy bacterial balance and a decline in host defense mechanisms in the gut.These include medications such as gastric acid inhibitors or neutralizers, high fat/low fiber diets, and contaminated food and water.But perhaps the most prevalent cause of indigenous microflora disruption is the widespread and chronic use of antibiotics. 4,5Because antibiotics do not distinguish between pathogenic and healthful bacteria, they can severely disrupt intestinal and urogenital microbial balance.Suppression of the indigenous microflora may lead to reduced colonization resistance and overgrowth of preexisting, naturally resistant microorganisms, such as Clostridium difficile, which may cause diarrhea and/or colitis. 4For example, a recent study found that after a course of antibiotics, patients were 3 times as likely to report functional bowel complaints 4 months after treatment compared with patients who did not receive antibiotics. 6dditionally, by altering the microflora of the vagina, antibiotics can increase a woman's propensity for urinary tract infections (UTIs) and vaginal candidiasis. 7New colonization by resistant pathogens may also occur, thus promoting the emergence and spread of antibiotic resistant strains. 5The injudicious overuse and misuse of antibiotics has led to a global emergence of antibiotic resistance.To illustrate, 70% of bacteria that cause hospital-acquired infections are resistant to at least one commonly used antibiotic, and some organisms are resistant to all approved antibiotics and must be treated with experimental drugs with potential toxicity. 8mmunity-acquired antibiotic resistance is also a growing problem, as evidenced by the fact that in some communities up to 40% of Streptococcus pneumoniae strains are now resistant to penicillin. 9Additionally, there is an increasing prevalence of resistance to several antibiotics used to treat UTIs. 10 A well-balanced intestinal microflora reduces the risk of infections in the gut and urogenital tract, and thus is an important factor in reducing the need for antibiotics.Furthermore, a healthy microflora can prevent establishment of resistant strains.In this context, it is easy to see that if the microflora balance and colonization resistance of the host could be maintained at a healthy, normal level, the risk of emergence and spread of resistant strains could be mitigated.This may be accomplished through the therapeutic application of beneficial microorganisms, or probiotics.

Probiotics selection criteria
The criteria for a microorganism to be defined as a probiotic include that the strain be of human origin, be safe for human use, be stable in acid and bile, and adhere to the intestinal mucosa. 21,33,34The genera most frequently used as probiotics are Lactobacillus and Bifidobacterium.While many lactobacilli strains are available for human use, relatively few have substantial scientific evidence that supports their effectiveness. 21,34,35Furthermore, many questions have been raised about reliability, viable content, and the general quality of many probiotic products.The properties that are important in selecting a strain of lactobacilli include the ability to adhere to the intestinal mucosa, resist acid and bile, and produce antimicrobial substances.

Intestinal Adherence
The ability to adhere to the intestinal mucosa is a critical selection criteria because adhesion is considered to be a prerequisite for colonization. 17Adhesion is also considered important for stimulation of the immune system.The stomach and upper intestinal tract represent a hostile environment that can easily discourage growth or survival of microorganisms.Although many lactobacilli survive selective pressures of this environment, flow rates of digesta through the small intestine would wash out any organism unable either to multiply rapidly enough to avoid dilution or to maintain their residence by physical attachment to the intestinal epithelium. 36

Acid and Bile Tolerance
To survive passage through the stomach and upper small intestine, probiotic strains must be able to tolerate the acidic and protease-rich environment of the stomach, and survive in the presence of bile acids. 33Bile tolerance is considered to be an important characteristic of L. acidophilus that enables it to survive, grow, and exert its action in the lower small intestine and colon. 31,33,37

Antimicrobial Activity
The ability to competitively exclude or inhibit pathogenic intestinal bacteria through antimicrobial action is a major benefit attributed to L. acidophilus, and is an important consideration when selecting strains. 38These substances include growth-inhibiting metabolites such as organic acids and hydrogen peroxide, as well as bacteriocins, adhesion inhibitors, and a range of small antimicrobial substances. 33

Clinical Evidence of health benefits
Numerous studies have confirmed the many wide-ranging beneficial effects of probiotics, such as improving intestinal tract health, enhancing the immune system, and reducing symptoms of lactose intolerance.In addition, evidence is emerging that potential benefits of probiotics may include treatment and prevention of allergies and inflammatory diseases, cancer prevention, and a reduction in respiratory disease.Several of these clinical benefits are discussed below.

Anti-Carcinogenicity
There is considerable interest in the role of the intestinal microflora in colon carcinogenesis 12,16,19 and other forms of cancer. 25,39Bacterial metabolism of various dietary constituents results in the production of many compounds, some of which may be carcinogenic.Altering the composition of the intestinal flora with probiotics may have a major effect on the production rate of these compounds.Indeed, epidemiological studies indicate a correlation between regular consumption of fermented dairy products and low incidence of colon cancer. 12,19,25,39Several studies have measured the activities of microbial enzymes that play a role in the conversion of procarcinogens to carcinogens, including glucuronidase, nitroreductase, and azoreductase. 19,25,26,39all Bowel Bacterial Overgrowth Patients with chronic kidney disease often suffer from small bowel bacterial overgrowth (SBBO), which is accompanied by production of toxic amines such as dimethylamine (DMA). 17,28The researchers found that Probiotics changed small bowel pathobiology by modifying metabolic actions of SBBO, reducing generation of toxins and carcinogens with no adverse side effects.

Immune Function
Approximately 70% of the immune system is localized in the GI tract and the intestinal mucosa provides a protective host defense against the constant presence of antigens from food and microorganisms. 3,40The intestinal microflora provides important support for this defense barrier, as shown by increased antigen transport across the gut mucosa in its absence. 40In addition to strengthening the intestine's permeability barrier, probiotics have been shown to enhance immune responses, particularly immunoglobulin A, and thereby promote the intestine's immunologicbarrier.
Probiotics have also been shown to stimulate non-specific host resistance to microbial pathogens and to control the balance of proinflammatory and antiinflammatory cytokines. 40herefore, in addition to strengthening the intestinal barrier, probiotics may down-regulate hypersensitivity reactions and hold promise in the prevention and treatment of conditions associated with gut barrier dysfunction and sustained inflammatory responses, such as inflammatory bowel disease.

Assimilation of Cholesterol
It has been reported that L. acidophilus may play a role in reduced serum cholesterol levels in humans and animals.31,32Certain strains of L. acidophilus, have the ability in vitro to assimilate cholesterol from a laboratory growth medium, although with wide variation. 32,35Such assimilation of cholesterol in the small intestine may be important in reducing the absorption of dietary cholesterol from the digestive system into the blood. 31,32e Health benefits of Bifidobacteria Bifidobacteria is another probiotic naturally occurring in humans, with Bifidobacterium infantis being the dominant microorganism to colonize the intestines of breast-fed newborns.Research studies have documented several beneficial effects of bifidobacteria when given to infants, such as its effectiveness against a specific strain of enteropathogenic E. coli, in prevention of enteric infections, and in decreasing the growth of C. albicans. 14,18,41Recent research into the immune-enhancing effectiveness of bifidobacteria in the elderly also shows great promise.The researchers suggest that supplementation of bifidobacteriain the elderly may be a natural, non-invasive way to resist the decline in cellular immunity associated with the aging process.Acids produced by bifidobacteria include short-chain fatty acids (SCFAs) such as acetic, propionic, and butyric acids, as well as lactic and formic acids. 41,42These acids have an antimicrobial effect by lowering the pH of the colon, in addition to other inhibitory influences on bacterial cell growth.The most plentiful SCFA produced by bifidobacteria is acetic acid, which exerts a wide range of antimicrobial activity against yeasts and molds as well as bacteria.

Conclusion:
Old age, antibiotics and other medications, and immunocompromised states can all contribute to a disruption of the indigenous microflora population, putting patients at increased risk for infection and disease.The use of probiotics offers an intervention with essentially no risk that may provide significant health benefits by stabilizing the intestinal microflora.When choosing a probiotic, it is important to select strains that fulfill the criteria that are required for establishment in the intestinal tract and have demonstrated clinical effectiveness.