Probiotics: live microbial supplements

Probiotics are live microbial supplements which are health promoting by virtue of their functional re-establishment and stabilization of microbial niche dynamics of the human gastro intestinal tract.

The bacteria population that inhabit the Gl tract have adapted such that their number of each genera are approximately constant with each their own growth niche. For the optimal function of intestines ,the dynamic balance of microflora has to be maintained. This has become increasingly difficult and unsustainable due to fast changing life styles.

Various facts shift the balance of gut flora away from potentially beneficial or health promoting microflora such as Lactobacillus acidophilus SP and bifidobacteria leading to a preponderance  of potentially harmful or pathogenic microbes like clostridia, sulphate reducers and certain bactericides species. The predominance of alter populations may predispose to a number of clinical disorders including colon cancer,inflammatory disorders, ulcerative colitis while subjecting the host more susceptible for infections by transient enteropaihogens like salmonella campylobacter , escherichia coli and listeria. It is of considerable benefit to the host therefore to maintain a good community structure through increased predominance of bacteria such as lactobacilli and bifidobacteria. In a recent review Benglark 1998 has highlighted the importance of microbial interference treatment as a means of infection control.

Though antibiotic therapy has solved some critical problems in life saving , it has also created new problems.

Increased awareness of the fact that antibiotic therapy deranges the protective flora there  by predisposing to several other infections is being increasingly realized now. An increase in antibiotic resistance microbial strains as a result of over prescription and or indiscriminate use of antibiotics is being seen today. There is also a growing fear that industry may not be able to develop effective antibiotics at such a sufficient rate to comply with the development of microbial resistance to old antibiotics.

Modern life styles vs natural  microbial dynamics
Modern life has been subjected to accelerated transitions of life styles in an unprecedented way hither to unknown in human evolution leading to resurgence of various conditions that have a profound impact on human health.

The gastrointestinal tract of human is a complex ecosystem with characteristics that depend at each moment on the dynamic equilibrium between host and the native bacteria (Abrams 1980).

As a result of altered lifestyle intestinal microflora gets modified. The intestinal flora modifies the morphology of the epithelial cells. One important role is its action on cell maturation observed in prayers patches. Resistance to pathogenic bacteria is conditioned by intestinal flora. The native flora ensures maintenance of the immune status by providing repeated antigen stimulation through out the life span.

The bacterial mass of the gut is itself an important sources for nutrients like Thiamine, Riboflavin, Folic cid, Vitamins B12,Pantothenic acid .Short chain fatty acids like acetic, butyric, valeric acids and proteins which are partially absorbed and used by the host thus serving as a nutrient source.

Types of biotics: Prebiotics
Prebiotic is a non- digestible food ingredient that beneficially affects the host by selective stimulation of growth and activity of one or limited number of bacterial in the colon that can improve host health (Gibsob and Roberfroid 1995).For e.g. Oliogosaccharides that contains fructose-Insulin.

Probiotics
Probiotics are live microbial supplements which beneficially affect the host by improvements of its intestinal microbial niche restoring balance . Eg. Lactobacillus sp and Bifidobacterium sp etc.

Symbiotics
Symbiotics are those with a mixture of both the above.

Desired characteristics of probiotics

• Non-pathogenic and non-toxic
• Withstand acidity in the stomach and bile salts later
• Adherence to intestinal mcosa
• Production of  enzymes and metobolities to maintain pH that  exerts beneficial affect on the host
•  Easy to culture and store

Selection of probiotics
Lactobacillus sp (acidophilus), Bifodobacterirn bifidium/ lactis are selected due to significant consumption with wide application and maket potential

Medical uses of probiotics

• Enhancement of bioavailability of vitamins and minerals by virtue of lowering of pH
• Nutrient source for vitamins like B complex vitamins and short chain fatty acids.
• By virtue of lowered pH in colon dr absorption is accelerated and enhanced.
• Lactose malabsorption: Half of the world population is unable to utilise lactose. Probiotics improve tolerance to lactose.
• Causes reduction in the production of bacterial enzymes in the faeces such as beta glucuronidases, sterols
• Alpha- dehdroxylase, Nitroredctases, Azoredctases that generate procarcinogens or carcinogens and tumour promoters. Amino acid metabolites are acted upon by tryptophanases on trytophane to produce indole, a known carcinogen. Para cresol is also produced by aerobic and anaerobic bacteria reacting with tyrosine. This complex event leads to a reduction of colon cancer.
• Improvement of peristaltic movements leading to alleviation of constipation.
• Inactivation of potential pathogens by competing with space as well as nutrients with perfect adhesion to mucosa.
• Causes reduction in the absorption of cholesterol thus warding off coronary heart diseases.*
• Causes immune stimulation/ modulation. The cell wall of LA mainly consists of peptidolglycons which are released during cell proliferation and cell death. This release is considered as a type of physiological response modifiers and are potent activators of the immune system (Human et al 1990)
• Inactivation of potential pathogens that the dynamics of ecology of gut flora. Enhanced antimicrobial activity against pathogens  is by Competitive Exclusion".
• Prevention of antibiotic associated diarrhoea, Rota virusdiarrhoeaea, reduced rota virus shedding adjuant activity and enhances phagocytosis.
• Reduced recurrence of superficial bladder cancer, prolonged survival and relapse free interval in cervical cancer, reduced infection in bacterial virginities.
• De-conjugation of bile acids thus reducing nitrosoamines.
• Obliteration of intestinal disorders in astronauts were successfully treated with Bifidobacterim.
• Synergistic augmentation of acceleration of drug absorption is influenced by !ocal ph. LA colonises ileum where lactose converted to glactose and glucose and the later is metabolized to lactic acid to cause pH to be near 5.3 to 5.6 where by drug absorption is augmented.
• Prevents colitis caused by clostridium difficale.

Human clinical studies & probiotics effect

• Lactose indigestion due to deficiency of beta galactosidase is improved by Lactobacillus acidophilus and Bifidobacterium.
• Rota virus diarrhoea, reduction of duration of diarrhoea. Enhanced immune response and reduced virus shedding by LA and Bifidobacterium.
• Reduced incidence of Travellers diarrhoea by LA.
• Immune modulation, induction of higher levels of immunoglobulin a secreting cells to rota virus in Rota virus infection. Adjuant activity and enhanced phagocytosis by Lactobacillus ( Gerriste et al 1990 , Fernandes et all 1987 Gillard 1990.
• Reduction of faecal enzyme activities eg: Glycocholic acid hydrolase, Beta Glucoronidase, nitroreductase, Azoreductase leads to reduction of carcionogens warding off colon cancer.
• Reduced recurrence of superficial bladder cancer by L.Casei.
• Prolonged survival and relapse-free interval L.Casei.
• Reduced reinfection in bacterial vaginitis by LA
• Women with post menopausal idiopathic osteoporosis have increased chance of lactic deficiency either due to reduced milk intake or secondary to intolerance to or impaired calcium absorption.
• LA flushing of pathogenic microbes from ileum by virtue of inhibitory factors released by LA and peristaltic action.
• LA Flushing of pathogenic microbes from ileum by virtue of inhibitory factors released by LA and peristaltic action.
• Thus, probiotics like LA and Bifidobacterium sp bestow beneficial effect on the host.

Probiotic role based on functions:
Adhesion to intestinal epithelium
This permits the formation of ecological niches with in which the bacteria is maintained regardless of the changes in the habitat thus enabling them to produce the genuine effect by forming a bacterial barrier which also acts as defence mechanism.

Action on morphology and physiology of  digestive tract well
Bifidobacteria influence the maturation and turnover cycle of the enterocyte together with the development of the intestinal velocities. They are also involved in the degradation and replacement of the intestinal mucins. They may also involved in the degradation and replacement of the intestinal mucins. They may also have action on the immune system appended to the digestive tract.

Nutritional effects
They produce vitamins like Bl, B6, B9, BI2 amino acids like alanine, valine~ aspartic acid and threonine. They produce only Lactic acid which is completely metabolized by man, enhances nutritional characteristics of the Bifidobacteria.

Metabolic effects
Bifidobacteria unlike Lactobacillus delbrueki ssp, bugaricus and Streptococcus salivarius ssp thermophilus are resistant to biosalts and as a result have a site in effect on the metabolism of lactose.

Hypercholesterolaemic effect
It has been demonstrated the correlation between lactic acid microtlora and a reduction in plasma cholesterol. Administration of very large quantities of bifidobacterium (109 bacteria per gram in fermented milk resulted in the fall of total cholesterol from 3.0 to 1.5 glm. Bacteria producing lactic acid also produce hydroxy methyl glutaryl - co -A reductase which is involved in the synthesis of cholesterol. It was conclusively proved in VITRO studies that bifidobacteria reduce cholesterol levels.

Deconjugation of bile acids
It helps in reduction of nltrosaminos and inhibition of the reduction of nitrates. The bile acids area secreted into the duodenum in the form of conjugates with glycine and taurine.

Any strains of Bifidobacterium hydrolyse Sodium glycolate and Taurocholate in the colon. The Hydrolases enzymes responsible are constitutive and extra­cellular.

Other metabolic effects
Ingestion of milk fermented with Lactobacillus acidophilus and Bifidobacterium bifidum for a period of three weeks has no effect on the production of hydrogen or methane or on foetal Beta glucosidase activity and these four parameters are good indicators of the fermentation capacity of colonic flora.

Barrier to pathogenic bacteria
Bifidobacteria have been shown to act as an anti-infectious barrier to pathogenic bacteria.

The following are some of the examples.

• B.longum has a barrier effect versus E. coli in the axenic rate.
• The intestinal flora on leukaemic patients is modified by chemotherapy and the bacteria which are usually rare in health state multiply considerably leading to disequilibrium of the intestinal micro flora which is countered by the oral administration of B.longum.
• Infants suffering from rota virus induces diarrhoea .The concomitant administration of B.longum fermented milk with antibiotic treatment results in reduction of number of stools, the number of bacteroids and also regain the weight compared with the treatment of antibiotics alone.

Therapeutic effect
Due to direct suppression of pro carcinogens produced by the bacterial enzymes,the host immune system is activated besides causing reduction in intestinal pH.

Prevention and treatment of other diseases
Digestive disorders like abdominal ballooning in diarrhoea or constipation in pregnant women is prevented by the administration of B.longum. Intestinal microflora is restored leading to the promotion of health.

The intestinal disorders in 34 Soviet Cosmonauts were successfully treated by Bifidobacteria.

The probiotic effect

• Prevention of the colonization of the intestines by pathogens by competing with the nutrients and for binding sites on the epithelial surfaces.
• Production of Lactic acid , acetic acid and other organic acids during the fermentation of carbohydrates with Bitidobacteria results in alternation of pH in the intestine leading to the inhibition of the growth of undesirable bacteria.

Acidification has a bactericidal potential especially versus gram negative bacteria. Acetic acid has strongest antagonistic effect versus gram negative bacteria than lactic acid. Acetic acid is produced by Bifidobacterium in larger quantities. The ratio between acetic acid and lactic acid is 3:2 which results in about 11 times more undissociated acetic acid than undissociated lactic acid. This acidity stimulates peristaltic movements of the intestines which facilitates the elimination of any pathogens present.

Implantation of Bifidobacteria is promoted in infants by breast feeding. The permanent acidity on the intestinal contents regulates the development of Bifidobacteria as a bacteriostatic effect versus E.coli and gram negative bacteria. B.longum has effect on humoral as well as cellular immunity.

Lactobacillus acidophilus and Bifobacterium bifidum constitute 80% of the global market.                                                 

- The author is founder ,former Director of Institute of Genetics, Hospital for Genetic Diseases,Osmania University