Good bacteria for good life

With the global market for probiotic products showing good growth, therapeutic usage is also slowly gaining acceptance in the Indian market. Sushmi Dey finds out what research is being done

‘Daily piyo, healthy jiyo,’ the jingle might sound like that of any other health drink but this time it is all about a drink that contains live micro organisms. 'Probiotics' is the more commonly used word for it. The concept has come a long way from making probiotic drinks and yoghurts popular with catchy punch lines to using probiotics in making drugs for serious diseases like diarrhoea, periodontal diseases and inflammatory bowel diseases. No wonder, the Rs 120 crore probiotic drug market, growing at about 40 percent per annum in India, is attracting pharmacos who want to get first mover advantage. While new insights into the benefits offered by probiotics are boosting the market still further, major research driven pharmacos like Alkem Laboratories, Dr Reddy's Laboratories (DRL), Glenmark, and Ranbaxy Laboratories are taking interest in the science behind probiotics.

Good bacteria

"Probiotics might theoretically cause infections that need to be treated with antibiotics, especially in people with underlying health conditions" - Dr Sharad Kasarle Vice President R&D Nutraceuticals Alkem Laboratories

The human digestive tract is home to over 400 species of microorganisms, of which some are good ones while others are harmful to our body. Probiotics is the answer to keep the harmful ones at bay. According to the definition adopted by WHO, probiotics are "live microorganisms which when administered in adequate amounts confer a health benefit on the host." In simpler words, probiotics are new generation biotechnology drugs and dietary supplements developed from yeast or lactic acid bacteria. According to Dr Sharad Kasarle, Vice President, R&D Nutraceuticals, Alkem Laboratories, in most cases probiotics are bacteria.

These bacteria are similar to those naturally found in people's guts, especially in breastfed infants, which allow them natural protection against many diseases. Most often, the bacteria come from two groups, Lactobacillus or Bifidobacterium. Within each group, there are different species and within each species there are different strains or varieties.

Apart from bacteria, there are also a few common probiotics in the form of yeasts. For instance, Saccharomyces boulardii is a yeast and is different from bacteria.

Probiotic bacteria are resistant to gastric, bile and pancreatic juices and hence reach the intestines alive in large numbers, whereas on reaching the acidic environment of the stomach, most ingested live bacteria die due to gastric acid. "A good probiotic agent needs to be non-pathogenic and non-toxic, resistant to gastric acid and bile and must reach the intestines alive in large numbers. It should transiently grow in the gut and impart health benefits to the host," says Dr Neerja Hajela, Head-Science Activities, Yakult India.

For good health

"It is critical to understand that any probiotic food or drug has to have a bare minimum quantity of bacteria to be effective" - Kanwaljeet S Chadha Country Head CD Pharma India

Probiotic drugs are designed to replenish the good bacteria in our guts and help improve microbial balance within patients' body. Experts suggest that probiotic bacteria belong to the natural flora with low or no pathogenicity and show functions that are important for the health and well-being of the host.

Of more than 100 trillion bacteria present in the human gut, it is important to ensure that the beneficial bacteria in the gut outnumber harmful ones. "Probiotics have a tendency to grow in the intestines where they increase number of beneficial bacteria and inhibit growth of harmful bacteria thus maintaining a balance between beneficial and harmful bacteria," says Hajela.

When illness, use of antibiotics, stress, irregular diet etc disrupt the natural balance and harmful bacteria increases in number, it results in diseases and ill health. "Consumption of probiotics as a part of daily diet helps to regulate the level of beneficial bacteria and reinforces the barrier against harmful pathogenic organisms. Their regular intake helps improve digestion, maintain immunity and prevent infections—the key to a long disease free life," suggests Hajela.

Therapeutic usage

Since the last decade there is a spread of awareness about the beneficial effects of probiotics. While experts say that additional controlled studies are required to clearly define safety and efficacy, probiotics have demonstrated an ability to prevent and treat a variety of conditions and infections.

Effective use of probiotics could decrease patients' exposure to antimicrobials. "Probiotics normally prevent proliferation of pathogenic bacteria in the gut. So whenever they are suspected to be deficient or whenever massive infection of the gut with pathogenic bacteria is suspected, probiotics are administered to counter the balance in favour of probiotics or healthful bacteria," says Rakesh Tandon, Head-Department of Gastroenterology, Pushpawati Singhania Research Institute for Liver, Renal and Digestive Diseases. No wonder, the use of probiotics as therapeutic agents for gastrointestinal disorders is rapidly moving into clinical usage. For instance, probiotics is useful in treating antibiotic induced diarrhoea or infectious diarrhoea, travellers' diarrhoea, infantile diarrhoea, constipation, Salmonella and Shigella infections, lactose intolerance and flatulence.

There is also encouraging evidence for the use of probiotics to prevent and treat infections of the urinary tract or female genital tract. Probiotics are also useful in treating irritable bowel syndrome and inflammatory bowel diseases like ulcerative colitis and Crohn's disease. According to Kasarle, probiotics can also treat infection with Helicobacter pylori, a bacterium that causes most ulcers and many types of chronic stomach inflammation.

Studies carried out over the years have shown that probiotics can treat dental problems such as periodontitis, gingivitis and halitosis. Recently, US-based VSL Pharma announced the introduction of its patented probiotic drug 'Inersan' to address the problem of weak gums in India. The drug is to be marketed by Ranbaxy Laboratories. "Periodontitis, gingivitis and halitosis are common dental problems which if ignored can lead to more serious complications. Dental practitioners in India currently do not have any specialised prescription product for these conditions and Inersan tablets address this need for the segment," says Sanjeev Dani, Senior Vice President and Regional Director Asia and CIS, Ranbaxy Laboratories. Periodontitis is a gum disease which in early stages is painful and causes swollen and bleeding gums. If left untreated, the disease can lead to serious infection and eventually may cause tooth loss. Though the problem might not look bigger, studies depict that gum diseases can affect a person's overall health. For instance, cardiac ailment patients should be more careful to avoid periodontitis since the bacteria from the mouth can cause clotting problems in the cardiovascular system and increase the risk of heart attacks.

Interestingly, recent tests conducted by scientists at UK-based University of Ulster suggest that probiotic drugs/drinks could also help reduce cancer progression or recurrence of cancer as the bacteria have an anti-cancer effect in the bowel which limits the build up of genetic damage in cells and stops them from growing out of control.

Probiotics are increasingly preferred over antibiotics by doctors. Reason being, antibiotics reduce the immunity of patients, whereas probiotics help enhance immunity. "There are cells in the digestive tract connected with the immune system. If you alter the microorganisms in a person's intestinal tract by introducing probiotic bacteria, you can affect the immune system's defences," explains Kasarle.

With all their proven therapeutic effects, can probiotics replace drugs? According to Tandon, probiotics can have therapeutic benefits but are not drugs. "Probiotics are living micro organisms that are consumed in order to obtain a beneficial effect regardless of their intrinsic nutritional value. They can be operationally described as commensal organisms that can be harnessed for therapeutic benefit but they are not drugs," asserts Tandon.

Side effects

Although, probiotics' safety has not been thoroughly studied scientifically, experts say that some live microorganisms have a long history of use as probiotics without causing illness in people. However, more information is required, especially on how safe probiotics are for young children, elderly people, and people with compromised immune systems. "Immuno-suppressed persons may develop systemic infection from the probiotic bacteria given orally. So in that group and among the elderly, one should be careful in using probiotics," suggests Tandon.

However, according to Kasarle, side effects due to probiotics, if they occur at all, tend to be mild and digestive. "Probiotics might theoretically cause infections that need to be treated with antibiotics, especially in people with underlying health conditions. They could also cause unhealthy metabolic activities, too much stimulation of the immune system, or gene transfer," says Kasarle.

Moving ahead

However, with more encouraging evidence from studies of specific probiotic formulations, use of probiotics is rapidly moving towards clinical usage. Experts say that scientific studies are providing mechanisms of action to explain therapeutic effects, and randomised controlled trials are providing necessary evidence for their incorporation into the therapeutic armamentarium. However, not all individual probiotic strains have the same efficacy and future clinical trials may focus on multi-strain preparations agents with known efficacy. According to Kasarle, there is research going on to use probiotics to treat immuno-deficient disorders such as Human Immuno-deficiency Virus (HIV), cancer and some chronic disorders such as tuberculosis. Vaginal infection is also another area of research for probiotics efficacy. "There are studies going on to control the exacerbation of ulcerative colitis and the other to see its efficacy in microscopic colitis," informs Tandon.

Recent reports suggest that apart from gastrology-related drugs, new probiotic drugs are being developed in areas like paediatrics, oral care and gynaecology.

Promising Indian market

Probiotic related functional foods have already captured the Indian market with strong players like Yakult, Amul, Nestle and Mother Dairy launching innovative probiotic products like drinks, ice creams, sweeteners, ready-to-eat cookies and jellies with health claims. On the other hand, big pharmacos like DRL, Glenmark, CD Pharma (a wholly owned subsidiary of VSL Pharma) and Alkem have already launched drugs with these bugs. At present there exist over 40 probiotic drug brands in India of which a majority are in the area of gastroenterology.

Further, the market is expected to grow exponentially. "India has a huge market for probiotics because of the large number of people suffering from acute diarrhoeal diseases," says Tandon. Many major Indian pharmacos are also in the process of developing and in-licensing probiotic drugs. After launching Inersan with Ranbaxy, VSL is also in talks with another big pharmaco to license its lead drug VSL-3 used to treat irritable bowel syndrome that causes abdominal pain, gas, diarrhoea and constipation.

"We intend to introduce products to treat problems of uterus, kidney, and skin and are talking to various Indian drug makers. Ranbaxy would distribute our product for gum related problems 'Inersan' in India and Nepal," says K S Chadha, Country Head, CD Pharma India.

There are also other probiotic drugs like Enterogermina (from Sanofi-Aventis), ViBact (USV), Darolac (Aristo), Pre-Pro (Fourrts), Bifilac (Tablet India), Sporlac (Uni-Sankyo), Prowel and Sporotic (Alkem) and Econorm and Becelac (DRL) available in the Indian market and enjoying huge market share. Alkem also manufactures Fructo-oligo saccharides which helps the growth of good probiotic bacteria.

Need for awareness

However, industry experts feel that there is a lack of complete understanding of probiotics in India. "In India people are becoming increasingly aware of natural ways to good health and as the awareness about the benefits of probiotic foods increases more and more people will start consuming them as a part of their daily diet," opines Hajela. Chadha agrees, "Probiotics is a new concept in India and is yet to be completely understood. Medical education is needed to create awareness about probiotics."

The industry also feels that there is a crying need for regulatory guidelines for use of probiotics. "Specificities of the bacteria and their doses need to be established," says Tandon. Experts say that it should be recommended that all manufacturers declare the strain of probiotic bacteria used and number of bacteria present. This is an accepted norm globally, and in India too it will go a long way to help the consumer make an informed choice. "It is critical to understand that any probiotic food or drug has to have a bare minimum quantity of bacteria to be effective," says Chadha.

Besides, in India there are no separate regulations dealing with dietary supplements, health food supplements and nutraceuticals. Currently, in India products are classified as food or drug under law. "New legislation governing the labelling of probiotics, such as indicating the species, strain and number of bacteria present is likely to come into force in the near future. These specific regulations for the evaluation of probiotics in food will enable the consumer to make an informed choice," opines Hajela. Indian Council of Medical Research (ICMR) is also forming a task force committee to work to form guidelines for the use of probiotics. According to Dr Sujit Kumar Bhattacharya, Additional Director General of ICMR, Department of Biotechnology (DBT) is also working on regulatory guidelines for use of probiotics and ICMR may join DBT on the job.

Probiotics has progressed from home-grown products to global brands and today the consumer has variety and health within reach. As research leads the market, this is surely one arena where the good will always win over the bad.

sushmi.dey@expressindia.com