Probiotics:100 years (1907-2007) after Elie Metchnikoff

The scientific rationale for the use of live microbes in the prevention and treatment of infections came to lime-light most transparently at the beginning of the 20th century when Elie Metchnikoff in 1907 hypothesized that replacing or diminishing the number of ‘putrefactive’ bacteria in the gut with lactic acid bacteria could normalize bowel health and prolong life.

After more than half a century the term probiotics was coined to reflect Metchnikoff’s idea. It is now defined as ‘live microorganism, which when administered in adequate amounts confer a health benefit on the host’.

In the last 10 years, scientific research in probiotic microbiology has progressed considerably and significant advances have been made in the selection and characterization of specific probiotic cultures and substantiation of health claims relating to their use. Molecular and genetic studies have helped to uncover the mechanistic basis for the beneficial activities of probiotics.

It has taken one hundred years, but there are signs that Metchnikoff’s hypothesis is now truly being brought to life and many health attributes will indeed be conferred by use of probiotics.

Brief history of Elie Metchnikoff

Born on May 16, 1845 in Ukraine, Elie Metchnikoff studied natural sciences at the University of Kharkoff and pioneered research in immunology leading to the discovery of intercellular digestion in a flatworm.

In 1904, he became the deputy director at the Pasteur Institute laboratory in Paris from where he discovered the process of phagocytosis which demonstrated how specific white blood cells can break down harmful bacteria in the body. For this work, he was awarded the Nobel Prize for medicine in 1908.

Although there is reference to sour milk or fermented cultures as far back as the Bible, Elie Metchnikoff is regarded as the grand father of modern probiotics. He made a landmark observation that the regular consumption of lactic acid bacteria in fermented dairy products, such as yogurt, was associated with enhanced health and longevity in Bulgarian peasant populations.

He linked this to the ‘Bulgarian bacillus’ which was discovered by a 27-year old Bulgarian physician Stamen Grigorov, and he later demonstrated how healthy bacteria in yogurt helped digestion and improved the immune system. The scientific rationale for the health benefit of lactic acid bacteria was provided in his book “The prolongation of life” published in 1907.

He asserted that some of the bacterial organisms present in the large intestine were a source of ‘toxicants’, toxic substances that contributed to illness and aging. He 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" [1].

To test the hypothesis on the health benefit of consuming lactic acid bacteria, Metchnikoff drank sour milk every day until his demise at the ripe age of 71 years in 1916.

Historical development of Probiotics.
At the time of Metchnikoff’s scientific demonstration of lactic acid bacteria benefits, Henry Tissier, a French paediatrician, working independently observed that children with diarrhea 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 [2]. He suggested that these bacteria could be administered to patients with diarrhoea to help restore a healthy gut flora.

The pre and post-world war discovery of antibiotics may have triggered abandoning Metchnikoff’s concept, as apart from the launch of Yakult in Japan in the 1930s, and ongoing studies in the Soviet Union, there is little evidence to indicate that Metchnikoff’s concept was taken seriously, at least from a commercial standpoint. Indeed, between 1908 and 1964, little or nothing was heard of microbial therapy in Western countries.

In 1965, the term ‘probiotics’ was first used by Lilly and Stillwell [3] in a different context to represent ‘substances secreted by one organism which stimulate the growth of another’. After nine years, Parker [4] described probiotics as “organisms and substances which contribute to intestinal microbial balance”.Fifteen years later, Fuller [5] proposed that probiotics were ‘live microbial supplements which beneficially affects the host animal by improving its microbial balance.

This was followed by Salminen et al., [6] who defined probiotics as ‘foods containing live bacteria which are beneficial to health’. As research in probiotics become more visible and in confirming the validity of evidence on probiotics, the United Nations Food and Agriculture Organization and the World Health Organization (FAO/WHO) in 2001, sponsored an Expert Consultation following a request from the Argentinian government. During the consultation which was chaired by Dr. Gregor Reid, the Director of the Canadian Research and Development Centre for Probiotics, a consensus definition of probiotics was adopted as “live microorganisms which when administered in adequate amounts confer a health benefit on the host” [7].

This is now the widely used and accepted definition as it embraces all applications of live microbes, not just those for intestinal benefits. Probiotics beyond fermented dairy products Many microbial types are used around the world to ferment milk, plant food, meat and other products.

Two of the most widely known and characterized are Lactobacillus delbreuckii subsp. bulgaricus and Streptococcus thermophilus. They were reported to positively influence the microbiota of the gastrointestinal tract, thereby decreasing toxic microbial metabolic activities [8]. However, much progress has been made since in terms of the fermentation of dairy products. In this regard most probiotics fall into categories of lactic acid-producing bacterial organisms, including Lactobacillus and Bifidobacterium, but also non-lactic acid organisms.

Probiotics are most often incorporated in yogurt and fermented milk, but other food lines are now available and numerous products are sold in tablet, capsule, and powder forms. The dairy version require refrigeration in the distribution channels, outlets and homes (unless the products are eaten within a day of purchase), and these may not always be available.

Some dried formulations, can survive without refrigeration, as long as they are retained in proper vials with appropriate desiccants, and kept in a cool, dry location suitable for the developing countries with tropical temperatures [9].

EXCERPTS FROM Paper by: Kingsley C. Anukam 1,2∗ PhD, MHPM and Gregor Reid 1,2,3 PhD, MBA, ARM, CCM

1 Canadian Research and Development Centre for Probiotics, Lawson Health Research Institute, 268 Grosvenor Street, London, Ontario, N6A 4V2, Canada.
2 Department of Microbiology & Immunology, University of Western Ontario, Canada. 3 3 Department of Surgery, University of Western Ontario, Canada.

Posted: Feb 3 2011