Key Historical Moments For Medicinal Microbes

Exploring the History of Probiotics

By Tess Deyett, PhD (Co-founder of Microbigals) and Philippe Rolshausen, PhD

In the past half decade probiotics have exploded onto the market claiming to cure everything from depression to obesity. Every major nutritional company has come out with new microbial products to “benefit” your health. And although it may seem microbes are newly discovered gold mines of limitless potential, these little microbial helpers have been impacting, shaping, and driving human history long before we knew of their existence. 

Microbes were the first living organisms on this planet, arising some 3,400 million years ago (mya). To put this into perspective, the lineage of humans arose only 10 mya. It took some 9,999,600 years of human evolution before Antonie van Leeuwenhoek first peered down the microscope, revealing for the first time microscopic life. It was the first truly groundbreaking event that burst open the field of microbiology, but not our first understanding of beneficial microbes.

Bulgarian Yogurt, Source: Wikimedia Commons - author: Ned Jelyaxkov

Before probiotics were a pill, they were natural inhabitants of fermented foods, like yogurt, sauerkraut and kefir. The process of fermentation is carried out by busy little microbes. Like commercial probiotics pills of today, fermented food has also seen a surge in popularity due to their health benefits such as reducing risk of high blood pressure, diabetes, obesity and inflammation. 

Fermented foods have claimed a spot in our history as far back as the Egyptian’s hieroglyphs. In the 15th century, Suleiman the Magnificent’s (1494-1566) prescribed yogurt to Francis I of France (1494-1547) for his severe diarrhea. In addition to healthy microbes, these foods contain a high amount of ethanol, organic acids and bacteriocins which are all antimicrobials, preventing microbial growth. Humanity tried to harness the power of beneficial microbes long before they knew what they were.

Elie Metchnikoff, Souce: Wikimedia Commons - credit: Wellcome Images

Elie Metchnikoff was one of the first people to champion microbes as medicine. In a time when people were trying to sterilize the colon (going as far as surgically removing it) because it was a “vestigial cesspool”, Metchnikoff was prescribing sour milk produced by certain lactic bacteria. He was so committed to this belief, he himself made yogurt a regular part of his diet, concluding rather unscientifically, he was “very well pleased with the result.” 

In 1907, Elie Metchnikoff, published his book called the “The prolongation of life” after his key observation that Bulagrian peasants who regularly consumed yogurt seemed to live longer and healthier lives. The strain in the yogurt became known as the “Bulgarian bacilli” and Elie Metchnikoff became known as the ‘father of probiotics.’ 

During the same time period, Tissier, a French pediatrician, observed that children with diarrhea had lower counts of a ‘Y’ shaped bacteria, which he called ‘bifid’ bacterium, and concluded these organisms could be given to the sick children to aid in their recovery. Bifidobacterium is one of the most researched probiotics today. It’s very likely if you are taking probiotics, they include at least one species of Bifidobacterium.

By WWI, Dr. Aldred Nissile discovered a strain of Escherichia coli that was antagonistic to Salmonella (a common ailment of  soldiers). He coined the term “antagonistic activity” and created the “antagonistic index” to determine how effective a strain of E. coli was to destroy Salmonella cells. 

Micrograph of L. casei strain Shirota

On the other side of the world, In 1935, the Japanese microbiologist, Minoru Shirota, was the first to commercialize probiotics with his drink, Yakult. Shirota’s probiotic drink includes a bacterial strain which he isolated known as Lactobacillus casei strain shirota. If you’ve never tried Yakult head down to your local grocery store, I bet you’ll find it! 

During WWII, a great scientific discovery occurred that forever revolutionized modern medicine and completely abolished interest in probiotic research. This of course was penicillin, which has a fascinating story. Antibiotics are quick and effective. They destroy a pathogen, eliminating it from the host almost immediately. Unfortunately, they also eliminate many other good bacteria.

Probiotics And Prebiotics...So Human Focused

So while the warring years put a stop to a lot of probiotic research, there was a resurgence in the 1950s. In 1953, we got the first official use of the word ‘probiotic’ coined by Kollath. ‘Pro’ meaning ‘for’ in latin and ‘βιοτος’ the greek word for ‘life.

Source: Wikimedia Commons - author: Helen Spence-Jones

By the 1980s, antibiotic resistance, increase in cost, and limited pharmaceutical research, sparked new interest in the field of probiotics. It was not until 2001, that the Food and Agriculture Organization (FAO) of the United Nations and the World Health Organization (WHO) officially defined probiotics as: ‘live organisms which when administered in adequate amounts confer a health benefit on the host’.  

Closely related to probiotics is the concept of prebiotics. In 1995, the concept for prebiotics was first proposed by Gibson and Roberfroid, and Roberfroid later defined prebiotic as: “a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confer benefits upon host well-being and health”. 

Criteria for prebiotics include (i) resistance to the acid in the gut (must survive)  (ii) ability to be fermented (eaten) by gut microbes and (iii) it must promote the growth or health of beneficial microbes in the gut. 

In the early studies of antibiotics, scientists discovered that by supplementing lab animal diets with folic acid (a prebiotic) the adverse effects of antibiotics were reduced. Furthermore, lactulose, a well-known prebiotic for Lactobacilli, was commonly found in infant formula dating back to the 1950s.

Today, research in the microbiome, the natural microbial residents of a site, has exploded, showing that microbes are implicated in nearly all aspects of host health, from humans to plants. The microbiome is a vast interconnected complex community that incorporates all three kingdoms of life, adapted specifically to the host. In return for nutrients and protection, the microbiome assists the host in digestion of foods, synthesis of vitamins, competes against pathogens, assisting in protection from infection. When you take a probiotic, this is the community you are trying to optimize. A probiotic is gentrification of your gut.  

Probiotics And Prebiotics For Agriculture

The terminology of probiotics and prebiotics in agriculture is fairly new, however; the concept of amending soil to promote plant health is not. Stemming from the human definition, a plant prebiotic would be an exogenous product that stimulates the microbe’s, producing a benefit to the plant. Likewise, a plant probiotic would be a living microbe or microbial community that when applied, interacts with the plant and provides a health or crop yield benefit (aka, plant growth promoting bacteria). 

Although probiotics and prebiotics to plants have never been defined, they have been researched as far back as the late 19th century. The first patent of a bioinoculant was granted to Nobbe and Hilten in 1896 for a pure culture of rhizobia and commercialized under the product name “Nitragin”. Biopesticides have been used in agriculture to control plant diseases for over a century. Bt toxin, a toxin produced by the Bacillus thuringiensis, was the first biopesticide to control plant pests and is still broadly used in agriculture today. In addition, the EPA registered in 1979 its first biocontrol, Agrobacterium radiobacter K84, to control crown gall.

Plant Microbiome, Souce: Wikimedia Commons - authors: Murali Gopal & Alka Gupta

Similar with humans, the plant probiotic field dwindled with the innovation of powerful microbial killers. For plants it was pesticides. But we are beginning to see this change as a broad spectrum of microbes are being used commercially in agriculture to control diseases or improve plant health. The benefits of using such organisms may be enhanced when multiple microbes are mixed, a concept known as biofertilizers. 

In addition, prebiotics have been used since the ancient times in the form of compost to stimulate microbial communities by enriching soil organic matter. Today, products like Biochar are used for similar purposes. Biochar is the conversion of plant or animal biomass into a solid carbon rich material that is able to retain nutrients and water while fostering the growth of microorganisms. These substances can replenish soils with nutrients, increase crop productivity and yield. 

The Future of Probiotics

It has been estimated that $20 billion is spent on spreading 2.5 million tons of pesticides annually worldwide. Those resources are largely deployed to manage plant diseases that account for $40 billion in crop loss annually. On the human side, although antibiotics save countless lives, 30% of all antibiotics prescribed are unnecessary. 

This is an almost incomprehensible amount that has severe effects on our world by increasing multi-drug resistance microbes, greenhouse gas emission, and water contamination while depleting soil health, and straining our medical system.

Public health and environmental pollution, off target effects, high productivity costs and rise in pathogen resistance has exacerbated the need for an alternative approach. The field of probiotics and prebiotics may be young but it is filled with limitless opportunities. Opportunities to not only understand the world around us but to provide healthy and natural solutions to both human and agriculture problems, especially in a time where sustaining the growing population is of utmost concern.