The discovery of probiotics and their role in health – Myth or reality?

The human body hosts trillions of microorganisms that live alongside it. Half of these microorganisms are accounted for by the community of bacteria, fungi, protozoa and viruses known as the microbiota. Considering the microorganisms in the microbiota together with their genes is referred to as the microbiome.

Research on the microbiota increased rapidly after the Human Microbiome Project began, and its effects on our health are too significant to ignore.

The microbiota is unique to each person, like a fingerprint

Its formation begins in the womb, and its diversity changes throughout life. It is affected by many factors, including mode of birth, diet, age, sex, antibiotic use, genetic predisposition, geographical location and disease. Through metabolites released by the gut microbiota (for example, short-chain fatty acids), which affect systems throughout the human body, particularly the immune system, it behaves like an endocrine organ.

Dysbiosis: Disruption of the balance of bacteria in the gut microbiota

In conditions such as obesity, diabetes, cancer and Alzhemier, the microbiota differs according to the disease. However, it is inappropriate to blame a single bacterial species, because microorganisms live in communities with complex, reciprocal relationships.

The search for ways to manipulate the microbiota

Because the microbiota interacts with systems in the human body, efforts are being made to develop ways to manipulate it. Examples include the use of probiotic and prebiotic products, Fecal Microbial Transplantation (FMT), medicines and potentially vaccines in the future. This article discusses the emergence of probiotics and how they were commercialized.

The history of probiotics

Towards the end of the 19th century, Louis Pasteur discovered the fermentation properties of lactic acid bacteria and described them as beneficial bacteria because they prevented food spoilage. The discovery that not all bacteria are harmful marked a turning point in science. Élie Metchnikoff, who received the Nobel Prize in 1908 for his work on phagocytosis, proposed a hypothesis linking macular degeneration (yellow spot disease) to the gut microbiota. He believed that the bacteria in the gut could determine our fate. His hypothesis was that if lactate produced by bacteria during fermentation could inhibit the growth of harmful bacteria, the same process could occur in the gut. Consequently, lactic acid bacteria could inhibit toxin production in the gut. Today, Lactobacillus bulgaricus and Streptococcus thermophilus bacteria are used to produce yogurt.

Metchnikoff worked to isolate pure cultures from a sample of Bulgarian fermented milk containing these bacteria. In doing so, he discovered probiotic bacteria and their importance.

Isaac Carasso, a businessman of Greek origin, was deeply affected by seeing the impact of malnutrition (inadequate nutrition) and disease on Spanish children during World War 1. Exactly 102 years ago, inspired by Metchnikoff’s work on dairy cultures, he mixed fresh milk through trial and error with bacteria capable of fermentation that had been isolated at the Pasteur Institute, to produce what are now Danone yogurts. This was the birth of commercial ready-made yogurt.

He gave his first yogurt the nickname “Little Daniel,” after his son Daniel. This ready-made yogurt was initially sold in porcelain containers in the city’s pharmacies for its health-promoting effects (see the photograph below). After 5 years, the Barcelona College of Physicians visited, the product received praise, and its main marketing channels were expanded beyond pharmacies to reach more consumers. Ten years later, Daniel joined the family business, and the company adopted its present name, Danone. While Danone was expanding successfully across France, the outbreak of World War 2 prompted its move to the United States.

During these years, yogurt continued to be consumed as a healthy food. Because of fermentation, its content of vitamins B2, B6 and B12, calcium, potassium, zinc and magnesium is higher than that of other dairy products. The breakdown of lactose in yogurt by enzymes found in L. bulgaricus and S. thermophilus lowers lactose levels and makes dairy products easier to consume for people with lactose intolerance. In the 20th century, building on Pasteur’s legacy, scientists isolated other health-promoting strains, such as Escherichia coli, Lactobacillus acidophilus LB and Lactobacillus casei Shirota.

A definition of probiotics emerges

In 1974, Richard B. Parker proposed defining probiotics as “organisms and substances that contribute to the microbial balance of the intestine”. In 2001, the World Health Organization (DSÖ) published the definition “live microorganisms that provide a health benefit to humans when administered in adequate amounts”. Lactobacillus, Bifidobacterium, Streptococcus and Bacillus bacteria, and Saccharomyces, Aspergillus and Candida yeasts, are known as probiotics.

Danone began producing two probiotic fermented milk products: Activia® containing Bifidobacterium lactis (BFMP) in 1987, and Actimel® containing L. casei (LFMP) in 1994.

The potential health benefits of probiotics are being investigated

In the 1990s, a research program was launched to establish the benefits of probiotics, resulting in more than 40 scientific publications. The benefits of probiotic products range from reductions in the incidence or duration of digestive complaints, intestinal transit, common infections and diseases, and respiratory and gastrointestinal infections to the prevention of diarrhea resulting from antibiotic use.

Results relating to BFMP use have been associated with improvements in gastrointestinal complaints, and reduced symptoms have been reported in people with inflammatory bowel disease.

The birth of modern microbiology ushered in a new era. Modern metagenomic studies have made it possible to examine the mechanisms of action of bacteria in the microbiome. Laboratory consortia in Europe and the United States paved the way for research through MetaHIT and the Human Microbiome Project. Danone Nutricia Research participated in the MetaHIT study. Focusing on gut health, it collaborated with universities such as the Harvard T.H. Chan School of Public Health, UCLA and Washington University on a probiotic product containing Bifidobacterium lactis.

Research supports the hypothesis that BFMP benefits health by influencing the activity of the gut microbiome and components of the gut–brain axis. Evidence has been found that BFMP stimulates pathways leading to the production of beneficial short-chain fatty acids (KZYA) in the gut microbiome and reduces intestinal gas production. Results from different studies of the gut–brain axis have given rise to the idea that this product reduces visceral hypersensitivity and regulates brain activity.

It was recognized that not all study participants responded to BFMP in the same way, meaning that individuals could be affected differently by the same probiotics. Recently, the reduction in intestinal gas production associated with BFMP has been observed only in people who release large amounts of hydrogen.

Evidence has been found for two types of microbiota: permissive and resistant. A permissive microbiome is more susceptible to the effects of BFMP than a resistant microbiome. These results have paved the way for an era of "precision probiotics”.

Precision probiotics will perform gut functions that are not provided by the gut microbiome. They will be tailored to an individual’s diet, phenotype, lifestyle, age, sex, genetics and microbiome. The first precision probiotics are L. bulgaricus and S. thermophilus, the bacteria used in yogurt fermentation.

Probiotics may consist of traditional lactic acid bacteria, as well as Bifidobacterum and Akkermansia Municiphi. Akkermensia is a bacterium isolated from the gut that shows promise in metabolic health. Research shows that it improves various metabolic parameters in people who are obese or overweight.

In 2013, Danone Nutricia Research and collaborators at UCLA published the first probiotic clinical study of the gut–brain axis, showing that four weeks of BFMP intake by healthy women affected activity in brain regions controlling the processing of emotions and sensations. This suggests potential benefits of probiotics beyond the gut, including effects on the brain and the cardiovascular, metabolic, bone, muscle and immune systems.

A partnership was established with the University of California to understand the best ways to nourish the gut microbiome. By launching The Human Diets and Microbiome Initiative (THDMI), the partners aim to discover the best diets and foods consumed around the world that could benefit the gut. Future research focuses on a mechanistic understanding of the benefits of probiotics. Such understanding would affect not only gut health but many aspects of health, from the neurological to the immune system and from pediatrics to geriatrics. However, the gut microbiota is a complex system, and although most products on the market in this area are weakly supported by scientific evidence, they have reached a large market volume.