Probiotics: History, Science and Genetic Sequencing

In the world of wellness and healthy eating, fads come and go, but some things live beyond the trends. Take probiotics, for instance. 

Probiotics are live bacteria and yeasts that provide our bodies with a myriad of benefits. For many of us, we first became aware of probiotics through the celebrity-endorsed yogurt commercials of the ’80s and ’90s, which famously touted how they’d make you “regular.” 

In more recent years, the fermented tea drink known as kombucha has become a wildly popular beverage among Americans, as well as the yogurt drink kefir, both of which are rich in good bacteria. Of course, you can always get probiotics in capsule or sachet form. 

It’s clear that probiotics are here to stay, but where did they come from? Probiotics are, in fact, about as old as civilization itself. Let’s explore the history of probiotics as we know them, and how our understanding of them has continued to evolve today.

The History of Fermentation

The history of probiotics walks hand-in-hand with that of humankind. And while we didn’t always understand probiotics the way we do in the modern era, we’ve been consuming them for centuries, thanks to fermentation.

Fermentation is a chemical process in which the enzymes of microorganisms break down sugars in a food or drink. This enzymatic process creates new compounds such as ethanol, lactic acid, and carbon dioxide that add different tastes and textures to the food. 

For instance, the yeast in bread dough uses fermentation to harness energy from the glucose in flour, creating CO2 as a waste product and resulting in bubbles that help the dough rise when baked. This change in composition also occurs in cheese, as lactic acid creates that distinctly appealing flavor and aroma.

Probiotics in Ancient Times

People have been fermenting their food and drink for over 10,000 years to preserve and improve flavor, aroma, and texture. Nearly every civilization has its own series of methods: archeologists have discovered records of fermentation in neolithic China circa 7000 B.C., where drinks made of fermented rice were especially common. In the Bible’s Genesis (18:1-8), Abraham is said to have brought offerings of “veal, bread, and sour milk,” suggesting the acidic flavor created by lactic acid in fermented dairy products. It has also been said that the Prophet Muhammad gave the mountaineers of Caucasus kefir, a fermented drink rich in lactic acid.

Fermentation was also practiced by the Sumerians, who were among the first people to farm for food. In ancient cuneiform texts from around 1800 B.C., there are records of cereals being delivered to breweries and even hymns singing the praises of brewing beer. Records also show that Sumerians fermented milk: in one farmer’s account, it’s mentioned that he had excellent returns the previous year in milk, butter, and cheese from his cattle.

Ancient Egyptians were also known to ferment food, especially through the baking of sourdough bread. Bread was a staple of every Egyptian’s diet, as demonstrated by the many records from tombs and temples portraying the process of gathering and processing grains to mill the flour for the bread. This flour would be used for the dough and the starter culture, which is naturally made from yeasts in the air. This culture would help the dough rise before the loaves were baked, resulting in an airy, chewy texture with lots of flavor.

Perhaps most impressively of all: the world’s oldest cheese was found on a mummy from 1615, B.C. in the Taklamakan desert of China. 

Still, the wonders behind fermentation weren’t truly discovered until the 20th century.

The Discovery of Probiotics

Probiotics were first scientifically documented in 1907 when Russian scientist and Nobel Prize winner Élie Metchnikoff researched the inhabitants of Bulgaria’s Caucasus Mountains. He was fascinated by the high ratio of centenarians (people who live to be 100 or older) in the area and observed that the villagers in the region regularly drank a type of fermented yogurt. 

As a contemporary of Louis Pasteur, who identified the microorganisms instrumental in fermentation, Metchnikoff was interested in the effect such microorganisms had on human health. As a result, he was quick to study the microbes he might find in the yogurt these villagers drank.

After studying the microbes under a microscope, he discovered that this yogurt contained a type of bacteria which he identified as Lactobacillus bulgaricus, a microorganism that had recently been discovered by the Bulgarian physician Stamen Grigorov. And as we know today, the culturing of milk for yogurt is typically accomplished by adding lactic acid bacteria such as Lactobacillus bulgaricus and Streptococcus thermophilus.

When this connection was made, Metchnikoff’s research suggested that Lactobacilli might counteract the negative GI impacts that contributed to illness and aging. Metchnikoff referred to Lactobacilli as “probiotics,” which originates from the Latin term “pro,” meaning “for,” and the Greek word “bios” or “biotic,” meaning “life.” 

Today, we know that probiotics are found in many different bacterial and yeast genera, but Metchnikoff’s findings served as the foundation of what we know about probiotics. For instance, modern research shows benefits from probiotics like boosting mood, easing digestion issues, and supporting healthy immunity.

If it weren’t for this discovery, our understanding of probiotics wouldn’t have evolved the way it has in the past century. Here is what our understanding of probiotics looks like today as a result of Metchnikoff’s legacy.

Probiotics in Modern Times

Probiotics are more prevalent in our society than ever before, and it’s apparent with the increasingly popular fermented foods like kombucha, yogurt, and kimchi. However, modern-day probiotics have to do with a lot more than tasty food. Probiotic research has advanced with the easy availability of whole genome sequencing in recent decades.

Probiotics & Genetic Sequencing

Genetic sequencing is the process of determining the order of the four chemical “building blocks” known as bases, which make up the DNA molecule. These bases include adenine, guanine, cytosine, and thymine, and they tell scientists the type of genetic information carried in a specific DNA segment. This is incredibly valuable in the case of probiotics, because it’s helped us identify not only different strains in the world, but also those in our own bodies.

But first, a brief timeline of discoveries in genetic sequencing:

The last decade has spelled remarkable changes for research in probiotics, much of which have been attributed to growing access to novel whole-genome sequencing methods, thanks to breakthroughs like The Human Genome Project. With decoded genome sequences of more than 1,000 species of bacteria per person in various conditions, our understanding of the types of bacteria associated with different human health conditions has greatly expanded.

The original efforts behind genome sequencing mainly focused on undesirable bacteria associated with sickness. Some of this attention has now shifted toward food-related bacteria and intestinal commensals, and especially toward the sequencing of probiotic bacteria genomes – a discipline coined in 2009 as probiogenomics.

With full genome sequence data, experts can answer more questions, solve more problems, and make even more advancements in health and medicine. Genomic sequencing of any new strain isolated from a fermented food or the gut allows scientists to answer many questions about it in just a day or two:

• If it is dangerous – if it has the genes to produce histamine or resist antibiotics
• If it is useful – if it has the genes to ferment lactose to lactic acid, for example
• Who its genetic relatives are
• If it is found in the gut of people whose microbiome has been sequenced

PS128: What We Know from Genome Sequencing

When a novel bacterial strain was isolated from fermented mustard greens in 2007, genome sequencing showed that it belonged to the species Lactobacillus plantarum. This new strain, L. plantarum PS128, could be quickly classified as a potential human probiotic because it did not have the known histamine-producing genes or genes for resistance against common antibiotics. How do we know? Because of genomic sequencing. 

Recently Lactobacillus plantarum PS128 was renamed to Lactiplantibacillus plantarum PS128. Why? Again, because of genomic sequencing. 

While the genus Lactobacillus had previously encompassed a large number of lactic acid-producing bacteria species, genomic sequencing revealed that many of these >260 species were rather distantly related to one another, evolutionarily speaking. 

Lactose, which is transformed into lactic acid through fermentation, is common in dairy foods, and thanks to their resistance to acids and bile salts, lactic acid bacteria are particularly beneficial for commercial use. Lactic acid bacteria also play a functional role in fighting pathogens since they create antimicrobial compounds in addition to lactic acid, such as bacteriocin and hydrogen peroxide.

In 2020, a proposal for reclassification was accepted by the official journal of record for bacteria names, which reclassified Lactobacillus into 25 new genera, after genomic sequencing helped reveal clear distinctions in their genetic contents. This new classification included one genus that keeps the old name of “Lactobacillus,” along with the newly minted Lactiplantibacillus, and 23 other novel genera.

The Future of Probiotics

Because of breakthroughs like genetic sequencing and the astonishing speed with which it can be performed with modern technology, our understanding of the microbiome and probiotics has greatly expanded, which has made leaps and bounds in our knowledge of human health. 

Thanks to fecal microbiome sequencing, for instance, experts can determine the profile of individual microbiomes, which could be illuminating for those seeking to understand more about their specific health needs. This type of sequencing is now offered as a service by several companies via at-home fecal microbiome kits, which are available for anyone to purchase online. 

Companies suggest that with these kits, you may be able learn more about your health needs based on their microbiome’s profile, and perhaps determine what probiotics will offer the best benefits. However such “direct-to-consumer” kits are not subject to FDA regulation, and their analytical performance is generally lacking. Many of these kits are fairly expensive, and the jury is still out on the accuracy and validity of at least some of the results, in addition to applicability to human health.

Both previous and ongoing innovations offer a wealth of new possibilities for the research and application of probiotics. For instance, new methods such as metagenomics provide even more information about the analyzed sample. By sequencing the mixture of genomic DNA extracted from a natural source, the community of microorganisms within that sample can be identified. Instead of isolating and culturing individual microorganisms using conventional methods, this far more streamlined approach allows researchers to identify many microorganisms at once, especially microorganisms that have unique growing conditions. Metagenomic techniques have allowed the identification of approximately 70% of the human microbiota, many of which would be difficult to grow in the lab.

The metagenomic approach has the potential to uncover genes, their encoded proteins, and entire gene families – which could be critical in medicine and biotechnology – and new ways to collect data are helping drive the field onward. Such systems will further the research on probiotics and their interactions with the immune system, metabolism, and the microbiome as a whole. 

At Bened Life, we want to be part of a society that uses gut-brain probiotics to solve both everyday and global problems, supporting a high quality of life for people from all walks of life. 

We’re striving for this kind of future through L. plantarum PS128. Learn how it can change your life today!