“The majority of diseases begin in the digestive tract when “good” bacteria are no more able to control “bad” bacteria.” - Elie Metchnikoff, father of probiotics, Nobel Laureate, Physiology or Medicine (1908)
“Like people, not all bacteria get along, and coaxing them to do so is often futile.” - Anonymous
About 40 trillion bacteria belonging to more than 2,000 species along with 100 fungal species, many different kinds of yeast, as well as viruses, archaea, and protists inhabit our gastrointestinal tracts. Assuming one is healthy, all of these germs are either commensals, i.e., benefiting themselves but not giving you any trouble, or mutualists, i.e., benefiting themselves and you.
Probiotics are mutualists; they are germs that, in theory, are good for your health. Look at the shelves of your local grocery store or pharmacy and you will find a variety of probiotics along with prebiotics (non-digestible carbohydrates that nourish our intestinal microbiota) and synbiotics (products that contain both probiotics and prebiotics). Probiotics have spawned a $54 billion a year industry as they have been touted as being beneficial to our health. Nonetheless, not a single probiotic has been proven to work nor has the U.S. Food and Drug Administration (FDA) approved any probiotic. Probiotics are used therefore because of their perceived health benefits. But what do we really know about them? Read on.
History of probiotics. The word probiotic is derived from the Greek words, pro, meaning “promoting,” and biotic, meaning “life.” The World Health Organization and the Food and Agricultural Organization of the United Nations define probiotics as “living microorganisms which, when administered in adequate amounts, confer a health benefit on the host.”
Since antiquity, microbial cultures have been used to ferment food and beverages. This use antedates by thousands of years the mid-19th century discoveries by French chemist Louis Pasteur and the German physician Robert Koch that germs cause infectious diseases. In fact, before turning his attention to the germ theory of disease, Pasteur determined in the 1850s that some germs are responsible for the process of fermentation. Like the fermented beverages beer and wine, in which glucose is transformed by living yeast into alcohol, the same process goes on in cheese, yogurt, kimchi, and in the leavening of bread by yeast. (Pasteur also discovered that heating beer and wine was enough to kill most bacteria that cause spoilage. This heating process became known as Pasteurization that continues to be widely used to kill harmful microbes in milk, bottled juices, and other foods.)
Pasteur recruited Elie Metchnikoff, a Russian zoologist and microbiologist who founded the field of cellular immunology, to his research institute in Paris. There, Metchnikoff laid the groundwork for understanding the theoretical basis for how probiotics work. Metchnikoff suggested that harmful bacteria inhabiting our lower intestine release toxins that are responsible for, among other things, senility. He also championed the idea that a microbial imbalance, that is a deficiency of good germs or an overgrowth of harmful ones, in the lower intestine was the underlying cause of much ill health. In recent years, increasing evidence arising largely from research on the human gut microbiome supports Metchnikoff’s concepts.
Where are probiotics found? Probiotics are found naturally in a variety of foods and beverages, most commonly yogurt, kefir, kimchi, sauerkraut, miso, and kombucha. They can also be purchased as dietary supplements in capsule or pill form. The integration of dietary supplements with inexpensive but good-for-health products, such as yogurt, fruit juices, and cultured dairy drinks, has contributed to their significant market size. The expected global market of probiotics in 2020 was $54. 2 billion, and by 2025 their market size value is forecast to reach $77 billion.
Most commercially available probiotics contain at least eight different species and strains of the most commonly used bacterial genus, Lactobacillus. Other common probiotic bacteria include Bifidobacterium, Streptococcus, and Escherichia. Probiotics are proposed to work in three ways: by outcompeting or knocking out pathogens; by enhancing the integrity of the gut lining; and by suppressing inflammation. But to be effective, probiotic microbes must not only survive the stomach’s acidic environment and bile salts in the upper intestine, they must also anchor themselves in the gut. There is little evidence, however, that they can establish long-term residence in the gastrointestinal tract. Therefore people need to regularly consume most probiotics in order for them to be effective.
Are probiotics safe? Probiotics are generally considered safe. Nonetheless, there are studies that report that many of the high-selling probiotics contain gluten. Therefore gluten-intolerant people, especially those with celiac disease, must be careful about ingesting probiotics.
The dangers of dietary supplements are, however, more disturbing. One such study carried out by the federal government and published in the New England Journal of Medicine in 2015, found that the harmful effects of dietary supplements led to more than 20,000 emergency room visits and 2,000 hospitalizations per year. Equally disturbing is a study published in 2018 revealing the underreporting of harmful effects of probiotics, prebiotics, and synbiotics, not only in the general public but even in randomized controlled trials (RCTs). These studies underscore the importance of carefully reading labels on all dietary supplements before ingesting them.
Are probiotics effective? Even though the FDA hasn’t approved any probiotics to treat or prevent any medical condition, many probiotics are promoted and sold for their ability to: “restore a healthy balance of gut bacteria,” “treat diarrhea,” “decrease the severity of eczema or allergies,” “lower cholesterol,” “boost the immune system,” or “improve mental health.” There may be some anecdotal evidence to support these claims, but there is no scientific evidence that does so.
Nonetheless, a survey found that in 2020 American consumers increased their usage of probiotics from 15% six months prior to the time of the study to 25% in May, an increase of 66%. No one knows why this occurred. This spike in probiotic usage coincides, however, with the time at which the COVID-19 pandemic was hitting the U.S. particularly hard. It suggests to me that these consumers were looking for potential improvement in their immune function or perhaps in their mental health.
Future of probiotics. Given all the enthusiasm for the health benefits of probiotics, why don’t we have any that are FDA approved? After all, the theoretical basis for their effectiveness—including emerging scientific support from the Human Microbiome Project—has been clearly established. I suspect the answer is money. It is extremely expensive to carry out RCTs. As I’ve mentioned in previous Germ Gems posts, FDA approval is dependent on results of sufficiently large RCTs. Recent estimates suggest that the cost of developing a prescription drug that receives FDA market approval, based on its safety and efficacy, is well over $1 billion. Despite these practical challenges, however, a surprisingly large number of RCTs have been carried out, some of which have shown promising results. But until FDA approval is obtained, most physicians won’t prescribe probiotics.
Nonetheless, probiotics are widely used even though there isn’t sufficient evidence to convince the FDA, or for that matter most physicians, that any probiotic is safe and effective to treat or prevent any clinical condition. And their popularity seems to be growing. Based on the remarkable science emerging from research on the gut microbiome, I am optimistic that we’ll soon see results of well-designed RCTs of probiotics, or probiotic-related products, that will support their clinical use.
At the same time that scientific interest has been growing in the gut microbiome, a parallel line of clinical research has blossomed in the field of fecal microbiota transplantation (FMT). As was discussed previously in the November 24, 2019 Germ Gems post, “The Latest Poop on Fecal Microbiota Transplantation,” the use of carefully selected stool samples from healthy donors, administered to patients with recurrent Clostridioides difficile colitis, a bacterial infection that kills an estimated 15,000 Americans per year, has become a first-line treatment of this devastating disease.
In the early days of FMT, donor stool samples were administered to patients most commonly via colonoscopy. In recent years, capsules of fecal matter have been shown to be just as effective. And RCTs have extended beyond C. diff colitis to include inflammatory colitis (ulcerative colitis and Chron’s disease), irritable bowel syndrome, obesity, diabetes, celiac disease, food allergies, multiple sclerosis, Parkinson’s disease, and autism. Although capsules containing human feces aren’t generally considered a probiotic, it seems to me that they are just that, i.e., they contain “good bacteria” that knock off the not so beneficial bacteria, including pathogens. They work just as Elie Metchnikoff predicted. Who knows, someday “poop in a pill” may pop up on the probiotic shelf of your pharmacy or your grocery store. The question is: Will people “buy” it?