Probiotics and the like - do they really work?

The trend for using probiotics is not going away. What are they actually?

Probiotics are live microorganisms, usually bacteria or fungi, that exert a beneficial health effect. In this definition, it is worth noting that until a substance has a proven health benefit, it should not be called a probiotic. If a manufacturer sells a live bacteria as a dietary supplement, and there is no good research to support its health effect - then calling such a supplement a probiotic is a soft marketing lie.

Where can we find probiotics?

The most common are the mentioned dietary supplements, which we can buy in pharmacies. Individual preparations are registered as OTC drugs. It is also believed that naturally occurring microorganisms in food can be treated as probiotics. And such flagship products that may contain potential probiotics are fermented dairy products and pickles (e.g., cucumbers, cabbage).

Do probiotics really work?

I'll start skeptically, because the skeptical approach is closer to me as a scientist. Probiotics are attributed to far more properties than have actually been confirmed. Their marketing and fame are disproportionately positive compared to what the research says.
However, there are specific indications where we have credible evidence that probiotics work. We can speak of a beneficial effect in preventing antibiotic-associated diarrhea, in preventing Clostridioides difficile infection and in shortening the duration of acute diarrhea in children. However, the most significant and spectacular effect is the prevention of some complications of prematurity, such as necrotizing enterocolitis and neonatal sepsis. Many studies have confirmed that some probiotics have beneficial effects here. These are critically important health effects on which a baby's life may depend. Only probiotics of the highest production quality, as well as those with the best proven efficacy in scientific studeis, should be used for premature infants. These preparations are administered to premature infants under close supervision and in the neonatal unit settings.

On the other hand, when it comes to indications such as immune enhancement, the use that is most commercially promoted, the evidence is inconclusive. On the basic science side, we know for sure that probiotics interact in various ways with the gut microbiome, which is very much linked to immunity, and therefore regulate immune function. However, this has not been unequivocally confirmed in clinical trials. And from the overall summaries of the results of individual studies, it appears that probiotics can reduce the risk of upper respiratory tract infections by about 20 percent.

In the pharmacy we can find probiotics (strains or compositions of strains) for various problems and ailments. Even for improving mood - the latter even have their name psychobiotics. Can they really have a positive effect on our psyche?

In fact, certain strains of microorganisms are characterized by the production of substances that affect the microbiome-gut-brain axis. However, when it comes to the clinical significance and relevance in everyday life of such preparations - one can only speculate. Until we have large randomized studies that show unequivocally that a particular probiotic reduces symptoms of anxiety or depression - the marketing use of the term psychobiotic is a bit of a misnomer.

There are toothpastes with probiotics, creams with probiotics....

I've already seen erotic gels with probiotics and floor cleaning chemicals with probiotic. So we even have a probiotic for the floor already.

You are the author of the study on probiotics for which you received the Bohdan and Zygmunt Janczewski Award. What exactly was the subject of this study and how did it proceed?

We tested whether a certain modern multispecies probiotic consisting of eight different strains prevents diarrhea associated with antibiotic therapy in children. The study included 350 children from the age of 3 months to 18 years. These were patients who started antibiotic therapy for various infections. They received either a probiotic or a placebo. We then monitored the children mainly for diarrhea associated with antibiotic therapy. The study was conducted at different centers. I conducted it in collaboration with the researchers from the Netherlands.

And what conclusions were drawn?

It turned out that the probiotic we studied prevented some diarrhea, while not necessarily diarrhea associated with antibiotic therapy. And this is the most interesting “finding” in this study. We often assume that when a patient comes to the hospital and gets an antibiotic, and develops diarrhea - it is antibiotic-related diarrhea. This was also the assumption of the authors of previous studies on this topic. In our study it was different, because we took into account the etiology of the diarrhea. So, we looked at whether the diarrhea is actually due to some non-specific disturbance of the intestinal microbiota - related to antibiotic therapy, for example, or perhaps due to an infection. Let's remember that infections, such as rotavirus and norovirus, the typical viruses that cause gastrointestinal infection, are more common in the hospital than in the home setting.
So, going back to the study, when we analyzed only the diarrhea associated with the antibiotic, we did not detect an effect of the probiotic. It's likely that this effect is absent or very small.
On the other hand, when we summed up the whole group - that is, all patients, including those who had diarrhea of infectious etiology - we found that the probiotic works and that it reduces the risk of such symptoms. So the main question I'm asking myself now is whether the studies so far have proven the effectiveness of the probiotic in preventing antibiotic-related diarrhea, or whether it is effective for infectious diarrhea.

We not only have probiotics, but also other biotics. For example, prebiotics. What are these?

Prebiotics are substrates, substances of various types that are supposed to be selectively used by the human microbiota. Due to the fact that the microbiota “feeds on them” or uses them - they are supposed to modulate it. They can be treated as fertilizer for specific types of bacteria that we already have in the gut anyway. If we selectively stimulate with a substance the growth of a particular species of bacteria to which some health properties are attributed, we will achieve a health effect. Many of these effects coincide with the effect of probiotics.
The best-known prebiotic is inulin present in food. Various types of oligosaccharides are also being intensively studied in this regard, as well as many dietary fiber components. When it comes to food, sources of potential prebiotics are, for example, onions, garlic, bananas, Jerusalem artichokes and whole grain products.

Can prebiotics be purchased at the pharmacy?

Among other things, you can buy inulin in formula form. Of all the potentially prebiotic substances - the most research concerns inulin. Even the European Food Safety Agency (EFSA) takes the position that inulin can be recommended for regulating bowel movements. Last year in “Gut” - one of the top gastroenterology journals, a paper came out about inulin's ability to regulate the reward system responsible for the desire to eat high-energy foods in overweight people. However, for us clinical scientists, it's still not enough to recommend it broadly.

Another biotics are called synbiotics. What are they?

You could say that it is a combination of a probiotic and a prebiotic, that is, a live microorganism plus a substrate for it. However, this is a gross oversimplification, since neither the live bacterium needs to have a demonstrated beneficial health effect, nor the substrate you add to it. This means that, separately, the components of a synbiotic do not have to meet the criterion of probiotic and prebiotic to work together as a synbiotic. It may be that there is an interaction between them that causes a health effect.

I also came across the term postbiotics. What does it mean?

The story with postbiotics is interesting in that their definition is already highly controversial. When the International Scientific Society for Probiotics and Prebiotics (ISAPP) released a document on postbiotics, it sparked a heated debate. Postbiotics were defined as inanimate microorganisms and/or their components that provide health benefits. But what does inanimate mean? Does it have to be killed, or can it just be deactivated? To what extent can microbial elements be divided and individual chemicals extracted from them so that they are still postbiotic...?

Are postbiotics currently available?

Bacterial lysates (mixtures of fragmented cells of various bacterial species) available by prescription and intended to stimulate the immune system can be treated as such. In addition, potentially probiotic bacteria are present in fermented foods. This means that in kefir, in yogurt, in sauerkraut there are not only live bacteria (potential probiotics), but also dead bacteria - potential postbiotics. There are also dietary supplements on the market labeled as postbiotics.

Who are all these biotics for - for everyone, prophylactically, or maybe only for certain groups in certain situations?

Most official recommendations are conditional. This means that even if there is evidence for the effectiveness of these preparations, it is not strong enough to recommend it to everyone. And I am referring here also to the use of probiotics with antibiotic therapy. So, if I have a young patient for whom I am recommending an antibiotic, I tell his parents, “You can give your child a probiotic during treatment. It most likely won't change anything, because most often it doesn't change anything, but it will slightly reduce the risk of diarrhea.”
In a way, therefore, I give parents a free hand. Not giving a probiotic even during antibiotic therapy is not a mistake.
The case is a little different for the elderly. Here I would be more inclined to recommend a probiotic. In popular opinion, it is children who are the most vulnerable group in all diseases. Meanwhile, it turns out that when it comes to severe diarrhea associated with antibiotic therapy, the older we are the higher the risk, and the highest in the elderly. So based on this evidence that I know of, I think that it is the elderly who are on antibiotic therapy who may benefit more from taking a probiotic. And this is a well-proven indication.

And the other indications? Take, for example, the prevention of infections. In this case, our role as researchers and as doctors is primarily to inform the patient that probiotics can be effective - but the research results are inconclusive. Ultimately, then, it is up to the patient to decide whether or not to use a probiotic.
I myself, although I have been researching this topic for eight years, do not use any probiotics, prebiotics, or synbiotics, etc. For me, the evidence of effectiveness is insufficient. On the other hand, the topic itself - insanely interesting to study, because still we do not know very much.

If one already decides to use probiotic preparations, are those registered as dietary supplements or as OTC drugs better?

There is no clear answer. Most probiotic preparations are registered as dietary supplements, single ones - as drugs. What does drug status give us? A stricter registration and inspection process. This means much greater security from state institutions that what the manufacturer declares on the package - is actually in the preparation. That is, that a specific strain is in it and that these are live cells. With dietary supplements, this guarantee is much weaker, which of course does not mean that every dietary supplement does not work. If I would choose probiotics that are registered as dietary supplements, I would look for ones that I know have had clinical trials, have been tested, have been produced for years, and the company producing them has a big reputation.
It is worth mentioning here that there are many publications whose authors checked what was really hidden in a particular dietary supplement that was supposed to be a probiotic. Many times it turned out that either they were completely different strains than declared by the manufacturers, or the bacteria were dead. A striking example is a 2020 publication on premature babies. In one Dutch center, doctors noticed that a probiotic given to premature infants was not working as it should. So they tested several batches of the product, which I stress was given to premature babies, the most vulnerable ones. It was revealed that in some batches there were no declared bacteria at all, but there were contaminations with fecal bacteria. This shows that the production process of these probiotics was virtually unchecked.

Do you think  that the future belongs to probiotics, and as time goes by, there will be more and more clinical studies confirming their effectiveness?

If we are talking about a beneficial overall effect on the microbiome, or restoring the balance of the microbiome, then bacterial consortia, that is, complex preparations that are very abundant in different bacterial species, are much more appealing to me. Several such consortia are currently being studied, and several studies have already been completed. Another idea is gut microbiome transplants, commonly called fecal transplants.
So, if we talk about the future, it seems to me that probiotics will lose importance and give way to more advanced methods of regulation. The microbiome is a whole ecosystem. It is difficult to fix it with a single species - the use of a complex composition of microorganisms convinces me much more strongly.