Are Probiotic Preparations Effective?

Practically every scientific and not-so-scientific review on probiotics begins with a mention of Ilya Mechnikov (and we will do the same), who first spoke about yogurts and lactobacilli as a possible explanation for the longevity of the Bulgarian region. And in the 73rd year, prompted by Canadian urologist Andrew Bruce, scientists and clinicians broadly started talking about probiotics for vaginal indications. A definition of probiotics gathered together was given by Roy Fuller in 1989, calling them “living microorganisms which, when administered in adequate amounts, exert a beneficial effect on the macroorganism by improving the balance of the intestinal microbiota.” That is roughly how this magical word "probiotic" should be understood.

The modern world of probiotics has advanced far beyond the “lactobacillus–bifidobacteria” dichotomy in both species diversity and applications. In addition to traditional yogurts, pickled cabbage, and capsules with lactobacilli after a course of antibiotics, there exist vaginal probiotics, skin-care products, or, for example, ice cream or even household cleaning agents. It is fair to note that the "probiotic" nature of some such products is little more than marketing fantasy that sometimes crawls out from the skin to stay in fashion. But, not without some truth — alongside mere trendy features there are also products that truly have efficacy.

In this short review — what concerns probiotic preparations that travel to our intestines.

Speaking about modern probiotic preparations, it should be said that the majority of them include lactic acid bacteria and bifidobacteria. However, there are also preparations based on spore-forming microorganisms (Bacillus genus), yeasts, and even intestinal rods. Spore probiotics and some yeasts show pronounced antagonism toward many intestinal infections and therefore are often a superb alternative to antibiotic therapy.

How do "they" do it?

Probiotic effects can be realized by many pathways. And, honestly, not all mechanisms are yet understood and continue to be the subject of intense debate among researchers. Most often, the discussion centers on the antagonistic action of probiotic strains — they produce lactic acid and antimicrobial substances (varied: from diverse peptides to antibiotic-like substances such as nisin, or simply hydrogen peroxide). In other words, everything happens, like in a traditional American movie: the world (the gut) suffers from villains (some staphylococcus or another pathogenic or opportunistic microbe), but good guys (probiotics) come in and defeat the bad guys (and antimicrobial peptides act like grenades). Or there is an apocalypse (antibiotic intake), followed by post-war times (antibiotic-associated diarrhea), where "the good smart guys" (probiotics) again build skyscrapers (restore our "gut prosperity").

Additionally, some probiotic microbes can synthesize a bunch of molecular “keys” that can tune the body’s functioning to the desired state, for example, reducing allergic reactions or inflammation. Or they include their own enzymes and, for example, break down cholesterol that does not return to our bloodstream from the gut.

Today there is a discourse about whether such effects are always caused by a substantial change in our microbiome. Because many studies indeed report the absence of changes in the species composition of the microbiome upon probiotic consumption. There are also studies that suggest that the changes occur in the thin intestine rather than in the studied exit aliquot we typically analyze.

There is also a view that therapeutic effect may be achieved precisely due to the temporary action of the metabolites of the bacteria used, and that this is sufficient to establish microbial homeostasis.

And, of course, probiotics tend to fill vacant ecological niches in our gut after antibiotic action, which by itself prevents the development of other pathogenic microorganisms.

Are they effective or not?

A poor headline of one of the articles, published by the BBC, where probiotics were called 'quite useless' (based on only one study, in which it was found that far from all and far from always probiotic strains take up residence in patients’ guts), added fuel to the fire of the controversy over evidence-based medicine and the trend of skepticism.

First, as we just mentioned, the efficacy of probiotic preparations may not always directly depend on their “residency” in our guts.

Second, our intestinal microbiomes are very diverse and indeed do not always readily welcome new guests with “bread and salt,” and are willing to share living space and food.

And third, to say that all probiotics are ineffective, or that all are effective — is like saying that all people are good, or all people are bad. Because these are living organisms. Like us.

Not all strains used in probiotic preparations are equally potent or even studied. Large-scale, detailed studies require substantial budgets. A typical minimal scope of such research includes the identification, safety studies in animals (hello to animal-rights advocates) and humans, the ability to survive the gastrointestinal tract, the ability to adhere to epithelial cells and show some antagonistic activity against at least some pathogenic microbes, as well as the optimization of biomass production and survival of microbial cells during drying for the storage period. All this already drives a substantial budget. Add to this clinical studies of efficacy in diarrhea of various etiologies in different age groups, allergies, high cholesterol, and other desired cases, as well as analysis for absence of mobile antibiotic-resistance genes, and you get the budget of some small island nation. Accordingly, not every package of a probiotic preparation truly contains comprehensively studied strains with proven efficacy.

Therefore, a probiotic differs greatly from another probiotic — both in composition and in efficacy.

What do scientific studies say?

Traditionally, probiotics are successfully used for gastrointestinal disorders of various etiologies, including infectious diseases and the use of antibiotics. A analysis of thirty-three studies (~6,000 patients) showed a moderate protective effect of probiotics in antibiotic-associated diarrhea and also a reduction in its duration when used at doses greater than 5 × 10^9. The results for widely known strain LGG (Lactobacillus rhamnosus GG) are particularly successful. Interestingly, for diarrhea caused by Clostridium difficile, the most effective preparations contained lactobacilli Lactobacillus casei. Yeasts Saccharomyces boulardii, and lactobacilli of the species Lactobacillus reuteri are also recognized as effective against antibiotic-associated diarrhea.

Controversial data on the effectiveness of probiotics for inflammatory bowel diseases (IBD). Although some probiotics led to remission in ulcerative colitis, the authors of the review do not expect substantial improvement with probiotics in Crohn’s disease.

Shown the effectiveness of the strain Lactobacillus rhamnosus GG (LGG) in preventing atopic dermatitis when taken by pregnant women and in the first six months by infants. This protective effect had a fairly prolonged action. However, it is fair to say that such a clear positive picture was observed only in studies of the LGG strain; a meta-analysis of a broader range of probiotic strains did not show a single unambiguous therapeutic effect.

An analysis of 22 studies (over 3,000 patients) showed the ineffectiveness of probiotics for constipation in children.

An analysis of 25 studies involving more than 4,000 patients demonstrates a truly high level of effectiveness of probiotics when used in preterm infants (less than 37 weeks gestation and less than 2500 g). This reflected in shorter time to reach full enteral feeding and more effective weight gain. It also showed a marked protective effect of probiotics in preventing the development of necrotizing enterocolitis and sepsis.

Thirteen studies involving more than 2,000 patients show an increase in the effectiveness of Helicobacter pylori therapy when combined with probiotics. Some studies even point to some species-specificity of the obtained efficacy.

A number of good results were obtained applying probiotic preparations in the field of gynecology. Vaginal probiotics demonstrate effectiveness in fighting bacterial and fungal vulvovaginosis and reducing the frequency of infectious relapses.

Despite the latest studies on the involvement of the gut microbiome in the etiology of various neuropsychiatric disorders, no therapeutic effect has been found yet of existing probiotic preparations on autism symptoms in children.

Also no successful results have yet been obtained in applying probiotics to treat patients with schizophrenia.

What to expect in the next decade?

Currently (2019) there are no probiotic preparations on the market with proven efficacy for treating psychiatric and neurological disorders such as depressive states, schizophrenia, or autism. However, there are all prerequisites for their appearance.

There are also data on certain strains and their compositions that effectively promote lowering cholesterol. Therefore, new competitors will soon appear for statins.

Animal studies show cardioprotective effects of Lactobacillus rhamnosus GR-1. This will also soon lead to new products in cardiology.

Another promising direction could be the creation of probiotics with detoxifying properties. There are studies showing the ability of some strains to prevent the absorption of heavy metals, aflatoxin, and other toxins.

It is also expected that the species spectrum of strains used will expand far beyond Lactobacillus–Bifidobacterium. New and new kinds of microorganisms are entering the probiotic arena. Among them, for example, Akkermansia muciniphila, which creates such wonders for metabolism and immunity that sellers of weight-loss pills are already rubbing their hands and eyeing resorts in the Maldives.

Should you take probiotic preparations and how to choose a truly effective probiotic?

We will refrain from giving concrete recommendations — this is the duty of your family doctor. We can only note that simply “for prevention” consuming probiotic preparations is not advisable. If “there” everything works — let it work, don’t interfere. But if there are indications and you really need to choose one of the preparations, pay attention to the following:

Dosing. Scientific studies indicate that a pronounced therapeutic effect of a probiotic preparation is possible at a dose of not less than 10⁹^ microbial cells per dose.

Full strain names. Those manufacturers who truly have something to brag about always specify not just "lactobacilli–bifidobacteria" or even the Latin names, but indicate the names and numbers of strains. For an advanced consumer this is an opportunity to “lookup” this number in PubMed and read about the talents and achievements of this particular strain. Thus one can verify the listed indications against the same evidence base.

Manufacturer. It is important that the manufacturer listed on the package is still a pharmaceutical company with a good reputation, not a makeshift dietary supplement generator that perhaps has never even heard of GMP standards. This is not only a question of efficacy but also of safety, because in the production of microbial preparations, high-quality raw materials and meticulous microbial control at all stages are crucial.

Stay healthy!

Photo by JOSHUA COLEMAN on Unsplash