A recent systematic review in Genome Medicine, authored by Nadja B. Kristensen and colleagues from the University of Copenhagen (Denmark), investigated the impact of probiotic supplementation on the fecal microbiota of healthy adults. The authors, who analyzed seven randomized controlled trials to reach their conclusion, found that probiotics do not change fecal microbiota composition.
The conclusion suggests a commonly assumed mechanism—alteration of gut microbiota composition—may not be how probiotics influence host health. Bacterial diversity in fecal microbiota samples is often used as a shorthand for a ‘healthy’ microbiota, since a diverse collection of species has been linked to measures of better health in many circumstances (although the opposite can also be true). Authors of the recent study found diversity was unchanged when healthy subjects consumed probiotic supplements, a result that was unsurprising to those knowledgeable about the field.
Dr. Mary Ellen Sanders, Executive Science Officer for the International Scientific Association for Probiotics and Prebiotics (ISAPP), wrote a commentary on the article, published in BMC Medicine.
“Do probiotics alter the fecal composition of healthy adults? The answer seems to be no,” Sanders says in an email to GMFH editors. But she says, in the widespread media coverage of this study, many assumed that because one mechanism was ruled out, all mechanisms were ruled out.
“Controlled intervention trials in healthy adults have shown benefits of probiotics,” she says. (See these meta-analyses on probiotics for the prevention of upper respiratory tract infections, urinary tract infections, allergy, and CVD risk.) “This article suggests that the primary mechanism of probiotic benefits may not be altering the composition of the fecal microbiota.”
But Sanders says alternative mechanisms exist: “Probiotics may act through changing the function of the resident microbes, not their composition. They may interact with host immune cells. They may inhibit opportunistic pathogens that are not dominant members of the microbiota. They may promote microbiota stability. They may change the composition of microbiota in the small intestine or the proximal large intestine. So the fact that they don’t change the composition of fecal microbiota does not mean that there is no means for them to impact host health.”
Sanders’ BMC Medicine article raises the question of whether a more fruitful line of study would be to examine how probiotic strains may promote stability of the existing gut microbiota. This kind of study would require comparisons of fecal microbiota at different points in time—before and after exposure to a stressor—in the same individual.
“This recent systematic analysis encourages us to think more broadly about how probiotics might benefit healthy individuals,” says Sanders. “More research is needed to clarify the mechanism or mechanisms of probiotic action.”
Kristensen NB, Bryrup T, Allin KH, Nielsen T, Hansen TH, Pedersen O. Alterations in fecal microbiota composition by probiotic supplementation in healthy adults: a systematic review of randomized controlled trials. Genome Medicine 2016; 8:52. doi: 10.1186/s13073-016-0300-5