Probiotics: A DANGER to your microbiome?

 

Headlines lately have been reading: “Probiotics are dangerous” and “Probiotics might not do anything for your gut microbiome—and could even be bad for it.”

The headlines were prompted by two recent studies performed by an Israeli group that media interpret as suggesting that probiotics don’t work and may be even be harmful. Is their interpretation accurate? Let’s take a look.

The first study, Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT (fecal microbiome transplant), examined what happened with antibiotic administration followed by a probiotic supplement, fecal transplantation, or nothing, with return to prior bowel flora composition fastest with fecal transplant, delayed by probiotic use. The administration of probiotic in mice and 8 humans was associated with a 5-month or more delayed return to previous bowel flora composition.

The second study from the same group, Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features, in which bowel flora composition was studied before and after administration of the same probiotic preparation used in the first study, did not show that probiotics were ineffective in altering bowel flora composition, as the media reported. It showed that alterations in bowel flora composition after probiotics were highly variable from individual to individual, some showing no change, others showing dramatic change. It suggests that unidentified individual factors (baseline bacterial populations, mucous composition, prebiotic fiber intake, sugar and other components of diet, etc.?) influence the impact of probiotics.

While these studies are detailed and elegant, the biggest error in logic in the first study is that we should never assume that a return to pre-antibiotic bowel flora status means a return to normalcy. This was the defining metric in the first study: whether or not there was a return to pre-antibiotic or pre-probiotic bowel flora composition. The problem is that the great majority, probably all, modern humans start with at least some degree of dysbiosis, if not small intestinal bacterial overgrowth, SIBO, that is wildly common. A return to the status quo means a return to some degree of dysbiosis. Passing judgement on whether some collection of species is better or worse based on return to baseline is foolhardy. Interestingly, probiotics after antibiotics favored a return enriched in Akkermansia that is a desirable development, given this organism’s ability to enhance the health of the mucous lining and support other beneficial species. And the reduced return of Clostridia species after probiotics is also not necessarily a bad thing, as many Clostridia are pathogens. In other words, the first study discounts the entire value of probiotics, suggesting that their only potential value is to accelerate a return to a prior dysbiotic state, a deeply flawed assumption.

The only firm conclusion from the second study is that the effects of this one probiotic preparation are highly variable. We cannot generalize this to all humans, all probiotics, and cannot say what factors influence this variability. Also, note that no efforts were made in either study to cultivate healthy bacterial species with prebiotic fiber supplementation, consumption of fermented foods, etc. only administration of a single probiotic. And the effects of one probiotic preparation should not be generalized to apply to all other probiotic preparations, accepting that nobody yet knows what constitutes an ideal probiotic.

The biggest problems in drawing any conclusions from these studies:

1. A return to “normalcy” is not necessarily a return to a healthy microbiome—it is just a return to the likely dysbiotic status quo.
2. There is good evidence from several clinical studies that, when probiotics are taken concurrently with antibiotics, there is reduced likelihood of Clostridium difficile infection, a potentially life-threatening proliferation of an organism that emerges in the wake of antibiotics. This alone is a very good reason to take a probiotic during and after antibiotics. No, it does not permit full recolonization with the previous microbiome, but it helps prevent C. difficile from gaining a foothold. This alone is a good reason to take a probiotic.

Nonetheless, these studies add a small amount to our overall understanding of the microbiome. Among the lessons learned or, at least, re-emphasized, are:

1. We still have tons to learn about this hugely important thing called the microbiome.
2. We really need to identify the microbial species and strains that are essential for overall health. Current probiotic preparations are crude with few products specifying strains, only genus and species. But strain specificity is crucial. To illustrate: You and I have E. coli in our intestines; as long as they are kept from over proliferating by healthy competing species, E. coli is harmless. But get exposed to the E. coli O157:H7 from contaminated lettuce and you can become very ill, even die—same species, different strains. So strain makes a world of difference. Yet most probiotics do not specify the strain contained in commercial probiotic preparations. As we better understand the benefits or lack of benefits of various strains, commercial probiotics will need to specify their strains.
3. Probiotics are crutches to restore or maintain healthy bowel flora–And we already knew that most probiotic species do not colonize the colon forever, as they are essentially gone within weeks of ingestion. What does that mean? Are we supplementing with the wrong species or strains? Are the probiotics ingested insufficient to overcome resident organisms? Is the modern gastrointestinal tract inhospitable to probiotics because we have disrupted the mucous lining, the intestinal lining, ingest dietary factors that are disruptive, or other factors?
4. Those of us engaged in more comprehensive efforts to restore healthy bowel flora, as we do in the Wheat Belly and Undoctored programs, and consume lactate-fermented foods, include generous quantities of prebiotic fibers in our diet, and work to remove factors that disrupt the microbiome such as herbicide/pesticide-laden foods and stomach acid-blocking drugs, also recognize that a probiotic is just one component of a broader effort.
5. We already knew that stool sample analysis does not fully reflect the composition of bowel flora, as there are microbes sequestered in the mucous lining. Also, most methods used to analyze bowel flora do not identify all species.
6. The temporary colonization of the upper gastrointestinal tract seen in these studies suggest that at least some of the value of probiotic species may be in people with small intestinal bacterial overgrowth and not necessarily in altering colon flora composition—a regional difference but not a species difference.

Bottom line: Rather than dismissing the value of probiotics outright, we just need to accept that there are SO many more lessons to be learned about the human microbiome. These studies add to our overall knowledge but raise more questions than answers. The biggest mistake in logic made by these studies—and the simpleminded media—is to assume that a return to pre-antibiotic bowel flora status is not necessarily a good thing—it may even be a bad thing. Also, dismissing the value of probiotics based on a single collection of 11 species is like saying that, because penicillin didn’t work against an E. coli bladder infection, all antibiotics are therefore ineffective—a gross and unjustifiable generalization.

Getting to a place in which we have truly effective strategies to restore a healthy microbiome will not be a straight line, but a zigzagging path with many helpful lessons and mistakes along the way. But we at least have to take the journey, as management of the microbiome is likely to be among the most powerful strategies ever in the history of human health. In the meantime, we need to logically process new developments and not give into the attention-grabbing headlines of media that barely understand what they are reporting.