There’s a pungent cloud of hype and hope around probiotics—and researchers have long tried to clear the air about what the bowel-blasting products can ( and mostly can’t) do. Now, a new set of studies offers a gut-check on funky claims, ripping current probiotics as likely ineffective at boosting health and potentially even causing harm.

In the two studies, both published this week in the journal Cell, Israeli researchers report that bacteria taken in supplements, aka probiotics, often have little impact on healthy people’s innards and, at worst, can elbow out native populations of microbes.

In the first study, the researchers found that healthy microbial populations in people’s plumbing tends to flush out the newcomers. Thus, the microbial interlopers from supplements have little impact on resident microbiomes—and, by extension, consumers’ health—and are largely just pooped out.

But probiotic strains can more easily take root in the gut if a person takes a strong dose of antibiotics that beats back their beneficial bacteria, the researchers found in the second study. This finding might suggest that the living supplements could help rejuvenate the intestinal inhabitants after an antibiotic onslaught—as probiotic makers would surely like to claim. But in fact, probiotics made it harder for the healthy, native community of gut bugs to recover, the researchers found. People who took probiotic supplements to rally their microbiome after antibiotics didn’t regain their healthy communities for as long as five months afterward. People who didn’t take anything after their antibiotics did.

The stinky findings are not shocking given past disappointing and inconclusive data on probiotics. A 2016 review of randomized controlled studies concluded that probiotics had almost no effect on the overall mix of microbes in people’s poop. While other studies have pushed out evidence of microbial changes from probiotics, there’s still little data on what those changes might mean in terms of health and what our microbiomes are actually doing for us. And previous studies looking specifically at probiotic use after antibiotics also found the supplements were ineffective. For instance, probiotics couldn’t stop up antibiotic-induced diarrhea or thwart the more serious antibiotic-associated gut invader, Clostridium difficile.

So far, such findings haven’t deterred consumers from plopping down money for probiotics in the hopes of better bowel health. Probiotics are an ever-growing market, with 3.9 million adults in the US using either probiotics or prebiotics. They’re among the most commonly used dietary supplements.

And the idea behind probiotics still isn’t a foolish one. The communities of microbes thriving in our intestines do all sorts of useful things: they can alter our immune response, influence our hormones, protect us from infectious germs, help us digest and process foods, and keep things, well, regular. Optimizing and stabilizing such communities could have a lot of perks and help thwart disease. The trouble is, we don’t know enough about our complex, highly variable microbiomes to manipulate them effectively yet—despite what probiotic makers will try to tell you.

Some good news is that the new set of studies has some helpful hints for moving forward.

Flushed out

For the first study, researchers at the Weizmann Institute of Science in Israel turned to a commercially available probiotics product that included 11 strains of bacteria. Those bugs are commonly used in products and believed by marketers and some consumers to improve health. The inventory includes: Lactobacillus acidophilus, L. casei, L. casei sbsp. paracasei, L. plantarum, L. rhamnosus, Bifidobacterium longum, B. bifidum, B. breve, B. longum sbsp. infantis, Lactococcus lactis, and Streptococcus thermophilus. The researchers independently confirmed that those bacteria were alive and kicking in the probiotic mix.

Fifteen healthy adults agreed to have their guts and stool probed for preexisting microbes before entering the trial. They did colonoscopies (for sampling the microbes in the lower gastrointestinal tract) and endoscopies (for sampling the microbes in the upper GI tract). Then 10 volunteers took a course of probiotics twice a day for four weeks, and the remaining five got a placebo. They all had their feces sampled throughout and had colonoscopies and endoscopies again three weeks after the treatments.

The researchers found a lot of microbial variability among individuals before and after the treatments. But for the most part, the probiotics seemed to have little effect. Those that took probiotics clearly pooped them out while they were taking them. The five that got the placebo didn’t—as was expected.

Six of the 10 people in the probiotic group were dubbed “permissive” because some of the probiotic strains seemed to stick with them in their lower GI tracts at low levels after the four-week treatment. The remaining four were dubbed “resistant” because the probiotic strains seemed to flush out completely. Importantly, these designations were based solely on the direct intestinal probing—not what the researchers could see in the stool samples. Those deposits were nearly useless for figuring out which probiotics were colonizing the gut.

When the researchers looked even more closely at the intestinal data, they noted that the permissive people tended to have lower levels of probiotic strains in their guts before the treatment than the resistant crowd. Thus, the probiotic strains may have had an easier time finding a niche in the permissive group due to less competition from the resident microbes.

Overall, for the researchers there were two main takeaways from the study. The first is that poop samples aren’t that useful for gleaning information about whether probiotic bacteria are blooming in the bowels. This is rather notable, because many microbiome studies rely on fecal samples as a proxy for microbiome residents. The second takeaway is that the microbes already present in our innards seem to dictate which probiotic strains have a chance of colonizing. Thus, successful probiotics may have to be custom designed for individual microbiomes.

Microbial mayhem

Of course, this study was all in healthy people. Many consumers turn to probiotics when they’re not healthy. In the second study, the researchers aimed to look at the effects of probiotics on microbiomes that were known to be out of whack.

For this, they had 21 healthy adults take a seven-day course of antibiotics that knocked back their microbiomes. This kills off resident microbes indiscriminately and causes “dysbiosis,” which is essentially the collapse of microbial community structure.

Eight of the 21 participants then took the 11-strain probiotic mix twice a day for four weeks, while seven took nothing—the control group. The remaining six participants got fecal transplants of their own poop collected prior to the antibiotic treatment (this is a so-called autologous Fecal Microbiome Transplant, or aFMT.) The researchers again used stool samples and intestinal probing before and after treatments to keep a watchful eye on gut dwellers.

In this study, the probiotic strains flourished. In the dysbiotic guts, probiotic strains bloomed in the lower gastrointestinal tracks, forming stable, active colonies. This might seem like a good thing. But compared with the control and aFMT groups, the probiotic subjects fared the worst in terms of reestablishing their microbial communities. The participants that got an aFMT saw their healthy, native inhabitants rally within as little as a day of their transplants. Those that got nothing after their antibiotics had their communities recover within 21 days.

But the probiotic group—who were now colonized with the probiotic strains—stayed in a state of dysbiosis for as long as five months after their antibiotic treatment. The load of bacteria in their feces was lower, and the microbial communities in their lower GI tracts were still significantly disturbed. With further digging, the researchers found that the probiotic usurpers seemed to spur immune responses in the gut that could inhibit native microbes. In lab studies, the researchers also noted that the probiotic strains seem to secrete unidentified factors that could inhibit the growth of microbiome residents.

The two studies have limitations, of course. They were both small. And other probiotic strains than the 11 tested could prove more useful—or at least less concerning. Probiotics may be beneficial for different patient populations, as well. In both studies, the researchers used healthy adults, while infants, children, or the elderly may have different experiences with probiotics. And people with specific conditions could benefit in specific ways.

Still, in all, the researchers concluded that use of probiotics “may not be risk-free.” And in the case of boosting the microbiome, they conclude:

Like any other medical treatment, [probiotics’] potentially beneficial pathogen-repellant activity (which remains to be proven or refuted) may carry a tradeoff risk of adversely impacting the rate and extent of indigenous microbiome recolonization.

Cell, 2018. DOI:10.1016/j.cell.2018.08.041

Cell, 2018. DOI: 10.1016/j.cell.2018.08.047 (About DOIs).