Probiotics are beloved by many health-conscious folks. They fit that sweet spot between natural (always good, right?) and medical (must have health benefits). I get legit hate mail if I write anything less-than-glowing about probiotics.
One charming gentleman called me “fake news” and suggested I get my head out of my “pharma fog,” as if Big Pharma and other major corporations weren’t very into selling probiotics for money.
But the truth is, probiotics aren’t automatically always good. Recently, in a few scientific papers and an FDA meeting, doctors and researchers are discussing some of the unknowns and potential harms of probiotics.
Pharmacies are full of things that won’t necessarily heal us — vitamin C, homeopathic drops, probiotics — but we shrug and buy them anyway because, hey, they can’t hurt. But now we have some concrete evidence that probiotics can hurt, if they aren’t exactly the right ones for the health condition you’re trying to treat.
Why Probiotics Are (Sometimes) Good
Probiotics are microscopic living things that we use — typically by eating them, drinking them, or swallowing a pill — for their health benefits. Most are bacteria, but yeasts and other microbes could possibly fit the description.
Our bodies need bacteria and other microbes. The bacteria on our skin prevent other, nastier germs from moving in and causing trouble. We have “good” bacteria in our mouths, noses, vaginas, and pretty much every place where the body meets the outside world. Our digestive tract, and especially our large intestine, harbour huge numbers of microbes, enough to possibly outnumber the human cells that our bodies are made of.
Even at our cleanest, we are covered in germs and we are full of germs. It's OK! That's totally normal. These microorganisms are essential to our health. You probably don't need to mess with them, but if you'd like to try, the terms to know are prebiotics and probiotics.
Research into our relationship with these microbes has exploded in recent years. They produce chemicals that our bodies need, and vice versa. There are hundreds or thousands of species living in our bodies, and they interact with each other like species of plants and animals in a rainforest. We know that a healthy microbial ecosystem is essential to a healthy body.
The only problem: We still don’t know how to define a “healthy” microbiome, and we know even less about how to change it.
“Probiotic” Is Too Vague a Term
Browsing through the Cochrane reviews on probiotics, a theme emerges. Researchers keep wanting to know whether probiotics help for this or that condition, but it’s rare to get a solid, reliable “yes.” More often, the studies are too small to say for sure, or not designed as well as they should be, or half of the studies in the area say yes and half say no.
It’s probably not fair to treat “probiotics” as if it were a single, known entity. Remember our rainforest analogy for the gut microbial ecosystem. Now ask if “animals” could help a rainforest thrive. Maybe? Depending on which animals, and how many, and when and how you released them.
At an FDA workshop, doctors and researchers lamented that even when we know that probiotics can prevent or treat a disease, we don’t know enough to say this strain, in this dose, in these patients, will have this effect.
For example, probiotics can prevent a deadly infection called NEC in premature babies. But neonatologist Josef Neu pointed out that 90 per cent of the probiotics used in neonatal intensive care units in the US have no data supporting their safety or efficacy. Formulations are chosen, instead, based on what’s readily available.
The same is true for probiotics used in other conditions: Patients or doctors get the idea that they should use “a probiotic” and choose from the ones that are available through their suppliers or at a store. But if the brand they pick has different strains or a different dose than what worked in a study, there’s no reason to expect you’ll get the same results.
Bad Things Can Happen
Probiotics appear to be relatively safe, but it’s hard to know for sure. Elaine Petrof, a doctor and researcher also speaking at the meeting, pointed out that studies of probiotics are almost certainly under-counting “adverse events,” the side effects and harmful consequences of probiotic treatment.
After all, probiotics are pills (or drinks, foods, enemas) full of germs, and germs can make people sick. It’s hard to grow vats of bacteria and stuff them in pills, while being 100 per cent sure that you have only grown the bacteria you meant to grow, and absolutely nothing else.
And manufacturers are not always doing enough testing to see what ends up in the pills. Pieter Cohen, a professor of medicine who studies the supplement industry, wrote in JAMA Internal Medicine that dietary supplement companies frequently violate the FDA’s good manufacturing practices, most often because they fail to confirm the “identity, purity, strength, or composition” of the final product.
In 2014, a premature baby died, at eight days old, of a rare fungal infection. Doctors traced the fungus back to a probiotic supplement that the baby had been given since its first day of life. The supplement was supposed to contain three known, safe probiotic strains of bacteria, but was contaminated with the fungus.
We don’t know how often probiotics might be contaminated like this. If you have diarrhoea, and take a probiotic hoping it will help, but the probiotic contains something that makes you sick — you might just assume that your original illness got worse on its own, perhaps in spite of the probiotic.
There’s no standard way to detect or report illnesses that come from probiotics, but it’s worrisome that tests of probiotics have shown they sometimes contain species not listed on the label.
Probiotics can also be antibiotic-resistant. That’s not necessarily a bad thing, especially if you’re taking them to reduce the side effects of antibiotics. But Cohen points out that some probiotics can gift their antibiotic resistance genes to other bacteria they meet — including, potentially, ones that could make you sick. Canada has banned probiotics that have these types of antibiotic resistance genes, but so far the US has not.
We’re Still Learning How Probiotics Interact With Our Native Gut Microbes
Companies hucking probiotics make a big deal about how our gut microbes are so important to our health (true) and this means we need to add good bacteria to our gut by taking probiotics—but that’s not quite how they work.
Typically, probiotic bacteria don’t take up residence in our gut. That doesn’t mean they don’t work; it’s totally possible they shake things up and then move on when their work is done — the Clint Eastwood characters in a microbial wild west.
But the relationship is probably more complex than that. First, researchers typically use stool samples to figure out what’s living in our guts, but the bacteria in poop aren’t necessarily the same ones that are living on the inner surface of our intestines. It’s easy to collect stool samples, much more inconvenient to have your study volunteer (or experimental animal) submit to a colonoscopy to sample what’s going on deep inside. Much of the research that’s been done on the gut microbiome relies on these not-necessarily-reliable stool samples.
Now, two recent papers in the journal Cell throw a wrench into the works. Both found that probiotics interact with our native microbes in complex and possibly harmful ways.
In one study, people took antibiotics, and then the researchers tracked how long it took their gut microbes to return to normal. Many of us take probiotics alongside antibiotics to mitigate the effects, like reducing the diarrhoea that results from antibiotics killing off our natural flora. But in this study, the researchers were able to show that probiotics made it harder for subjects’ guts to return to normal.
The other study, done by the same team of researchers, found that some people are “resistant” to being colonised by probiotics, while others easily allow the probiotic strains to take up residence. This suggests that the effects of probiotics may vary by person, not just by the condition you want to treat.
It’s not too far a leap from those results to suggest that probiotics should be personalised. But the researchers behind the studies also run a personalised nutrition service, so I’m a little bit sceptical.
Probiotics Fall in a Weird Space The Government Doesn’t Know How to Regulate
If you walk into a store and buy some probiotics that are packaged as pills, they will bear a “supplement facts” label; the government considers them a supplement, like vitamins. A supplement can’t say that it treats, prevents, or cures any disease, but it can make vague claims like “boosts digestive health.”
If you buy the same bacteria as part of a food, like yogurt or a Yakult drink, it’s considered just a food. Bacteria are a normal component of yogurt, after all.
But a dose of beneficial microbes can also be a drug. If you have a digestive disease, like the notorious Clostridium difficile infection, you may want your doctor to give you a treatment that contains bacteria from somebody with a healthy microbiome.
This treatment is made from a healthy donor’s stool, and is best known as a faecal microbiota transplant, or FMT (even if it’s delivered by dried material in pills). In this case, the FDA considers the bacteria to be a drug. (They reportedly considered classifying it as a tissue transplant, but the bacterial cells aren’t part of the donor in the same way a blood or tissue donation is.)
The difference is that something is a drug if it’s meant to treat, prevent, or cure a disease. If you want to take probiotics while you’re on antibiotics, you can grab a supplement at the grocery store to do that (with the caveats mentioned above, of course). But if a pharma company wants to market a specific strain and dose of probiotics to prevent antibiotic-associated diarrhoea, they would have to get that probiotic approved as a drug, with all of the paperwork and clinical trials that a drug application involves.
That’s why, in part, the FDA held their meeting; they’re trying to figure out what probiotic drugs would look like, and what kinds of tests and labelling they should require. But all of that is unknown for now.
The Bottom Line: Unknowns Will Stay Unknown For a While Yet
The only thing that’s likely to improve in the near future is a tweak in labelling: the FDA is asking manufacturers to add CFU counts to labels.
CFUs, or colony-forming units, roughly measure how many live microorganisms are in the product. Many speakers at the FDA meeting emphasised that labels should also have to identify the specific strain of bacteria they use, not just the name of the species.
(Just like dog breeds, bacteria can come in different varieties while still being the same species.)
But all the other unknowns remain. Does a probiotic product contain exactly what’s on the label, and no more? Will it help? Will the microbes in the product starve to death in my gut, if I don’t eat certain specific foods?
Is it harmless? Has it even been tested on people like me? Many trials exclude people who are immunocompromised or have digestive diseases, even though these are the people who stand to benefit the most from probiotics or FMT.
But you wouldn’t know any of that from probiotic companies’ marketing. Meanwhile, probiotics are a favourite of nutritionists, chiropractors, and other experts—legit ones and quacks alike. There really is a lot of evidence of benefit, and we know so little about the risks that it’s easy to forget there even are any.
There’s also the huge problem that if one probiotic works for one condition, that doesn’t mean all probiotics work for any condition. There are hundreds of probiotics, and surely they all aren’t good for everything.
We have a hard enough time, as a society, understanding vitamins for chrissakes. These are a defined number of substances, we know you die without them, we have their specific molecular makeup, and we can manufacture them at will. We know what doses will prevent and treat diseases. And yet, people still can’t keep straight when and whether you need them.
For example, one symptom of magnesium deficiency is insomnia, so there are folks out there selling “anti-stress drinks” with magnesium to help you sleep. That’s not good logic — most people aren’t magnesium deficient — but it sells.
Probiotics have the same cachet as vitamins, with a more nebulous scientific backing. Surely some are safe, and some are effective, but which are they? It will be a while before science has any definitive answers.