How many sugars did you put in your coffee this morning? One or two? Maybe 18? It turns out, that what might be the most concerning is not the amount of sweetener but the type. If pink packets of Sweet’N Low trail in your wake, you might want to check in with your microbiome.

In a study published Friday in the journal Cell, researchers in Israel found there’s nothing low about Sweet’N Low and many other artificial sweeteners marketed as non-nutritive — having zero to no calories or physiological effects on the body. Instead, these compounds appear to alter the microbiome in healthy individuals, prompting unsettling changes in glucose, insulin, and other hormones involved in the glycemic response (aka the body’s response after eating or ingesting carbohydrates).

“This current study… is the first [of its kind] to causally or mechanistically look into possible side effects of all four common artificial sweeteners on the human microbiome and to assess whether in some people, [artificial sweeteners] will also impact glycemic responses through the microbiome,” Eran Elinav, the study’s lead researcher and a professor at the Weizmann Institute of Science in Israel and the German National Cancer Center, tells Inverse.

So far, it’s looking like artificial sweeteners are failing at the one task they had: Rather than a healthy alternative to sugar, these substances may pose a considerable threat to human health.

Here’s the background — Artificial sweeteners first entered the food industry with the accidental creation of saccharin (also known as Sweet’N Low) back in 1879, followed by aspartame in 1965, and sucralose (aka Splenda) in 1976. While the first century was fraught with questions of health and safety, and regulatory bans, artificial sweeteners slowly gained acceptance and popularity, booming in the 2000s when consumption skyrocketed to astronomical heights.

Sweetness without raising blood sugar or calories has been the major selling point of these sugar substitutes. But over the last forty years, there’s been much discussion within the medical and scientific community over whether these compounds are actually healthy. Studies in animals and humans have largely been mixed or inconclusive. However, with the rise of microbiome research, the trillions of microorganisms residing in our bodies emerged as the bridge between artificial sweeteners and the body’s metabolism.

“We’ve been researching the interactions between diet and the microbiome for many, many years — actually from the formation of the microbiome field in which I am very lucky to be a part of,” says Elinav.

Through research into what he describes as “personalized nutrition” — that identical foods trigger unique glycemic responses in different individuals — Elinav arrived at the idea that artificial sweeteners may not be influencing human cells directly. But they are doing something to the microbiome.

(If you’re wondering whether regular sugar does anything to your friendly intestinal microbes, Elinav says that’s less of a concern. Our bodies absorb the sweet, white crystals super quickly; hardly any teeny tiny granules survive past the duodenum, or small intestine, which is where food enters after it passes the stomach.)

What they did — Expanding a 2014 study where Elinav’s lab found that eating artificial sweeteners was linked to an off-kilter gut microbiome and high glucose levels in mice, the researchers wanted to see whether this phenomenon occurred in humans.

Whittling down 1,400 individuals to 120 based on whether they had ever consumed artificial sweeteners (I mean, who hasn’t?), the healthy volunteers were followed for one week to get baseline measurements of how their gut microbiomes were (through poop samples), glucose levels, and overall health. They were then randomly divided into six groups: two controls and four test groups were given sachets of aspartame, saccharin, stevia (a plant-derived sugar substitute), or sucralose to ingest daily for two weeks. Glucose tests were done before and after the participants took their sachets to track trends.

To make sure that any changes they saw during the two-week period were, in fact, because of an altered gut microbiome, the researchers collected gut bacteria from 42 individuals: Four from each test group that had the most potent responses and three from each group that had the lowest responses to eating artificial sweeteners. These bacteria were implanted in germ-free mice (animals that, for the most part, lack a microbiome) to see if what happened in the donors would duplicate in the tiny critters.

What they found — Although the healthy test subjects were taking amounts well below the FDA recommended allowance levels for artificial sweeteners, Elinav says they still saw glycemic responses to all four types of sweeteners (yes, even stevia), though it was more pronounced for volunteers on saccharin and sucralose, and the mice that received their gut bacteria.

“Recipient mice developed glycemic alterations that reflect those of the human consumers, and that happened in all four sweeteners,” explains Elinav. “In other words, the top responders of all four sweeteners had a changed microbiome that had a capacity to induce sugar disturbances.”

These blood sugar disturbances, characterized as massive spikes in one’s glucose levels, weren’t seen among humans who didn’t respond as strongly to artificial sweeteners, as well as mice with their corresponding donated microbiome. Neither was it observed among controls, but that’s to be expected.

“[These findings mean] that these microbiome capacities to change the glycemic response were personalized and happened in some, but not all, individuals,” says Elinav. In other words, whatever the unique composition of your microbiome, so too determines your unique metabolic response to an artificial sweetener.

What it means for the future — This research is just the first start to unraveling how sweeteners and so many other food additives sway human health through an intermediary like the microbiome.

The identity of the chemicals the microbiome is secreting after it’s powdered with synthetic sugar still needs discovery, although Elinav has some hunches.

“We’ve measured the small molecules secreted in the blood of people — partially by the microbes — and found big differences that are induced by sweeteners,” he says, explaining that some may be chemicals that suppress the growth of competing microbes or may impact the immune system and cause inflammation.

The microbiome researcher is quick to point out that he’s simply a scientist, not a doctor or public health professional. He can’t make any recommendations on whether you should go cold turkey on the Splenda or Sweet’N Low. But he does say that it’s very possible that for certain people, depending on their microbiome, consuming artificial sweeteners could push the dial toward diabetes, obesity, or other metabolically-linked diseases.

“We need to prove something is safe until proven otherwise. It’s not our role to presume something is safe until it is proven to be unsafe,” he says. “[That] conclusion should be drawn by those responsible for making recommendations.”

Considering the World Health Organization released an extensive analysis of the health effects of artificial sweeteners back in April, hopefully, the powers that be are for sure taking some notes.