Artificial Sweeteners: The Sour Alternative

Artificial sweeteners were a great idea in the fight against sugar consumption. Excessive amounts of sugar come with consequences such as obesity, inflammation, cardiovascular problems and more. Finding an alternative was a must.  Enter artificial sweeteners, also called non-nutritive sweeteners or sugar substitutes. These low and zero-calorie substitutes allowed us to keep eating sweets without having to worry about the consequences. They replaced sugar in many snacks and drinks and kept us all happy.

Originally seen as a godsend by many health-minded individuals, including doctors who recommended it for weight-loss in patients with type 2 diabetes (Suez, 2014), this seemingly healthy alternative may not be as great as the hype accompanying it.

Sweeteners such as saccharin (Sweet’N  Low), sucralose (Splenda), aspartame, stevia, acesulfame-potassium (Ace-K), and neotame (Nutra Sweet) were quickly accepted by the FDA, despite controversial results in early studies. (Suez 2014, Swithers 2013) The research was not thorough and the public was excited for a promising alternative, rushing the decisions. Many years later, we cannot close our eyes on the effects, the consequences are as ugly as what we were trying to avoid and more.

In a world where obesity, type 2 diabetes and metabolic diseases are becoming more prominent, there is a need to dig deeper and understand how our bodies react to artificial foods. One of the big-ticket answers is the microbiome. Diet and the gut microbiome have increasingly been looked at as the cause of diseases. The microbiome describes all the microbes and their potential to promote good or bad health; they play a role in food digestion, fermentation, pathogen prevention and developing our immune systems.(Bian 2017a and b, Suez 2015)  The microbiome is modeled by our eating habits and anything we ingest. It is vital to keep it balanced and healthy.

Central question

Many scientists have been considering the interaction between diet, microbiome and metabolic problems. The question I dig into today is: Do artificial sweeteners affect the microbiome and in turn the  metabolic pathways* of the host? The short answer is yes, to both.


The push for non-nutritive sweeteners came from the idea that they taste sweet and the body does not metabolize them, so they can pass straight through.  However, research has shown multiple times that these sweeteners affect the microbiome by interacting with it and the metabolic pathways it regulates. (Bian 2017a and b, Sharma 2016, Suez 2014, Suez 2015, Swithers 2013, Tandel 2011)

The research is often the same, but it has been produced by several different labs.  For each project either rats, mice, or humans drinking water, sugar water or artificially sweetened water have been used as models. The studies range from short terms of a few days to long terms of 6 months.

The gut microbiome is affected

Through experiments, scientists showed that the metabolic dysregulation is caused by the change in the microbiome which is caused by the addition of artificial sweeteners to the diet. (Bian 2017a and b, Sharma 2016, Suez 2014, Suez 2015, Swithers 2013, Tandel 2011)

Saccharin is one of the most studied sweeteners. Saccharin alters the gut microbiome: decreasing the diversity of microbes in subjects who are drinking artificially-sweetened water. (Sharma 2016, Suez 2014, Suez 2015, Swithers 2013, Tandel 2011) Typically, an increase in Bacteroides and Clostridiales as well as a reduction in Lactobacilli, Firmicutes and other members of the Clostridiales are observed. (Suez 2014, Suez 2015) These changes in the microbiome parallels the microbiome of obese or diabetic mice and humans. (Suez 2015)

Additionally, by changing the microbiome, saccharin triggers an increase in pathways that enhance energy harvest. These pathways have been associated with obesity in mice and humans in separate studies. (Suez 2014)
Similarly to saccharin, Ace-K consumption significantly increased Bacteroides and decreased Lactobacillus and Clostridiales. (Bian 2017a)

Sucralose is one of the most used sweeteners. A study shows that 14 bacterial genera were altered with sucralose consumption. Specifically, 4 of these: Streptococcaceae Streptococcus, Dehalobacteriaceae Dehalobacterium, Lachnospiraceae Anaerostipes, and Lachnospiraceae Ruminoccocus, which are associated with anti-inflammatory activity, were found to be depleted in mice who drank sucralose water. (Bian 2017b) In addition to this, several genes related to bacterial pro-inflammatory mediators were elevated in mice who drank sucralose water. (Bian 2017b)

These changes create a new microbiome which dysregulates the host metabolism. Some bacteria that promote metabolic disorders find energy in the artificial sweeteners while other bacteria find it toxic and become depleted. Saccharin, sucralose and Ace-K have shown to affect the growth of specific bacteria.  Ace-K and saccharin affect intestinal bacteria responsible for glucose processing, when subjects consume Ace-K or saccharin, glucose fermentation is inhibited. (Bian 2017a, Suez 2015).

This picture sucralose passing through the colon and interacting with the microbiota by triggering bacterial toxins, proinflammatory metabolites and decreasing anti-inflammatory metabolites.
Sucralose interacts with the microbiome: it perturbs the gut microbiota and promotes inflammation and decreases the production of antiinflammatory compounds. (Figure 8. Bian 2017b)

The metabolic pathways of the host are also affected

As the subjects consume sweeteners such as saccharin, sucralose, aspartame, stevia, or ace K, each study provides the same results. Artificial sweetener consumption promotes unhealthy weight-gain. The response to glucose intake is lower and dysregulated, and there is an enhancement of the metabolic pathways associated with the metabolic syndrome such as poor insulin regulation and glucose metabolism. These conditions are similar to the health effects of type 2 diabetes and metabolic issues. The control subject, who consumed sugar water, did not see those results. (Bian 2017a, Sharma 2016, Suez 2014, Suez 2015, Swithers 2013, Tandel 2011)

Aspartame also promotes inflammation which can lead to type 2 diabetes. (Suez 2015) In human subjects specifically, BMI, blood pressure, hormonal and glycosylated hemoglobin (HbA1c) levels were also affected. (Sharma 2016, Suez 2014, Suez 2015) Also, liver damage and an increase in coronary heart disease risk were shown. (Suez 2014, Swithers 2013)

Some studies also consider the interaction of diet by testing the difference between a normal diet and a high-fat diet while the mice drink either sugar water (control) or water with saccharin. However, with either diet, as the mice drink artificially sweetened water, the same metabolic issues are present: i.e.  weight gain, poor glucose and insulin regulation.  (Suez 2014, Suez 2015)

In addition to specific measures, a long-term study showed an increase in coronary heart disease and kidney disease from consuming artificially sweetened soda compared to regular soda. (Sharma 2016)

My questions

The research on this subject is becoming more extensive, especially in the human subject realm. To further understand the problems arising from these sweeteners, it would be interesting to see a study taking humans off artificial sweeteners and observing changes in the microbiome and metabolic pathways. Does the microbiome revert back? How long does it take? Does it fully revert?

Finding a new alternative to sugar may not be the answer to weight management as the current alternatives prove to wreak havoc on our bodies and their microbiomes; and newer alternatives: sugar alcohols (xylitol, mannitol, sorbitol) also interact negatively with the gut microbiome. (Suez 2015)

Maybe a feasible return to healthy meals, meals made from using a variety of vegetables, starches and healthy proportions of proteins, carbs and fats, could be a better answer.

I think in a world where there are so many foods offered as a “healthy’ alternative, it’s important to understand what kind of alternative they truly provide.

Further reading

  • Ellen Ruppel shared in Scientific American the studies from an Israeli lab about the negative effects of the sweeteners
  • Alison Abbott wrote in Nature about a link between sugar substitutes and obesity.
  • Alexandra Sifferlin wrote in  Time  about the association of artificial sweeteners and weight gain.
  • The American Health Association and the American Diabetes Association both have voiced their concern regarding artificial sweeteners:  in Circulation.  
  • The Smithsonian also showed their concerns about sweeteners:
  • Stevia is often seen as a natural alternative, unfortunately it is part of the sweeteners under scrutiny. The Atlantic and The Daily Beast provide more information about it.
  • For more information on the metabolic syndrome here is some information from the American Heart Association.  


  • Bian, X., Chi, L., Gao, B., Tu, P., Ru, H., & Lu, K. (2017a). The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice. PLoS One, 12(6), e0178426. doi:10.1371/journal.pone.0178426
  • Bian, X., Chi, L., Gao, B., Tu, P., Ru, H., & Lu, K. (2017b). Gut Microbiome Response to Sucralose and Its Potential Role in Inducing Liver Inflammation in Mice. Front Physiol, 8, 487. doi:10.3389/fphys.2017.00487
  • Sharma, A., Amarnath, S., Thulasimani, M., & Ramaswamy, S. (2016). Artificial sweeteners as a sugar substitute: Are they really safe? Indian J Pharmacol, 48(3), 237-240. doi:10.4103/0253-7613.182888
  • Suez, J., Korem, T., Zeevi, D., Zilberman-Schapira, G., Thaiss, C. A., Maza, O., . . . Elinav, E. (2014). Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature, 514(7521), 181-186. doi:10.1038/nature13793
  • Suez, J., Korem, T., Zilberman-Schapira, G., Segal, E., & Elinav, E. (2015). Non-caloric artificial sweeteners and the microbiome: findings and challenges. Gut Microbes, 6(2), 149-155. doi:10.1080/19490976.2015.1017700
  • Swithers, S. E. (2013). Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends Endocrinol Metab, 24(9), 431-441. doi:10.1016/j.tem.2013.05.005
  • Tandel, K. R. (2011). Sugar substitutes: Health controversy over perceived benefits. J Pharmacol Pharmacother, 2(4), 236-243. doi:10.4103/0976-500X.85936