In the JournalsPerspective

Artificial sweetener Splenda may worsen IBD symptoms

The artificial sweetener Splenda promoted microbial dysbiosis and Crohn’s-like disease in genetically susceptible mice, suggesting that consumption of this product could exacerbate symptoms in patients with Crohn’s disease, according to new research published in Inflammatory Bowel Diseases.

“Our findings suggest that patients with Crohn’s disease should think carefully about consuming Splenda or similar products containing sucralose and maltodextrin,” study author Alex Rodriguez-Palacios, DVM, MSc, DVSc, PhD, assistant professor of medicine at Case Western Reserve School of Medicine, said in a press release. “This study demonstrates that the sweetener induces changes in gut bacteria and gut wall immune cell reactivity, which could result in inflammation or disease flare ups in susceptible people. On the other hand, the study suggests that individuals free of intestinal diseases may not need to be overly concerned.”

While prior studies have separately tested Splenda’s ingredients — the artificial sweetener sucralose, which is believed to be indigestible, and the digestible sweetener maltodextrin — Rodriguez-Palacios and colleagues tested them in combination in what he called “one of the best animal models of ileal Crohn’s disease.”

After 6 weeks of Splenda exposure in both ileitis-prone and healthy mice, the researchers observed increased Proteobacteria in all mice, but within that phylum, E. coli increased and penetrated into the ileal lamina propria of the ileitis-prone mice only.

Further, the ileitis-prone mice showed increased intestinal activity of the pro-inflammatory enzyme myeloperoxidase, likely in response to the increased presence of E. coli, the researchers concluded.

They said the findings suggest that Splenda consumption may increase the production of pro-inflammatory myeloperoxidase in individuals who are susceptible to inflammatory bowel disease, and could exacerbate symptoms in patients with Crohn’s disease. This, they added, would be consistent with reports that artificial sweeteners worsen symptoms in 10% to 15% of IBD patients.

They also noted that Proteobacteria and myeloperoxidase might be used as fecal biomarkers to monitor how patients adjust to dietary changes.

“This is perhaps the closest we can get to provide experimental evidence that these ingredients together induce biological changes known to cause inflammation, which could be harmful over time to susceptible animal subjects,” Rodriguez-Palacios said in the press release. “Our next step would be to run experiments directly in patients, but that is more difficult to conduct given the large variability that is inherent to human genetics, microbiome and diet.”

The findings also suggest that other dietary factors could cause similar changes to the gut microbiota that exacerbate IBD symptoms, according to study co-author Fabio Cominelli, MD, PhD, professor of medicine, at Case Western Reserve School of Medicine and chief of gastroenterology at UH Cleveland Medical Center.

“Our findings were due solely to the administration of a minor component of the diet,” he said in the press release. “This suggests that other dietary habits or additives may lead to similar microbiota alterations. For instance, diet emulsifiers used as food additives have also been shown recently to alter the gut microbiota and promote colitis in mice. Other scenarios could put Crohn’s disease patients at risk of having exaggerated inflammation as well. This could include unexpected foodborne bacterial infections, which would further recruit myeloperoxidase-containing leukocytes to the intestinal tract and the resultant inflammation.”

In a related editorial, Benoit Chassaing, PhD, and Andrew T. Gewirtz, PhD, both from the Center for Inflammation, Immunity and Infection, at Georgia State University’s Institute for Biomedical Sciences, called this study “critically important,” and called for similarly designed studies to be considered in “FDA testing of food additives designed to detect chronic and low-grade inflammation and consider impacts on the gut microbiota.” – by Adam Leitenberger

Disclosures: The authors report no relevant financial disclosures.

Emerging data continue to reveal how diet may interact with the gut microbiome in ways that affect IBD symptoms. Below, you can read about 6 other recent developments in this area of research previously reported by Healio Gastroenterology and Liver Disease.

1. Fatty acid linked to increased risk for UC flare in mesalamine-treated patients

High consumption of certain fatty acids, including myristic fatty acid found in dairy fat and coconut oil, was found to be associated with an increased risk for relapse in patients with ulcerative colitis who were treated with mesalamine, according to data presented at DDW 2016. Read more

2. Dietary fiber associated with reduced Crohn’ s disease flares

Researchers suggested re-evaluating recommendations to limit dietary fiber due to recent evidence that disease flares in patients with Crohn’s disease may be reduced with the intake of dietary fiber. However, in the study, the reduced flares were not observed in patients with ulcerative colitis. Read more

3. Specific carbohydrate diet shows promise in pediatric IBD

Children with Crohn’s disease and ulcerative colitis achieved clinical remission after specific carbohydrate diet therapy, according to the results of a small prospective study. Read more

4. Diet in IBD: An important component to stabilize the microbiome

While diet may be used as primary or adjunctive therapy, it is an important part of addressing almost any disease process, according to David L. Suskind, MD, professor of pediatrics and director of clinical gastroenterology at Seattle Children’s Hospital. Read more

5. Microbiome research aims to uncover how diet can treat IBD

In this exclusive video from the Crohn’s & Colitis Congress, Gary Wu, MD, of University of Pennsylvania, discusses his presentation on the intersection between diet, the microbiome and inflammatory bowel disease, and the potential of more well-defined diets to treat the disease. Watch here

6. Nutrition therapy for pediatric IBD continues to advance

In this exclusive video from Advances in IBD 2017, David L. Suskind, MD, professor of pediatrics and director of clinical gastroenterology at Seattle Children’s Hospital, University of Washington, discusses recent advances in the use of nutrition therapy in pediatric inflammatory bowel disease. Watch here

The artificial sweetener Splenda promoted microbial dysbiosis and Crohn’s-like disease in genetically susceptible mice, suggesting that consumption of this product could exacerbate symptoms in patients with Crohn’s disease, according to new research published in Inflammatory Bowel Diseases.

“Our findings suggest that patients with Crohn’s disease should think carefully about consuming Splenda or similar products containing sucralose and maltodextrin,” study author Alex Rodriguez-Palacios, DVM, MSc, DVSc, PhD, assistant professor of medicine at Case Western Reserve School of Medicine, said in a press release. “This study demonstrates that the sweetener induces changes in gut bacteria and gut wall immune cell reactivity, which could result in inflammation or disease flare ups in susceptible people. On the other hand, the study suggests that individuals free of intestinal diseases may not need to be overly concerned.”

While prior studies have separately tested Splenda’s ingredients — the artificial sweetener sucralose, which is believed to be indigestible, and the digestible sweetener maltodextrin — Rodriguez-Palacios and colleagues tested them in combination in what he called “one of the best animal models of ileal Crohn’s disease.”

After 6 weeks of Splenda exposure in both ileitis-prone and healthy mice, the researchers observed increased Proteobacteria in all mice, but within that phylum, E. coli increased and penetrated into the ileal lamina propria of the ileitis-prone mice only.

Further, the ileitis-prone mice showed increased intestinal activity of the pro-inflammatory enzyme myeloperoxidase, likely in response to the increased presence of E. coli, the researchers concluded.

They said the findings suggest that Splenda consumption may increase the production of pro-inflammatory myeloperoxidase in individuals who are susceptible to inflammatory bowel disease, and could exacerbate symptoms in patients with Crohn’s disease. This, they added, would be consistent with reports that artificial sweeteners worsen symptoms in 10% to 15% of IBD patients.

They also noted that Proteobacteria and myeloperoxidase might be used as fecal biomarkers to monitor how patients adjust to dietary changes.

“This is perhaps the closest we can get to provide experimental evidence that these ingredients together induce biological changes known to cause inflammation, which could be harmful over time to susceptible animal subjects,” Rodriguez-Palacios said in the press release. “Our next step would be to run experiments directly in patients, but that is more difficult to conduct given the large variability that is inherent to human genetics, microbiome and diet.”

The findings also suggest that other dietary factors could cause similar changes to the gut microbiota that exacerbate IBD symptoms, according to study co-author Fabio Cominelli, MD, PhD, professor of medicine, at Case Western Reserve School of Medicine and chief of gastroenterology at UH Cleveland Medical Center.

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“Our findings were due solely to the administration of a minor component of the diet,” he said in the press release. “This suggests that other dietary habits or additives may lead to similar microbiota alterations. For instance, diet emulsifiers used as food additives have also been shown recently to alter the gut microbiota and promote colitis in mice. Other scenarios could put Crohn’s disease patients at risk of having exaggerated inflammation as well. This could include unexpected foodborne bacterial infections, which would further recruit myeloperoxidase-containing leukocytes to the intestinal tract and the resultant inflammation.”

In a related editorial, Benoit Chassaing, PhD, and Andrew T. Gewirtz, PhD, both from the Center for Inflammation, Immunity and Infection, at Georgia State University’s Institute for Biomedical Sciences, called this study “critically important,” and called for similarly designed studies to be considered in “FDA testing of food additives designed to detect chronic and low-grade inflammation and consider impacts on the gut microbiota.” – by Adam Leitenberger

Disclosures: The authors report no relevant financial disclosures.

Emerging data continue to reveal how diet may interact with the gut microbiome in ways that affect IBD symptoms. Below, you can read about 6 other recent developments in this area of research previously reported by Healio Gastroenterology and Liver Disease.

1. Fatty acid linked to increased risk for UC flare in mesalamine-treated patients

High consumption of certain fatty acids, including myristic fatty acid found in dairy fat and coconut oil, was found to be associated with an increased risk for relapse in patients with ulcerative colitis who were treated with mesalamine, according to data presented at DDW 2016. Read more

2. Dietary fiber associated with reduced Crohn’ s disease flares

Researchers suggested re-evaluating recommendations to limit dietary fiber due to recent evidence that disease flares in patients with Crohn’s disease may be reduced with the intake of dietary fiber. However, in the study, the reduced flares were not observed in patients with ulcerative colitis. Read more

3. Specific carbohydrate diet shows promise in pediatric IBD

Children with Crohn’s disease and ulcerative colitis achieved clinical remission after specific carbohydrate diet therapy, according to the results of a small prospective study. Read more

4. Diet in IBD: An important component to stabilize the microbiome

While diet may be used as primary or adjunctive therapy, it is an important part of addressing almost any disease process, according to David L. Suskind, MD, professor of pediatrics and director of clinical gastroenterology at Seattle Children’s Hospital. Read more

5. Microbiome research aims to uncover how diet can treat IBD

In this exclusive video from the Crohn’s & Colitis Congress, Gary Wu, MD, of University of Pennsylvania, discusses his presentation on the intersection between diet, the microbiome and inflammatory bowel disease, and the potential of more well-defined diets to treat the disease. Watch here

6. Nutrition therapy for pediatric IBD continues to advance

In this exclusive video from Advances in IBD 2017, David L. Suskind, MD, professor of pediatrics and director of clinical gastroenterology at Seattle Children’s Hospital, University of Washington, discusses recent advances in the use of nutrition therapy in pediatric inflammatory bowel disease. Watch here

    Perspective
    David L. Suskind

    David L. Suskind

    From a clinician’s point of view, this study emphasizes the impact of diet on the microbiome and likely on clinical activity. One of the main take-home points from the paper is that Splenda itself increased a phylum of bacteria called Proteobacteria that includes E. coli, which is one of the organisms that is implicated in inflammatory bowel disease. This adds to the existing data and sheds more light on the impact of food on the microbiome and subsequently IBD.

    In human studies, it’s difficult to focus on the effect of one additive or one food type, however, this is not the case with animal models. We find in patients with IBD that there is an amalgamation of impact from all the different foods consumed.  In animal models, we can observe a slice of the impact by isolating one additive at a time. The impact of products like Splenda on the microbiome in conjunction with many other foods and food additives are the key to why we’re seeing so much more IBD and these insights allow us to better define our nutritional treatments for our patients.

    The implication of food additives in the diet has been poorly studied and this includes the impact of these food additives on the well-being of patients with IBD. Only recently have researchers begun to examine food additives’ effect on the microbiome and diseases such as IBD. Because additives such as Splenda and emusifiers, are not essential, we have recommend patients avoid them as much as possible. An ounce of prevention is worth a pound of cure.

    • David L. Suskind, MD
    • Professor of Pediatrics Division of Gastroenterology, Hepatology and Nutrition Seattle Children's Hospital University of Washington

    Disclosures: Suskind reports no relevant financial disclosures.

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