Evidence of harm
Dr. Lewis noted that in 2013, investigators at the University of Liverpool, England, published a hypothesis suggesting that consumption of emulsifiers in processed foods may promote Crohn’s disease by increasing bacterial translocation. Their hypothesis was based in part on evidence that “very small concentrations of the emulsifier polysorbate 80 enhance bacterial translocation across intestinal epithelia. Undigested emulsifiers may increase bacterial translocation, particularly in the small intestine where the mucus layer is discontinuous. “
The authors also suggested that their hypothesis could be tested in clinical trials comparing enteral feeding with and without emulsifiers.
Other suggestive if not definitive evidence of a potential link between additives and IBD are data showing that IBD is very rare in young children.
“In your early stages of your life, you’re not consuming a lot of ultraprocessed foods. Indeed, the rate of intake of at least fast foods, which you can think of almost as a surrogate for ultraprocessed foods, goes up dramatically when people get to their teens, and this is the same time as we see, really, the big uptick in the incidence of IBD,” Dr. Lewis said.
A link between ultraprocessed food consumption and later development of IBD, primarily Crohn’s disease, is also suggested by data from the Nurses Health Study I and II and Health Professionals Follow-Up study. Among 245,112 participants with about 5.5 million person-years of follow-up, the highest vs. lowest quartile of consumption of ultraprocessed foods was associated with a 70% increase in risk for developing Crohn’s (hazard ratio 1.70, P = .0008).
Animal studies
Evidence for a possible mechanism whereby emulsifiers and thickeners cause intestinal changes comes from a study published in Nature in 2015 showing that adding CMC and PS80 to the drinking water of mice resulted in major shifts in the gut microbiota in both wild-type and interleukin 10 knockout mice, a model for IBD.
When the additives were put into the water the mice had a thinning of the mucus layer, allowing bacteria in closer proximity to the epithelium.
“When you put these into the drinking water of IL-10 knockout mice that are already predisposed to developing colitis, they were far more likely to go on to develop colitis over the course of 3 months,” Dr. Lewis said.
From mouse to man
Dr. Lewis briefly summarized results of the FRESH study that he and colleagues recently published in Gastronterology. In this trial, 16 healthy adult volunteers who agreed to stay and eat all meals at the research center were randomized to receive either an emulsifier-free diet or the identical diet enriched with 15 g of CMC daily for 11 days.
“I will comment that that’s a lot of carboxymethycellulose,” Dr. Lewis said.
The volunteers fed the CMC-enriched diet had a slight increase in abdominal discomfort after eating and a reduction in species diversity in the gut microbiota. In addition, these participants had reductions in levels of short-chain fatty acids and free amino acids, both of which are signs of a health gut environment.
“Furthermore, we identified 2 subjects consuming CMC who exhibited increased microbiota encroachment into the normally sterile inner mucus layer, a central feature of gut inflammation, as well as stark alterations in microbiota composition,” the investigators wrote.
Dr. Lewis cited a separate small study by investigators at the University of Illinois at Chicago and the University of Chicago. These investigators randomized patients with UC in remission to take supplements containing carrageenan – a seaweed-derived food additive that has been shown to cause inflammation in both in vitro and animal models – or placebo . The amount of carrageenan in the capsules was less than that found in an average daily Western diet, the authors noted.
The participants were followed with telephone calls every 2 weeks or until relapse, which was defined as an increase of 2 or more points on the Simple Clinical Colitis Activity Index (SCCAI) and intensification of treatment for UC.
Of the 12 patients who completed the study, 3 in the carrageenan group experienced relapses, compared with none of the patients in the placebo group (P = .046). The relapse occurred at 5, 32, and 42 weeks of follow-up.