A placebo-controlled randomized trial in healthy adults found that commonly used dietary emulsifiers reduced key gut microbial metabolites but did not increase markers of intestinal or systemic inflammation over 4 weeks.
In the double-blind study conducted in Belgium and published in Clinical Gastroenterology and Hepatology, 58 participants first followed a two-week emulsifier-free diet, then were randomized to continue that diet while consuming brownies containing one of five emulsifiers or placebo for four additional weeks. The emulsifiers included carboxymethyl cellulose, polysorbate-80, carrageenan, soy lecithin, and native rice starch, according to Judith Wellens, MD, of the Translational Research Center for Gastrointestinal Disorders at KU Leuven in Belgium, and colleagues.
Emulsifiers were administered at doses approximating or exceeding typical dietary exposure, delivered within a food matrix to better reflect real-world intake. Outcomes included 16S ribosomal RNA sequencing, fecal short-chain fatty acids (SCFAs), permeability testing, and inflammatory and metabolic biomarkers.
The primary finding was a consistent reduction in fecal SCFAs among individuals receiving emulsifiers versus placebo. Reductions were most notable with carboxymethyl cellulose, which was associated with lower levels of acetic acid and butyric acid compared with placebo. Polysorbate-80 was linked to lower propionic acid levels. Across groups, regression analyses showed lower concentrations of all measured SCFAs with emulsifier exposure.
Despite these microbiome-related changes, inflammatory endpoints were unchanged. There were no differences between emulsifier groups and placebo in fecal calprotectin, C-reactive protein, or serum inflammatory proteomic markers at the end of the intervention. Similarly, no differences were observed in metabolic markers, including cholesterol, glucose, and insulin, during the supplementation phase.
One exception was intestinal permeability. Individuals consuming carrageenan showed an increase in transcellular permeability compared with baseline, although no between-group differences were observed versus placebo at study end.
The trial also evaluated the effects of eliminating emulsifiers before randomization. After two weeks on an emulsifier-free diet, total cholesterol decreased by about 10 mg/dL, with parallel reductions in high-density and low-density lipoprotein cholesterol. No changes were seen in inflammatory markers during this phase.
Microbiome analyses showed modest shifts. Alpha diversity increased slightly during the emulsifier-free phase but remained unchanged during emulsifier supplementation. However, overall microbial composition differed by treatment group and time point, indicating that emulsifiers influenced microbial structure even without altering diversity metrics.
The researchers acknowledged certain limitations of the study, including its small sample size and short duration. Also, participants were healthy, which may have reduced the chance of observing inflammatory effects. Diet adherence was self-reported, and the intervention also changed other aspects of diet, including calorie intake. In addition, the study examined single emulsifiers rather than the mixtures typically found in ultra-processed foods.
The findings suggest that emulsifiers may influence gut microbial metabolism without producing short-term inflammatory changes in healthy patients. A drop in SCFAs, compounds that help keep the gut lining healthy, may be an early or subtle change. This could be important to study further in people with inflammatory bowel disease or those at risk of developing it.
“These results point towards a beneficial influence of an emulsifier-free diet and possibly detrimental impact of specific emulsifiers on the gut-microbe interaction,” Dr. Wellens and her colleagues concluded.
The study was supported by the Research Foundation Flanders and other academic funding sources. Several authors reported consulting fees, research support, or speaking honoraria from pharmaceutical and nutrition-related companies.