While it has been long suggested that gut microbiota disturbances are involved in inflammatory bowel disease (IBD), obesity and metabolic syndrome, the new findings suggest emulsifiers might be partially responsible for this disturbance and the increased incidence of these diseases.
The study used mice to test the effect of two common emulsifiers - carboxymethylcellulose and polysorbate-80 - on the microbiome make up and metabolism, finding that relatively low-level concentrations of the emulsifiers resulted in distinct alterations to the gut microbial ecosystem (microbiota) and led to low-grade inflammation and the onset of metabolic syndrome.
Led by Dr Benoit Chassaing of Georgia State University, the research team reported that the emulsifier-induced metabolic syndrome was associated with microbiota encroachment, altered species composition and increased pro-inflammatory potential.
“These results support the emerging concept that perturbed host–microbiota interactions resulting in low-grade inflammation can promote adiposity and its associated metabolic effects,” wrote the team. “Moreover, they suggest that the broad use of emulsifying agents might be contributing to an increased societal incidence of obesity/metabolic syndrome and other chronic inflammatory diseases.”
However, Professor Tom Sanders of King’s College London warned that the study findings should not be a cause for concern - citing a major issue with the intake levels used in the study.
Sanders said the research team's conclusion that overeating in humans may be driven by food additives is 'headline grabbing and unwarranted', adding that "the fat, sugar and calories provided by ice-cream are far more likely to contribute to weight gain that trivial amounts of these additives.”
Indeed, the nutrition and diet expert added that the very high intake values used in the mouse study mean that it bears no impact for humans, as we only consume tiny amounts of any emulsifier ingredients in the foods we eat.
“This paper reports the effects in mice of very high intakes of two carbohydrate-based food additives (carboxymethyl cellulose E466 and polysorbate-80 E433)... Acceptable daily intakes (ADI) are expressed in mg/kg body weight and for E433 it is 10mg/kg body weight," noted Sanders. "A mouse weighs about 20g and drinks about 5 ml water a day, so an intake of 1% of these additives corresponds to an intake of 50mg/d or 2500 mg/kg."
"This is comparable to an intake 150,000 mg in a 60 kg adult which is 250 times greater than the ADI."
"The dramatic increase in these diseases [IBD, obesity and metabolic syndrome] has occurred despite consistent human genetics, suggesting a pivotal role for an environmental factor," commented Chassaing. "Food interacts intimately with the microbiota so we considered what modern additions to the food supply might possibly make gut bacteria more pro-inflammatory."
Chassaing and his colleagues theorised that emulsifiers might affect the gut microbiota to promote these inflammatory diseases and designed experiments in mice to test this possibility.
Mice were fed two commonly used emulsifiers, polysorbate 80 and carboxymethylcellulsose, at doses seeking to model the broad consumption of the numerous emulsifiers that are incorporated into almost all processed foods, they said.
The team found that emulsifier consumption changed the species composition of the gut microbiota - and did so in a manner that made it more pro-inflammatory.
According to the team, the altered microbiota had enhanced capacity to digest and infiltrate the dense mucus layer that lines the intestine, which is normally, largely devoid of bacteria.
In addition, alterations in bacterial species resulted in bacteria expressing more flagellin and lipopolysaccharide, which can activate pro-inflammatory gene expression by the immune system, said Chassaing and colleagues.
These changes in bacterial expression triggered chronic colitis in mice genetically prone to this disorder, revealed the team.
In contrast, in mice with normal immune systems, emulsifiers induced low-grade or mild intestinal inflammation and metabolic syndrome, characterized by increased levels of food consumption, obesity, hyperglycemia and insulin resistance.
However, the effects of emulsifier consumption were eliminated in germ-free mice, which lack a microbiota, said the team. Who also showed that transplant of the microbiota from emulsifiers-treated mice to germ-free mice was enough to transfer some parameters of low-grade inflammation and metabolic syndrome.
Chassaing and his team said this indicates that the microbiota has a ‘central role’ in mediating the adverse effect of emulsifiers.
The team is now testing additional emulsifiers and designing experiments to investigate how emulsifiers affect humans.
If similar results are obtained, it would indicate a role for the food additive in driving the epidemic of obesity, its inter-related consequences and a range of diseases associated with chronic gut inflammation, said the authors.
While detailed mechanisms underlying the effect of emulsifiers on metabolism remain under study, Chassaing and co pointed out that avoiding excess food consumption is of paramount importance.
"We do not disagree with the commonly held assumption that over-eating is a central cause of obesity and metabolic syndrome," said Andrew Gewirtz, senior author of the study. “Rather, our findings reinforce the concept suggested by earlier work that low-grade inflammation resulting from an altered microbiota can be an underlying cause of excess eating."
Published online ahead of print, doi: 10.1038/nature14232
“Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome”
Authors: Benoit Chassaing, et al