The team fed mice 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 observed that emulsifier consumption changed the species composition of the gut microbiota and did so in a manner that made it more pro-inflammatory.
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. Alterations in bacterial species resulted in bacteria expressing more flagellin and lipopolysaccharide, which can activate pro-inflammatory gene expression by the immune system.
Bacteria that are present deeper in the mucus layer that lines the intestine and closer to the epithelium than they should be. Credit: Dr. Benoit Chassaing
Such changes in bacteria triggered chronic colitis in mice genetically prone to this disorder, due to abnormal immune systems. 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.
Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, afflicts millions of people and is often severe and debilitating. Metabolic syndrome is a broadly-defined group of obesity-related disorders that may lead to type-2 diabetes, cardiovascular and/or liver diseases. Incidence of IBD and metabolic syndrome has been markedly increasing since the mid-20th century and the authors correlate emulsifiers to that. Addition of emulsifiers to food seemed to fit the time frame and had been shown to promote bacterial translocation across epithelial cells. The authors set out to show that emulsifiers might affect the gut microbiota to promote these inflammatory diseases and designed experiments in mice to test this possibility.
The term "gut microbiota" refers to the diverse population of 100 trillion bacteria that inhabit the intestinal tract. Gut microbiota are disturbed in IBD and metabolic syndrome.
The effects of emulsifier consumption were eliminated in germ-free mice, which lack a microbiota. Transplant of microbiota from emulsifiers-treated mice to germ-free mice was sufficient to transfer some parameters of low-grade inflammation and metabolic syndrome, indicating a central role for the microbiota 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 this class of food additive in driving the epidemic of obesity, its inter-related consequences and a range of diseases associated with chronic gut inflammation.
Funded by the National Institutes of Health and Crohn's&Colitis Foundation of America. Published in Nature.
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