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US National Institutes of Health: Food additives can alter gut microbes and cause diseases (2015-03-18)

Emulsifiers, which are added to most processed foods to aid texture and extend shelf life, can alter the gut microbiota composition and localization to induce intestinal inflammation that promotes the development of inflammatory bowel disease and metabolic syndrome, new research shows.

The research, published Feb. 25 in Nature, was led by Georgia State University Institute for Biomedical Sciences’ researchers Drs. Benoit Chassaing and Andrew T. Gewirtz, and included contributions from Emory University, Cornell University and Bar-Ilan University in Israel.


Mice fed emulsifiers had bacteria (red) deep in the mucus layer (green) so they were closer to intestinal cells (purple and blue) than they should be. Image by the researchers.

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 group of very common obesity-related disorders that can 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.

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. Chassaing and Gewirtz’s findings suggest emulsifiers might be partially responsible for this disturbance and the increased incidence of these diseases.

“A key feature of these modern plagues is alteration of the gut microbiota in a manner that promotes inflammation,” says Gewirtz.

“The dramatic increase in these diseases has occurred despite consistent human genetics, suggesting a pivotal role for an environmental factor,” says 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.”

Addition of emulsifiers to food seemed to fit the time frame and had been shown to promote bacterial translocation across epithelial cells. Researchers hypothesized that emulsifiers might affect the gut microbiota to promote these inflammatory diseases and designed experiments in mice to test this possibility.

Dietary emulsifiers are added to many processed foods to improve texture and extend shelf life. Chemically similar to detergents, they have been shown to alter the mucus barrier and the microbes associated with it.

To determine whether these might play a role in chronic diseases, the team fed mice low levels of 2 commonly used emulsifiers, carboxymethylcellulose or polysorbate-80, in drinking water or in food 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.

Mice fed the emulsifiers for 12 weeks developed low-grade intestinal inflammation and metabolic syndrome characterized by increased levels of food consumption, obesity, hyperglycemia and insulin resistance, a group of conditions that increase the risk for type 2 diabetes, heart disease, and stroke.
Mice that were genetically engineered to be more prone to inflammation and gut microbe changes developed colitis when fed the emulsifiers.

Mice that consumed the emulsifiers had an altered bacterial composition and thinner intestinal mucus, so that bacteria were closer to the cells lining the colon. The mice also had weight gain, increased food consumption, increased fat mass, and impaired glucose handling, a sign of metabolic syndrome.

When the team fed emulsifiers to germ-free mice, which don’t have gut microbiota, the mice showed no signs of gut inflammation, mucus thinning, or metabolic syndrome.
This suggests that the effects of the emulsifiers were most likely caused by altering gut bacteria.

When gut microbes from normal, emulsifier-fed mice were transplanted into germ-free mice that hadn’t been fed emulsifiers, the mice developed low grade inflammation, increased fat mass, and glucose intolerance. These results showed that changes in the gut microbiota caused by dietary emulsifiers can drive inflammation and metabolic changes.

“We do not disagree with the commonly held assumption that over-eating is a central cause of obesity and metabolic syndrome,” Gewirtz says. But these results suggest that modern additions to the food supply can interact with gut microbiota to influence inflammation, metabolism, and weight.

The group is now testing additional emulsifiers. They are also designing experiments to examine the effects of food additives in humans.

The research was funded in part by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Findings appeared in Nature on March 5, 2015.

For more information
Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Chassaing B, Koren O, Goodrich JK, Poole AC, Srinivasan S, Ley RE, Gewirtz AT. Nature. 2015 Mar 5;519(7541):92-6. doi: 10.1038/nature14232. Epub 2015 Feb 25. PMID: 25731162.

Georgia State University

US National Institutes of Health (NIH)

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