A team of researchers led by Drs. Benoit Chassaing and Andrew T. Gewirtz of Georgia State University’s Institute for Biomedical Sciences have determined that a common food additive can aggravate development of serious intestinal illnesses.

The Georgia State scientists, working with colleagues at Emory University, Cornell University, and Bar-Ilan University in Israel, have found that emulsifiers, a class of additives used in most processed foods to improve texture and extend the product’s shelf life, also have the unhappy property of altering the composition of the large and diverse community of microbes collectively referred to as gut microbiota.

The emulsifiers have been shown capable of disrupting the gut ecosystem’s homeostasis of “good bacteria” and other microbial inhabitants of the gastrointestinal tract, and inducing intestinal inflammation that can initiate development of gut disorders like inflammatory bowel disease and metabolic syndrome.

Inflammatory bowel disease (IBD), a category that includes Crohn’s disease and ulcerative colitis, afflicts millions worldwide and is frequently severe and debilitating. Metabolic syndrome is a group of common obesity-related disorders that can lead to disorders like type-2 diabetes, and to cardiovascular and/or liver diseases. Incidence of IBD and metabolic syndrome has spiked upward markedly since the mid-20th Century.

The research on the effect of food additive emulsifiers was published Feb. 25 in Nature, in a paper entitled “Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome“ (Nature 519, 9296 (05 March 2015) doi:10.1038/nature14232) coauthored by Benoit Chassaing and Andrew T. Gewirtz of the Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University in Atlanta, Georgia; Omry Koren of the Bar Ilan University Faculty of Medicine at Safed, Israel; Julia K. Goodrich, Angela C. Poole, and Ruth E. Ley of the Cornell University Department of Molecular Biology and Genetics in Ithaca, New York; and Shanthi Srinivasan of the Emory University School of Medicine
Digestive Diseases Division at Atlanta, Georgia.

Environmental and dietary factors have been found to be significant contributors to gut pathogenesis that can progress to inflammatory disorders like the two aforementioned. In this paper, the authors find that mice on a diet containing emulsifying agents develop low-grade inflammation and obesity/metabolic syndrome. These conditions correlate with a decrease in gut microbiota-epithelial distance through degradation of mucus layers, altered species composition and pro-inflammatory potential.

The researchers note that the diverse population of roughly 100 trillion bacteria that we each carry as passengers in our intestinal tracts provide important benefits to as hosts, especially in their contributions to metabolism of nutrients and immune development. Unsurprisingly, disruption of the microbiota-host relationship is consequently associated with an array of chronic inflammatory diseases, including inflammatory bowel disease and the several obesity-associated diseases collectively categorized as metabolic syndrome.

Strictly speaking, the area inside the gastrointestinal tract extending from mouth to anus is still outside the human body’s internal systems, making the intestinal epithelium one of the body’s major interfaces with the outside world. The primary line of defense separating the bloodstream and lymphatic circulatory systems from gut microbiota is the multi-layered mucus structure that covers the intestinal lining, which when functioning properly keeps the vast majority of gut bacteria a safe distance from epithelial cells that line the intestine.

It’s therefore logical to deduce that agents acting to disrupt mucus-bacterial interactions would likely have potential to promote diseases associated with gut inflammation, and, it has been hypothesized that emulsifiers, “detergent-like molecules that are a ubiquitous component of processed foods,” can increase bacterial translocation across epithelia in vitro, and thus might be a major factor underlying increasing incidence of inflammatory bowel disease observed since the mid-twentieth century.

Since commencement of industrial scale addition of emulsifiers as food additives seemed to fit the time frame, and has been shown to promote bacterial translocation across epithelial cells, Drs. Chassaing and Gewirtz hypothesize that emulsifiers might affect the gut microbiota to promote these inflammatory diseases and designed experiments in mice to test this possibility.

In the Nature paper, the coauthors report that, in mouse model research it was found that even relatively low concentrations of two commonly-used emulsifiers frequently found on processed food ingredient labels — carboxymethylcellulose and polysorbate-80 — both have been found to induce low-grade inflammation and obesity/metabolic syndrome in wild-type hosts and to promote “robust” colitis in mice with a predisposition to that disorder.

Mice fed a diet containing emulsifying agents at doses seeking to model the broad consumption of the numerous emulsifiers that are incorporated into almost all processed foods were observed to develop low-grade inflammation and obesity/metabolic syndrome — conditions that correlate with diminishment of gut microbiotaepithelial distance caused by degradation they cause in the protective mucosal mucus, altered species composition and pro-inflammatory potential. The altered microbiota had enhanced capacity to digest and infiltrate the dense protective mucus layer that lines the intestine, which is normally, largely devoid of bacteria (sometimes referred to as “leaky gut syndrome”). Alterations in bacterial species resulted in bacteria expressing more flagellin and lipopolysaccharide, which can aggravate pro-inflammatory gene expression by the immune system.

“Emulsifier-induced metabolic syndrome” was also associated by the researchers with microbiota encroachment, altered species composition and increased pro-inflammatory potential. They report that use of germ-free mice, which lack a microbiota, and fecal transplants 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 played by the microbiota in mediating the adverse effect of emulsifiers.

The paper coauthors summarize that Drs. Chassaing and Gewirtz’s (et al.) findings suggest that emulsifiers might be partially responsible for this disturbance and for increased incidence of these diseases, and support emerging scientific awareness that disruption of normal host-microbiota interactions resulting in low-grade inflammation has the effect of promoting adiposity and associated metabolic effects. In addition, they suggest that broad use of emulsifying agents in processed foods may be contributing to an increased societal incidence of obesity/metabolic syndrome and other chronic inflammatory diseases. They conclude that since emulsifying agents are common food additives in the 21st-Century human diet, their findings suggest that further investigation into their potential impact on gut microbiota and human health is warranted.

The research team is now testing additional emulsifiers and designing experiments to investigate how emulsifiers affect humans. They propose that if similar results are obtained, that would further confirm the role this class of food additive is playing in driving the epidemic of obesity and its inter-related consequences including a range of diseases associated with chronic gut inflammation. They note that results of their study suggest that current means of testing and approving food additives may not be adequate to prevent use of chemicals that promote diseases driven by low-grade inflammation and/or which will cause disease primarily in susceptible hosts.

“A key feature of these modern plagues is alteration of the gut microbiota in a manner that promotes inflammation,” Dr. Gewirtz observes in a Georgia State release. His lab’s primary research interests include innate immunity, microbiome ecology, intestinal inflammation, and obesity/diabetes, and he notes that it is becoming increasingly apparent that inflammation plays a central role in many disease states including classic inflammatory diseases such as inflammatory bowel disease and chronic disorders such as obesity, type-2 diabetes, and cancer.

Dr. Gewirtz observes that considering the physiological role of most pro-inflammatory processes seems to be geared to protecting us against microbes, his research team’s goal is to understand the normal mechanisms by which pro-inflammatory signals protect against microbes, and to discern how they go awry in disease states.

The Gewirtz lab’s primary area of research focus is on the intestinal epithelium, which as noted above is one of the human body’s major interface boundaries with the outside world, and which while being very heavily colonized with Gram-negative bacteria, yet permits absorption of life-sustaining nutrients while protecting the tissues beneath from microbial onslaught. In addition to serving as a highly selective barrier, the intestinal epithelium regulates the microbial and immunological communities in its midst. Dr. Gewirtz notes that “specifically, the epithelia shapes the composition and locale of intestinal bacteria by producing antimicrobial substances and recruiting immune cells to efficiently clear bacteria that disturb equilibrium in the intestine. These pathways can go awry and result in chronic inflammation if the intestine inherits an aberrant microbial community and/or immune dysfunction.”

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

While fine details of the mechanisms that underly the effect of emulsifiers on human metabolism remain under study, the research team points 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,” Dr. Gewirtz explains. “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.”

The study was funded by the National Institutes of Health and the Crohns & Colitis Foundation of America.

Sources:
Georgia State University
Nature

Image Credits:
Georgia State University