Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome.
The intestinal tract is inhabited by a large and diverse community of microbes collectively referred to as the gut microbiota. While the gut microbiota provides important benefits to its host, especially in metabolism and immune development, disturbance of the microbiota-host relationship is associated with numerous chronic inflammatory diseases, including inflammatory bowel disease and the group of obesity-associated diseases collectively referred to as metabolic syndrome. A primary means by which the intestine is protected from its microbiota is via multi-layered mucus structures that cover the intestinal surface, thereby allowing the vast majority of gut bacteria to be kept at a safe distance from epithelial cells that line the intestine. Thus, agents that disrupt mucus-bacterial interactions might have the potential to promote diseases associated with gut inflammation. Consequently, it has been hypothesized that emulsifiers, detergent-like molecules that are a ubiquitous component of processed foods and that can increase bacterial translocation across epithelia in vitro, might be promoting the increase in inflammatory bowel disease observed since the mid-twentieth century. Here we report that, in mice, relatively low concentrations of two commonly used emulsifiers, namely carboxymethylcellulose and polysorbate-80, induced low-grade inflammation and obesity/metabolic syndrome in wild-type hosts and promoted robust colitis in mice predisposed to this disorder. Emulsifier-induced metabolic syndrome was associated with microbiota encroachment, altered species composition and increased pro-inflammatory potential. Use of germ-free mice and faecal transplants indicated that such changes in microbiota were necessary and sufficient for both low-grade inflammation and metabolic syndrome. These results support the emerging concept that perturbed host-microbiota interactions resulting in low-grade inflammation can promote adiposity and its associated metabolic effects. 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.
Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia 30303, USA.
Benoit
B
Chassaing
Faculty of Medicine, Bar Ilan University, Safed, 13115, Israel.
Omry
O
Koren
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
Julia K
JK
Goodrich
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
Angela C
AC
Poole
Digestive Diseases Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Shanthi
S
Srinivasan
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
Ruth E
RE
Ley
Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia 30303, USA.
Andrew T
AT
Gewirtz
D050154:Adiposity / Q000187:drug effects; D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage / Q000009:adverse effects; D003092:Colitis / Q000139:chemically induced* / Q000382:microbiology* / Q000473:pathology; D004032:Diet / Q000009:adverse effects*; D045703:Emulsifying Agents / Q000008:administration & dosage / Q000009:adverse effects*; D005243:Feces / Q000382:microbiology; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000382:microbiology* / Q000473:pathology; D005856:Germ-Free Life; D007249:Inflammation / Q000139:chemically induced / Q000382:microbiology / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced* / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D064307:Microbiota / Q000187:drug effects; D009765:Obesity / Q000139:chemically induced / Q000382:microbiology / Q000473:pathology; D011136:Polysorbates / Q000008:administration & dosage / Q000009:adverse effects
D045703:Emulsifying Agents; D011136:Polysorbates; D002266:Carboxymethylcellulose Sodium