Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome
Open accessAbstract
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.
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Administration of two dietary emulsifiers, polysorbate-80 and carboxymethyl cellulose, induced obesity, intestinal inflammation, and metabolic dysfunction in mice in the absence of other dietary manipulations.
“administration of two dietary emulsifiers, polysorbate-80 and carboxymethyl cellulose, induced obesity, intestinal inflammation, and metabolic dysfunction in the absence of other dietary manipulations in mice.”
From The gut microbiota at the intersection of diet and human health (2018) · cites this paper as [55]
The doses of emulsifiers used in the study are well within the amount consumed by humans.
“the doses used in the study are well within the amount consumed by humans.”
From The gut microbiota at the intersection of diet and human health (2018) · cites this paper as [55]
The microbiota was both required and sufficient for these emulsifier-induced effects: germ-free mice were protected, and microbiota transfer from emulsifier-treated mice recapitulated the metabolic derangements.
“The microbiota was both required and sufficient for these effects as GF mice were protected from detrimental consequences, and microbiota transfer from emulsifier-treated mice was sufficient to recapitulate the metabolic derangements (55).”
From The gut microbiota at the intersection of diet and human health (2018) · cites this paper as [55]
Emulsifiers and artificial sweeteners can promote metabolic syndrome features in mice by modulating the microbiota.
“Emulsifiers and artificial sweeteners have been shown to be involved in the development of metabolic syndrome features through their modulation of the microbiota in mice46,47.”
From Diet–microbiota interactions as moderators of human metabolism (2016) · cites this paper as [46]
Emulsifier feeding shifts gut microbiome composition, decreasing Bacteroidales and increasing mucolytic bacteria such as Ruminococcus gnavus.
“The composition of the gut microbiome was also impacted with decreased abundances of the Bacteroidales (phylum: Bacteroidetes) and increased levels of mucolytic bacteria, such as Ruminococcus gnavus135.”
From The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism (2016) · cites this paper as [135]
Emulsifiers failed to produce these effects in germ-free mice.
“Interestingly, emulsifiers failed to have this effect on germ-free mice.”
From The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism (2016) · cites this paper as [135]
Emulsifier-induced shifts in microbial community structure are accompanied by low-grade inflammation, increased gut permeability, increased weight and adiposity, and development of metabolic syndrome.
“These shifts in microbial community structure were accompanied by low-grade inflammation, increased gut permeability, increased weight and adiposity, and development of metabolic syndrome.”
From The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism (2016) · cites this paper as [135]
Feeding mice the emulsifiers carboxymethylcellulose and polysorbate-80 reduces intestinal mucus thickness and increases microbial encroachment toward epithelial cells.
“Controlled feeding of two emulsifying agents, carboxymethylcellulose and polysorbate-80 (Tween 80), to mice resulted in a reduction of the thickness of intestinal mucus and, as a result, microbial cells showed increased encroachment towards epithelial cells135.”
From The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism (2016) · cites this paper as [135]
Emulsifier feeding of genetically sensitized mice prone to inflammation promoted a colitis phenotype.
“emulsifier feeding of genetically sensitized animals that are prone to inflammation (Il10−/− and Tlr5−/− mice) promoted a colitis phenotype.”
From The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism (2016) · cites this paper as [135]
This suggests that the composition of the gut microbiota is a key driver of metabolic syndrome and low-grade inflammation.
“This suggests that the composition of the gut microbiota is a key driver of metabolic syndrome and low-grade inflammation.”
From The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism (2016) · cites this paper as [135]
Emulsifier consumption by germ-free animals and animals with a highly restricted microbiota did not elicit the same detrimental health effects, suggesting that microbial modulation may be required for the adverse effects of emulsifiers on host health.
“Importantly, it has been shown that emulsifier consumption by germ-free (GF) animals (107) and animals with a highly restricted microbiota (180) did not elicit the same detrimental health effects, suggesting that microbial modulation may be required for the adverse effects of emulsifiers on host health.”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [107]
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- Authors
- Chassaing, B., Koren, O., Goodrich, J. K., Poole, A. C., Srinivasan, S., Ley, R. E., & Gewirtz, A. T.
- Affiliations
- Bar-Ilan University (IL)
- Cornell University (US)
- Emory University (US)
- Georgia State University (US)
- Corresponding author
- Gewirtz, Andrew T.
- Venue
- Nature
- Published
- 2015-02-25
- Volume
- 519
- Issue
- 7541
- Pages
- 92-96
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4910713
- OpenAlex
- W2134657806
- Cited by
- 2,055
- References
- 45
- Citations by year
- 2026: 163 · 2025: 193 · 2024: 207 · 2023: 192 · 2022: 234 · 2021: 209 · 2020: 226 · 2019: 177 · 2018: 142 · 2017: 152 · 2016: 109 · 2015: 49
- FWCI
- 65.35
- Type
- journal article
- Language
- en
- Update notices
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Crohn's and Colitis Foundation (276509)
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (U24DK097153, DK083890, DK099071, R01DK099071, R01DK083890)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Microbial Metabolites in Food Biotechnology
- Keywords
- food emulsifiers, gut microbiota, colitis, metabolic syndrome, obesity, low-grade inflammation, carboxymethyl cellulose, Tween 80, inflammatory bowel disease, germ-free mice, fecal microbiota transplantation, food additives, adiposity, intestinal barrier integrity, pro-inflammatory bacteria
- MeSH terms
- Animals, Carboxymethylcellulose Sodium, Colitis, Diet, Feces, Female, Germ-Free Life, Inflammation, Intestinal Mucosa, Male, Obesity, Polysorbates, Metabolic Syndrome, Gastrointestinal Tract, Emulsifying Agents, Adiposity, Mice, Microbiota
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