Feeding mice with artifical emulsifiers impacts their metabolism
Snap-shot of the study
Emulsifiers are used extensively in the food we eat (ice creams, biscuits etc.). This study examines the effect of feeding mice emulsifiers both in their food and drink (5).
Mice fed on emulsifiers (Carboxymethylycellulose CMC and Polysorbate P-80) showed increased appetite. They also showed signs of low-grade inflammation in the gut and increased fat deposition. The authors attribute these effects to changes in the gut microbiota. While the number of microorganisms in the gut was not altered by diet containing emulsifiers, the kinds of microbiota were completely different. The mucus lining was also depleted and the microbes were closer to the cells in the gut, possibly causing the inflammation. While this study has been done on mice, perhaps the quality and quantity of our microbiota and their response to emulsifiers has some bearing for us too.
What did they do?
They added widely used emulsifiers- Carboxymethyl cellulose (E466) and Polysorbate-80 (E433) to the food and drinking water of young mice at equivalent concentrations commonly used in human food.
They measured the abundance and diversity of the gut microbiota, inflammation of the gut (colitis) and also metabolic disorders (fat accumulation, increase in food intake and fasting blood sugar levels) in the emulsifier-fed mice and compared to control mice (no emulsifier in food or drink)
What did they find?
These mice (treated) had same number of bacteria (in their gut) compared to mice that were not fed emulsifier (control mice). The types of microbes however was quite different. The microbes were also found closer to the gut that in control mice. The treated mice showed increased appetite, followed by fat deposition and low grade inflammation of the gut. Interestingly, transplantation of the microorganisms of the gut from emulsifier fed animals into germ-free mice also resulted in increased fat deposition and inflammation of the gut. Suggesting that changes in the microbiota caused by the emulsifiers may be sufficient to cause the metabolic dysfunction and observed inflammation.
Erosion of the protective mucosal layer around gut epithelium in emulsifier-fed mice resulting in reducing the separation between the microbiota and the gut epithelium. Emulsifiers caused a marked change in gut microbiota composition – Higher pro-inflammatory microbiota including the bacterial species that are the leading cause of colitis like Bilophila and Helicobacter. Changed gut microbiota in emulsifier-fed mice increased gut inflammation and colitis. Emulsifier-fed mice also show – dysregulation of blood sugar levels (mild diabetes), increased food consumption correlated with increased adiposity(fat deposition) and weight gain. In older mice (4 months old) the changes persisted for more that 6 weeks even after emulsifiers were stopped. The observed effects of emulsifiers are exclusively due to the change in gut microbiota as the emulsifiers did not show any effect in mice having no gut microbiota (germ free mice). Interestingly such germ free mice become labile to the effects of the emulsifiers if the regular gut microbiome is reintroduced in them.
Background to the study
An undisturbed gut flora is emerging as an important factor in health versus disease (1). Multiple different physiological conditions including obesity and type 2 Diabetes are now associated with changes in the gut microflora (2-3). Recent studies have found that artificial sweeteners can cause blood sugar related disorders in humans (4).
Take-home and implications
This necessitates a reevaluation of what goes into our food, how it affects our gut microbiota and our health. Standard food safety tests include toxicity and carcinogenicity (ability to cause cancer), however, the importance not perturbing the natural flora of the intestine is becoming clear only now. These findings suggest the following in mice- intake of food/drink containing emulsifiers leads to weight gain and disorders such as diabetes, by directly increasing food intake. These findings need to be verified in humans.The intriguing realization that dawns on someone after looking at this study is that not just the quantity, but also the quality of the microorganisms in the mouse gut matters. In humans the importance of gut microbial diversity has been documented in other contexts (1-3, video below – courtesy MinuteEarth)
Limitations and Open Questions
Only 2 synthetic emulsifiers have been tested. We feel that this work makes a strong argument for the development of assay systems that monitor microbial health (especially gut microbes) for compounds added to food, medicines etc. Given that the findings have such strong implications, we hope to see in the future a wider spectrum of compounds (including the more natural products like lecithin) examined similarly by the authors and others.
The authors have only discussed in brief the possible mechanism underlying the change in the microbial population or how these changes result in increased inflammation. This remains a major open question.
Germ free mice already have a really bad situation in their gut, they are somewhat prone to inflammation. It is important to bear this in mind while interpreting the results of the fecal transplantation into germ free mice.
The study is a mouse study, it remains to be extended to humans.
An interview with Dr. Andrew Gewirtz
Q. From your work, it is clear that altered microbiota could lead to weight gain, fat deposition and the loss of the ability to control blood sugar levels, can this be reversed by altering the microbiota?
Our studies in mice indicate it is reversible but it takes some time.
Q. How do you think the emulsifiers are changing the gut microbiota? Can you elaborate on some potential mechanisms?
They seem to promote bacteria breaching the mucus, which promotes inflammation, which changes bacterial populations, possibly by favoring detrimental bacteria.
Q. Are you suggesting that the normal gut flora under different conditions (presence absence of emulsifiers) could turn pro-inflammatory? Are the other missing microbiota (in the presence of emulsifiers) keeping them in check under normal circumstances?
Q. What according to you are the major caveats of your study?
It is a mouse study.
Q. Did you face challenges in publishing this work, given that it has such strong implications?
Some reviewers suggested a dialog with food industry prior to publication but we argued our tax payer funded research did not require such approval. Nature editors agreed with us.
Q. Do you plan to take this study forward in humans? What would be a suitable cohort for such study?
Yes. Probably start with healthy college students.
Q. Your work clearly has implications for how we decide what to put in our foods.. What Changes would you suggest to the current process by which such compounds are screened, approved and used?
I think major overhaul is needed. Both more tests are needed and more information made readily available to consumers.
Q. Has your study affected your life and food choices?
Yes, my family has cut our consumption of processed foods in general and emulsifiers in particular.
1. “Structure, Function and Diversity of the Healthy Human Microbiome”,The Human Microbiome Project Consortium, Nature, 2012
2. “A metagenome-wide association study of gut microbiota in type 2 diabetes”, Junjie Qin et al., Nature, 2012
3. “A core gut microbiome in obese and lean twins”, Peter J. Turnbaugh et al., Nature, 2009
4. “Artificial sweeteners induce glucose intolerance by altering the gut microbiota”, Jotham Suez et al., Nature, 2014
5. “Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome”, Benoit Chassaing et al., Nature, 2015