An answer here requires two provisos. One, inflammation being an essential feature of normal immune system function, that it per se is not the problem so much as its inappropriate start, control or stop. In other words, a healthy body is one that properly modulates inflammation. For the purpose of this question then the issue is inappropriate inflammation that entails persistent GI tract disturbance and barrier function disruption, and is implicated in Metabolic syndrome that some say is more accurately ‘chronic systemic low-grade inflammation induced energy reallocation‘ (1).
Two, effect of diet on physiology in general and on immune function in particular is much more difficult to dissect than other areas of medicine. An article in Vox recently explained why this is so (2). Summarizing from this piece,
- It’s not practical to run randomized trials for most big nutrition questions
- So nutrition researchers have to rely on observational studies, which are rife with uncertainty.
- Many nutrition studies rely on (wildly imprecise) food surveys.
- People and food are diverse.
- Conflict of interest is a huge problem in nutrition research.
So if a food ingredient causes inappropriate inflammation, studies ranging from lab-based to animal models as well as those in humans should show this. An example of such a food ingredient is found among dietary emulsifiers, a group of processed food ingredients that a body of data suggest play a role in sculpting gut microbiota away from commensal towards the more pathogenic kind. Gist of these studies is that such a shift tends to be accompanied by gut wall thinning, and greater likelihood of barrier function disruption and leakage of microbial antigens into systemic circulation.
Dietary emulsifiers are ubiquitous food additives in modern processed food. They fall under the so-called GRAS (generally recognized as safe) loophole in the 1958 law that the US Congress passed. The loophole consists of an exemption to bypass the FDA’s safety review process for ingredients GRAS. As such, companies prove on their own that GRAS are indeed GRAS. A recent Center for Public Integrity report notes that in the years since, the number of such food additives falling under GRAS ‘has skyrocketed from 800 to >10000‘ (3).
Emulsifiers (Emulsion) are molecules with both hydro- and lipophilic portions. This helps them maintain fat molecules in aqueous suspensions or water-soluble ones in a hydrophobic environment. In processed food and beverages, they’re used to extend product stability and slow the phase separation rate. According to Glade et al, dietary emulsifiers ‘maintain the texture, hydration, plasticity, fluidity, consistency, viscosity, volume, structural integrity, color, heat resistance, mold resistance, mouthfeel and taste of multiphase processed food and beverages, and tend to be considered harmless‘ (4).
Carboxymethylcellulose, a commonly used dietary emulsifier
One of the most commonly used dietary emulsifiers is the artificial Carboxymethyl cellulose. Water soluble, used as a thickener, emulsion stabilizer and suspending agent, it’s found in everything from dry pet foods, frozen dairy foods, diet sodas, white and sparkling wines, tortillas (4).
In vitro tests showed that carboxymethylcellulose can penetrate GI tract mucus more readily because it hydrates more easily compared to other non-starch polysaccharides (5, 6). OTOH, it doesn’t ferment or bind to cholesterol or bile acids meaning it doesn’t benefit the GI tract either. So what does it do? One study showed it exacerbated the growth of Neisseria gonorrhoeae, a pathogenic bacterium (7). In other words, at least one in vitro study showed carboxymethylcellulose has the capacity to support pathogen metabolism by increasing the availability of free sugars within the GI tract mucus layer.
Mouse Model Studies Of Carboxymethylcellulose Show It Can Promote/Support Inappropriate Inflammation
In a mouse model study (8), mice were fed carboxymethylcellulose (2%). Such mice had extensive bacterial overgrowth in their small intestine and mucosal inflammation, suggesting its sustained intake had severely perturbed their GI tract ecology and local pH, helping alter the relative proportions of commensal and pathogenic GI tract microbes.
In another study, mice fed carboxymethylcellulose dissolved in water (~1%w/v when they’re found in various foods at up to 2%) were compared to those fed water alone (9). The former developed a range of colonic inflammation that ranged all the way from low-grade to symptomatic colitis. Substantial thinning of colonic mucus layer inevitable outcome of such inflammation, bacterial antigens could more easily penetrate intestine contributing to systemic inflammation. Again extensive bacterial overgrowth occurred, including species such as mucolytic Ruminococcus gnavus and inflammatory Proteobacteria, i.e., not the beneficial kind.
Human Studies Of Carboxymethylcellulose Show It Can Modulate Dietary Absorption and Promote Fecal Incontinence
When taken as a substitute for dietary fiber, carboxymethylcellulose inhibits absorption of dietary flavonoids (10). The hypothesis is carboxymethylcellulose deprives gut microbes of the fermentable energy they need to enzymatically convert dietary flavonoids to their more absorbable counterparts. Flavonoids are common dietary components of fruits, vegetables, tea and wine and their intake is inversely linked to chronic cardiovascular diseases.
In a randomized, placebo-controlled trial of 206 subjects, carboxymethylcellulose increased fecal incontinence frequency when taken at 16 grams daily (11).
Thus far, in vitro and mouse model studies show a clearer propensity of carboxymethycellulose to promote inappropriate intestinal inflammation while the data from human studies, though less comprehensive, also hint at the same. As Chassaing et al point out (9), their GRAS status means that these kinds of food additives haven’t been carefully tested, and even such tests as have been done were intended to detect acute toxicity or tumor-inducing propensity. Such studies don’t study the effect of chronic, lower dose exposure that mimics regular dietary exposure, an important gap in food science and safety research.
1. Ruiz-Núñez, Begoña, et al. “Lifestyle and nutritional imbalances associated with Western diseases: causes and consequences of chronic systemic low-grade inflammation in an evolutionary context.” The Journal of nutritional biochemistry 24.7 (2013): 1183-1201.
2. I asked 8 researchers why the science of nutrition is so messy. Here’s what they said. Julia Belluz, Vox, Jan 16, 2016. Why (almost) everything you know about food is wrong
3. Why the FDA doesn’t really know what’s in your food. Erin Quinn, Chris Young, Center for Public Integrity, April 14, 2015. Why the FDA doesn’t really know what’s in your food
4. Glade, Michael J., and Michael M. Meguid. “Dietary Emulsifiers, The Human Intestinal Mucus and Microbiome, and Dietary Fiber.” Nutrition (2015).
5. Adiotomre, Joseph, et al. “Dietary fiber: in vitro methods that anticipate nutrition and metabolic activity in humans.” The American journal of clinical nutrition 52.1 (1990): 128-134.
6. Bliss, Donna Z., et al. “In vitro degradation and fermentation of three dietary fiber sources by human colonic bacteria.” Journal of agricultural and food chemistry 61.19 (2013): 4614-4621. http://naldc.nal.usda.gov/downlo…
7. Arko, R. J., et al. “Effects of tampon components on growth and dissemination of Neisseria gonorrhoeae.” The British journal of venereal diseases 58.2 (1982): 105-108. http://www.ncbi.nlm.nih.gov/pmc/…
8. Swidsinski, Alexander, et al. “Bacterial overgrowth and inflammation of small intestine after carboxymethylcellulose ingestion in genetically susceptible mice.” Inflammatory bowel diseases 15.3 (2009): 359-364. http://www.charite.de/arbmkl/pub…
9. Chassaing, Benoit, et al. “Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome.” Nature 519.7541 (2015): 92-96. http://bms.ucsf.edu/sites/ucsf-b…
10. Shimoi, Kayoko, et al. “Intestinal absorption of luteolin and luteolin 7‐O‐β‐glucoside in rats and humans.” FEBS letters 438.3 (1998): 220-224. http://onlinelibrary.wiley.com/d…
11. Bliss, Donna Z., et al. “Dietary fiber supplementation for fecal incontinence: a randomized clinical trial.” Research in nursing & health 37.5 (2014): 367-378. http://www.ncbi.nlm.nih.gov/pmc/…