Human Intestinal Microbiome Determines Individualized Inflammatory Response to Dietary Emulsifier Carboxymethylcellulose Consumption
“I lurched away from the table after a few hours feeling like Elvis in Vegas – fat, drugged, and completely out of it.”
Studies continue to demonstrate that once perceived as harmless, the constituents of many ultra-processed foods can have a profoundly negative impact on human health. The increased consumption of ultra-processed foods parallels the increasing rise in chronic immune-mediated inflammatory diseases. A particularly egregious class of additives are the commonly used dietary emulsifiers such as carboxymethylcellulose (CMC).
CMC is also frequently used as a thickener and stabilizer. It can be found in a wide variety of common comestibles such as bread, cakes, and pastries; dairy products like ice cream, sauces, salad dressings, and gravies; beverages including certain types of fruit juices and flavored drinks; processed meats like sausages and lunch meats; gluten-free products in which it is used to mimic the structural properties of gluten in traditional baked goods; and convenience foods such as instant noodles, soups, and ready-to-eat meals.
CMC is not a natural product. It is produced from the waste products of cotton and wood manufacture, particularly from woodchips. However, because CMC is derived from cellulose, a plant fiber, current labeling laws allow manufacturers to count the inclusion of CMC as an “added fiber” on the label. Despite a lack of extensive safety testing, CMC was approved in the 1960s for use in foods based on the GRAS (generally regarded as safe) legislation originally developed in the 1950s.
Recent studies have shown that the mechanism involved in CMC-mediated chronic inflammation involves pro-inflammatory alteration of the gut microbiome. In other words, eating ultra-processed foods (UPFs) that contain CMC acts (at least via one pathway) by altering the bacteria in the gut to those that are associated with developing chronic inflammatory diseases like Crohn’s Disease, and ulcerative colitis. However, those same studies have also shown a very heterogeneous response among participants; not everyone is affected with equal risk and effect.
Utilizing the deleterious gut response of those individuals sensitive to CMC ingestion, as well as those who exhibited little change in their microbiome following CMC consumption, researchers were able to dig deeper into identifying what makes one person vulnerable and another immune to the effects of such additives as CMC.
- A study examining the differences between two participants from the FRESH study who were highly sensitive to CMC ingestion (CMS-sensitive, with significant detrimental gut microbiome alterations) and those who did not exhibit significant changes in gut flora or pathology following CMC consumption (CMC-insensitive).
- The study also utilized modeling by transplanting fecal microbiota samples into germ-free, colitis-prone mice. Germ-free mice have no natural gut microbiome of their own, but they readily serve as a host for transplanted gut bacteria, including that of humans. This allows the investigation of an individual’s gut microbiome in a way that is not feasible when working with human participants.
- There were no differences in genetic polymorphisms or basal intestinal gene expression between the groups (CMC-sensitive versus CMC-insensitive). In other words, there was no difference in the genes and their expression between those who developed an inflammatory response after consuming CMC and those who did not.
- This suggests that the vulnerability to CMC-induced inflammation lies in the form of some environmental impact.
- By using the transplanted germ-free mice model, it appeared that the basal microbiota influenced the impact of CMC on the risk of developing intestinal inflammation and subsequent chronic disease. In other words, the state of your baseline gut health prior to ingesting CMC determines your resilience to developing a full-blown inflammatory response in the gut, or colitis.
- This makes intuitive sense when we examine it in the context of an immune system response. A weakened immune system, whether from stress, fatigue, poor diet, or a chronic condition like type II diabetes, can make us more susceptible to certain viral infections. Having a “weakened” gut microbiome at the beginning makes us more susceptible to developing serious complications like colitis when we consume a diet rich in ultra-processed foods containing compounds like CMC.
- The study examined the gut microbiome of only two individuals who had a profoundly negative response to ingestion of CMC.
This current research adds to the knowledge base in understanding the human ecosystem. The individual dietary response is the result of a complex interaction between an individual’s baseline genetics (what we are born with), epigenetic expression (the environmental impact of turning our genes on and off), human physiology, and our gut microbiome. This study suggests a powerful role for the gut microbiome in determining the extent of an individual’s vulnerability to dietary-induced pathologies like CMC-associated inflammatory bowel disruption. It provides another thread in the weft and the warp, powerfully linking the human gut microbiome and the immune system.
This study suggests a potential pathway for diseases previously considered autoimmune, like Crohn’s disease, that originate with the health of our gut bacteria. Currently, there is evidence and ongoing investigation suggesting that the origin of Parkinson’s disease, long considered strictly a degenerative neurological disease confined to the brain, also may originate in the gut. Like the ongoing research regarding Parkinson’s disease, much more evidence is needed to establish a causal relationship.
However, given that the composition of our individual gut microbiome can be significantly affected – for better or worse – by our conscious dietary choices, this study adds to a growing body of evidence detailing the importance of what we choose to eat. This knowledge empowers us as individuals to be proactive in determining our own health and wellness or risk developing disability and disease.
Daniel, N., Wu, G. D., Walters, W., Lewis, J., Gewitz, A. T., & Chassaing, B. (2023). Human Intestinal Microbiome Determines Individualized Inflammatory Response to Dietary Emulsifier Carboxymethylcellulose Consumption. CMGH, DOI:https://doi.org/10.1016/j.jcmgh.2023.11.001.
Chassaing B, Compher C, Bonhomme B, Liu Q, Tian Y, Walters W, Nessel L, Delaroque C, Hao F, Gershuni V, Chau L, Ni J, Bewtra M, Albenberg L, Bretin A, McKeever L, Ley RE, Patterson AD, Wu GD, Gewirtz AT, Lewis JD. Randomized Controlled-Feeding Study of Dietary Emulsifier Carboxymethylcellulose Reveals Detrimental Impacts on the Gut Microbiota and Metabolome. Gastroenterology. 2022 Mar;162(3):743-756. doi: 10.1053/j.gastro.2021.11.006
Lane MM, Davis JA, Beattie S, et al. Ultraprocessed food and chronic noncommunicable diseases: A systematic review and meta-analysis of 43 observational studies. Obesity Reviews. 2021; 22:e13146. https://doi.org/10.1111/obr.13146
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 (Chassaing, et al., 2021)