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Inflammatory responses to the food additive carboxymethylcellulose (CMC) may depend on the unique characteristics of an individual’s microbiome, according to recent research.
These findings suggest that CMC, which is commonly used as a thickener and emulsifier to improve texture and shelf life of food, could potentially trigger chronic inflammation in genetically prone individuals, although more work is needed to pinpoint the exact microbiota involved, reported lead author Noëmie Daniel, PhD, of the French National Institute of Health and Medical Research (INSERM), Paris, and colleagues.“Preclinical work has shown that [CMC] consumption detrimentally impacts the intestinal microbiota in a way that promotes chronic inflammation,” the investigators wrote in a research letter in Cellular and Molecular Gastroenterology and Hepatology.
They published the results of a randomized, double-blind controlled trial that showed that the seven individuals exposed to a CMC-supplemented diet had “significant alterations in microbiota composition and metabolome” compared with the nine control subjects.
Yet responses to CMC varied widely. In the treatment group, some participants were relatively insensitive to CMC, while two participants had “stark alterations” in their microbiome.
“Such CMC sensitivity was not associated with overt signs of intestinal inflammation but nonetheless might mark proneness to chronic inflammation, compelling us to better understand mechanisms that mediate CMC sensitivity,” the investigators wrote.
To learn more, Dr. Daniel and colleagues conducted the present study, which involved a series of analyses and experiments.
They first compared inflammatory bowel disease-associated mutations and basal gene expression between CMC-sensitive and CMC-insensitive individuals from their previous trial. Neither were associated with CMC sensitivity, they found.
Evaluating microbiota was a more fruitful approach. Microbiome multivariable association with linear models analysis revealed 11 amplicon sequence variants (ASVs) that differed between groups.
“This algorithm did not detect differences between randomly selected subjects, arguing that ASVs that are associated with CMC sensitivity were not false discoveries but rather had marked, and perhaps contributed to, CMC sensitivity status,” the investigators wrote.
Next, they transplanted pre-CMC fecal samples from 2 CMC-sensitive and 2 CMC-insensitive individuals into germ-free, colitis-prone, interleukin 10-/- mice. Exposing these mice to CMC led to distinct changes in microbiota that was not clearly associated with the sensitivity status of the donor. However, mice that received transplants from CMC-sensitive individuals demonstrated increased microbiota-derived proinflammatory markers, increased microbiota encroachment, and “stark” intestinal inflammation after CMC consumption, suggesting that these responses were somehow mediated by the microbiome.
“These [results] indicate a role for basal microbiotas in influencing CMC impact on this cardinal feature of intestinal inflammation and suspected driver of chronic diseases,” the investigators wrote.
“Our findings suggest that the microbiota participate in the extent to which an individual harbors proneness to CMC-induced inflammatory diseases,” they added. “Accordingly, CMC consumption may be one trigger of chronic inflammation in genetically prone individuals colonized with a given microbial ecosystem.”
Research on a larger number of participants appears needed to substantiate their observations and determine the exact microbiota contributor(s) driving CMC sensitivity, the researchers concluded.
The investigators disclosed no conflicts of interest. Funding support came from a starting grant from the European Research Council under the European Union’s Horizon 2020 research and innovation program, a Chaire d’Excellence from IdEx Université de Paris, an award from the Fondation de l’Avenir, ANR grants EMULBIONT and DREAM, and the national program Microbiote from INSERM (B.C.). Supported also came from National Institutes of Health grants, the Penn Center for Nutritional Science and Medicine, and the Max Planck Society.
The consumption of highly processed foods, enriched with food additives, is associated with an increased risk of developing inflammatory bowel disease (IBD). Alteration of the intestinal barrier and microbiota encroachment on epithelial cells is thought to be one of the mechanisms leading to inappropriate mucosal immune activation in response to food additive intake. However, we still do not know why some exposed individuals develop IBD while others do not. The findings of Daniel and colleagues suggest that proinflammatory sensitivity to the food additive carboxymethylcellulose (CMC) is primarily dependent on the composition of the gut microbiota, and that this sensitivity can be, at least partially, transferable, using fecal microbiota transfers in a mouse model of IBD. In particular, they identified 11 taxa of the host basal microbiota associated with the development of intestinal inflammation in response to CMC.
Finally, this study also illustrates the relevance of systematically assessing the impact of food additives and emulsifiers on the gut microbiota and intestinal physiology in order to evaluate their safety using translational approaches similar to those applied by Daniel and colleagues.
Nicolas Benech, MD, PhD is an assistant professor at the Lyon 1 University and Gastroenterology department, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France, the director of the Lyon Fecal Microbiota transplantation Center, and cofounder of the Lyon GEM Microbiota Study Group. He has no conflicts.
The consumption of highly processed foods, enriched with food additives, is associated with an increased risk of developing inflammatory bowel disease (IBD). Alteration of the intestinal barrier and microbiota encroachment on epithelial cells is thought to be one of the mechanisms leading to inappropriate mucosal immune activation in response to food additive intake. However, we still do not know why some exposed individuals develop IBD while others do not. The findings of Daniel and colleagues suggest that proinflammatory sensitivity to the food additive carboxymethylcellulose (CMC) is primarily dependent on the composition of the gut microbiota, and that this sensitivity can be, at least partially, transferable, using fecal microbiota transfers in a mouse model of IBD. In particular, they identified 11 taxa of the host basal microbiota associated with the development of intestinal inflammation in response to CMC.
Finally, this study also illustrates the relevance of systematically assessing the impact of food additives and emulsifiers on the gut microbiota and intestinal physiology in order to evaluate their safety using translational approaches similar to those applied by Daniel and colleagues.
Nicolas Benech, MD, PhD is an assistant professor at the Lyon 1 University and Gastroenterology department, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France, the director of the Lyon Fecal Microbiota transplantation Center, and cofounder of the Lyon GEM Microbiota Study Group. He has no conflicts.
The consumption of highly processed foods, enriched with food additives, is associated with an increased risk of developing inflammatory bowel disease (IBD). Alteration of the intestinal barrier and microbiota encroachment on epithelial cells is thought to be one of the mechanisms leading to inappropriate mucosal immune activation in response to food additive intake. However, we still do not know why some exposed individuals develop IBD while others do not. The findings of Daniel and colleagues suggest that proinflammatory sensitivity to the food additive carboxymethylcellulose (CMC) is primarily dependent on the composition of the gut microbiota, and that this sensitivity can be, at least partially, transferable, using fecal microbiota transfers in a mouse model of IBD. In particular, they identified 11 taxa of the host basal microbiota associated with the development of intestinal inflammation in response to CMC.
Finally, this study also illustrates the relevance of systematically assessing the impact of food additives and emulsifiers on the gut microbiota and intestinal physiology in order to evaluate their safety using translational approaches similar to those applied by Daniel and colleagues.
Nicolas Benech, MD, PhD is an assistant professor at the Lyon 1 University and Gastroenterology department, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France, the director of the Lyon Fecal Microbiota transplantation Center, and cofounder of the Lyon GEM Microbiota Study Group. He has no conflicts.
Inflammatory responses to the food additive carboxymethylcellulose (CMC) may depend on the unique characteristics of an individual’s microbiome, according to recent research.
These findings suggest that CMC, which is commonly used as a thickener and emulsifier to improve texture and shelf life of food, could potentially trigger chronic inflammation in genetically prone individuals, although more work is needed to pinpoint the exact microbiota involved, reported lead author Noëmie Daniel, PhD, of the French National Institute of Health and Medical Research (INSERM), Paris, and colleagues.“Preclinical work has shown that [CMC] consumption detrimentally impacts the intestinal microbiota in a way that promotes chronic inflammation,” the investigators wrote in a research letter in Cellular and Molecular Gastroenterology and Hepatology.
They published the results of a randomized, double-blind controlled trial that showed that the seven individuals exposed to a CMC-supplemented diet had “significant alterations in microbiota composition and metabolome” compared with the nine control subjects.
Yet responses to CMC varied widely. In the treatment group, some participants were relatively insensitive to CMC, while two participants had “stark alterations” in their microbiome.
“Such CMC sensitivity was not associated with overt signs of intestinal inflammation but nonetheless might mark proneness to chronic inflammation, compelling us to better understand mechanisms that mediate CMC sensitivity,” the investigators wrote.
To learn more, Dr. Daniel and colleagues conducted the present study, which involved a series of analyses and experiments.
They first compared inflammatory bowel disease-associated mutations and basal gene expression between CMC-sensitive and CMC-insensitive individuals from their previous trial. Neither were associated with CMC sensitivity, they found.
Evaluating microbiota was a more fruitful approach. Microbiome multivariable association with linear models analysis revealed 11 amplicon sequence variants (ASVs) that differed between groups.
“This algorithm did not detect differences between randomly selected subjects, arguing that ASVs that are associated with CMC sensitivity were not false discoveries but rather had marked, and perhaps contributed to, CMC sensitivity status,” the investigators wrote.
Next, they transplanted pre-CMC fecal samples from 2 CMC-sensitive and 2 CMC-insensitive individuals into germ-free, colitis-prone, interleukin 10-/- mice. Exposing these mice to CMC led to distinct changes in microbiota that was not clearly associated with the sensitivity status of the donor. However, mice that received transplants from CMC-sensitive individuals demonstrated increased microbiota-derived proinflammatory markers, increased microbiota encroachment, and “stark” intestinal inflammation after CMC consumption, suggesting that these responses were somehow mediated by the microbiome.
“These [results] indicate a role for basal microbiotas in influencing CMC impact on this cardinal feature of intestinal inflammation and suspected driver of chronic diseases,” the investigators wrote.
“Our findings suggest that the microbiota participate in the extent to which an individual harbors proneness to CMC-induced inflammatory diseases,” they added. “Accordingly, CMC consumption may be one trigger of chronic inflammation in genetically prone individuals colonized with a given microbial ecosystem.”
Research on a larger number of participants appears needed to substantiate their observations and determine the exact microbiota contributor(s) driving CMC sensitivity, the researchers concluded.
The investigators disclosed no conflicts of interest. Funding support came from a starting grant from the European Research Council under the European Union’s Horizon 2020 research and innovation program, a Chaire d’Excellence from IdEx Université de Paris, an award from the Fondation de l’Avenir, ANR grants EMULBIONT and DREAM, and the national program Microbiote from INSERM (B.C.). Supported also came from National Institutes of Health grants, the Penn Center for Nutritional Science and Medicine, and the Max Planck Society.
Inflammatory responses to the food additive carboxymethylcellulose (CMC) may depend on the unique characteristics of an individual’s microbiome, according to recent research.
These findings suggest that CMC, which is commonly used as a thickener and emulsifier to improve texture and shelf life of food, could potentially trigger chronic inflammation in genetically prone individuals, although more work is needed to pinpoint the exact microbiota involved, reported lead author Noëmie Daniel, PhD, of the French National Institute of Health and Medical Research (INSERM), Paris, and colleagues.“Preclinical work has shown that [CMC] consumption detrimentally impacts the intestinal microbiota in a way that promotes chronic inflammation,” the investigators wrote in a research letter in Cellular and Molecular Gastroenterology and Hepatology.
They published the results of a randomized, double-blind controlled trial that showed that the seven individuals exposed to a CMC-supplemented diet had “significant alterations in microbiota composition and metabolome” compared with the nine control subjects.
Yet responses to CMC varied widely. In the treatment group, some participants were relatively insensitive to CMC, while two participants had “stark alterations” in their microbiome.
“Such CMC sensitivity was not associated with overt signs of intestinal inflammation but nonetheless might mark proneness to chronic inflammation, compelling us to better understand mechanisms that mediate CMC sensitivity,” the investigators wrote.
To learn more, Dr. Daniel and colleagues conducted the present study, which involved a series of analyses and experiments.
They first compared inflammatory bowel disease-associated mutations and basal gene expression between CMC-sensitive and CMC-insensitive individuals from their previous trial. Neither were associated with CMC sensitivity, they found.
Evaluating microbiota was a more fruitful approach. Microbiome multivariable association with linear models analysis revealed 11 amplicon sequence variants (ASVs) that differed between groups.
“This algorithm did not detect differences between randomly selected subjects, arguing that ASVs that are associated with CMC sensitivity were not false discoveries but rather had marked, and perhaps contributed to, CMC sensitivity status,” the investigators wrote.
Next, they transplanted pre-CMC fecal samples from 2 CMC-sensitive and 2 CMC-insensitive individuals into germ-free, colitis-prone, interleukin 10-/- mice. Exposing these mice to CMC led to distinct changes in microbiota that was not clearly associated with the sensitivity status of the donor. However, mice that received transplants from CMC-sensitive individuals demonstrated increased microbiota-derived proinflammatory markers, increased microbiota encroachment, and “stark” intestinal inflammation after CMC consumption, suggesting that these responses were somehow mediated by the microbiome.
“These [results] indicate a role for basal microbiotas in influencing CMC impact on this cardinal feature of intestinal inflammation and suspected driver of chronic diseases,” the investigators wrote.
“Our findings suggest that the microbiota participate in the extent to which an individual harbors proneness to CMC-induced inflammatory diseases,” they added. “Accordingly, CMC consumption may be one trigger of chronic inflammation in genetically prone individuals colonized with a given microbial ecosystem.”
Research on a larger number of participants appears needed to substantiate their observations and determine the exact microbiota contributor(s) driving CMC sensitivity, the researchers concluded.
The investigators disclosed no conflicts of interest. Funding support came from a starting grant from the European Research Council under the European Union’s Horizon 2020 research and innovation program, a Chaire d’Excellence from IdEx Université de Paris, an award from the Fondation de l’Avenir, ANR grants EMULBIONT and DREAM, and the national program Microbiote from INSERM (B.C.). Supported also came from National Institutes of Health grants, the Penn Center for Nutritional Science and Medicine, and the Max Planck Society.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY