@article{0e042cf9763343f1a5243853faa7c94b,
title = "Randomized Controlled-Feeding Study of Dietary Emulsifier Carboxymethylcellulose Reveals Detrimental Impacts on the Gut Microbiota and Metabolome",
abstract = "Background & Aims: Epidemiologic and murine studies suggest that dietary emulsifiers promote development of diseases associated with microbiota dysbiosis. Although the detrimental impact of these compounds on the intestinal microbiota and intestinal health have been demonstrated in animal and in vitro models, impact of these food additives in healthy humans remains poorly characterized. Methods: To examine this notion in humans, we performed a double-blind controlled-feeding study of the ubiquitous synthetic emulsifier carboxymethylcellulose (CMC) in which healthy adults consumed only emulsifier-free diets (n = 9) or an identical diet enriched with 15 g per day of CMC (n = 7) for 11 days. Results: Relative to control subjects, CMC consumption modestly increased postprandial abdominal discomfort and perturbed gut microbiota composition in a way that reduced its diversity. Moreover, CMC-fed subjects exhibited changes in the fecal metabolome, particularly reductions in short-chain fatty acids and free amino acids. Furthermore, we identified 2 subjects consuming CMC who exhibited increased microbiota encroachment into the normally sterile inner mucus layer, a central feature of gut inflammation, as well as stark alterations in microbiota composition. Conclusions: These results support the notion that the broad use of CMC in processed foods may be contributing to increased prevalence of an array of chronic inflammatory diseases by altering the gut microbiome and metabolome (ClinicalTrials.gov, number NCT03440229).",
keywords = "Emulsifier, Metabolism, Metabolome, Microbiota",
author = "Benoit Chassaing and Charlene Compher and Brittaney Bonhomme and Qing Liu and Yuan Tian and William Walters and Lisa Nessel and Clara Delaroque and Fuhua Hao and Victoria Gershuni and Lillian Chau and Josephine Ni and Meenakshi Bewtra and Lindsey Albenberg and Alexis Bretin and Liam McKeever and Ley, {Ruth E.} and Patterson, {Andrew D.} and Wu, {Gary D.} and Gewirtz, {Andrew T.} and Lewis, {James D.}",
note = "Funding Information: Funding This work was supported by National Institutes of Health grants DK115180, 5UL1TR001878, and P30-DK050306, and by the Max Planck Society. Benoit Chassaing{\textquoteright}s laboratory is supported by a Starting Grant from the European Research Council (ERC) under the European Union{\textquoteright}s Horizon 2020 research and innovation programme (grant agreement No. ERC-2018-StG- 804135), a Chaire d{\textquoteright}Excellence from IdEx Universit{\'e} de Paris (ANR-18-IDEX-0001), an Innovator Award from the Kenneth Rainin Foundation, a grant from the French Research Agency (Emulbiont, ANR-21-CE15–0042–01), and the national program “Microbiote” from INSERM. Andrew D. Patterson's laboratory is supported by the USDA National Institute of Food and Federal Appropriations under Project PEN04607 and Accession number 1009993. The funders had no role in the design of the study and data collection, analysis and interpretation, or in manuscript writing. Funding Information: The authors thank the Penn Center for Nutritional Science and Medicine and the Host-Microbial Analytic and Repository Core of the Center for Molecular Studies in Digestive and Liver Diseases (National Institutes of Health P30 DK050306). The authors thank Dr. Philip Smith from the Penn State Metabolomics Facility, and Nicholas Youngblut from the MPI. All authors had access to the study data and reviewed and approved the final manuscript. Order of Authors (with Contributor Roles):, Benoit Chassaing, PhD (Conceptualization: Supporting; Data curation: Supporting; Formal analysis: Supporting; Funding acquisition: Supporting; Investigation: Supporting; Methodology: Supporting; Writing ? original draft: Supporting), Charlene Compher, PhD (Conceptualization: Supporting; Formal analysis: Supporting; Investigation: Supporting; Project administration: Supporting; Writing ? original draft: Supporting), Brittaney Bonhomme, PhD (Conceptualization: Supporting; Data curation: Supporting; Formal analysis: Supporting; Writing ? original draft: Supporting), Qing Liu, PhD (Data curation: Supporting; Formal analysis: Supporting; Writing ? original draft: Supporting), Yuan Tian, PhD (Data curation: Supporting; Formal analysis: Supporting; Writing ? original draft: Supporting), William Walters, PhD (Data curation: Supporting; Formal analysis: Supporting; Writing ? original draft: Supporting), Lisa Nessel, PhD (Data curation: Supporting; Writing ? review & editing: Supporting), Clara Delaroque, PhD student (Data curation: Supporting; Formal analysis: Supporting), Fuhua Hao, PhD (Data curation: Supporting; Formal analysis: Supporting), Victoria Gershuni, PhD (Writing ? review & editing: Supporting), Lillian Chau, PhD (Data curation: Supporting; Writing ? review & editing: Supporting), Josephine Ni, PhD (Writing ? review & editing: Supporting), Meenakshi Bewtra, PhD (Writing ? review & editing: Supporting), Lindsey Albenberg, PhD (Writing ? review & editing: Supporting), Alexis Bretin, PhD (Data curation: Supporting; Writing ? original draft: Supporting), Liam McKeever, PhD (Conceptualization: Supporting; Data curation: Supporting; Writing ? review & editing: Supporting), Ruth Ley, PhD (Data curation: Supporting; Writing ? original draft: Supporting), Andrew Patterson, PhD (Conceptualization: Supporting; Data curation: Supporting; Formal analysis: Supporting; Funding acquisition: Supporting; Investigation: Supporting; Methodology: Supporting; Project administration: Supporting; Writing ? original draft: Supporting), Gary Wu, MD, PhD (Conceptualization: Supporting; Data curation: Supporting; Formal analysis: Supporting; Funding acquisition: Supporting; Investigation: Supporting; Methodology: Supporting; Project administration: Supporting; Supervision: Supporting; Writing ? original draft: Supporting), Andrew Gewirtz, PhD (Conceptualization: Supporting; Data curation: Supporting; Formal analysis: Supporting; Funding acquisition: Supporting; Investigation: Supporting; Methodology: Supporting; Project administration: Supporting; Resources: Supporting; Supervision: Supporting; Validation: Supporting; Writing ? original draft: Supporting), James Lewis, MD, PhD (Conceptualization: Supporting; Data curation: Supporting; Formal analysis: Supporting; Funding acquisition: Supporting; Investigation: Supporting; Methodology: Supporting; Project administration: Supporting; Resources: Supporting; Writing ? original draft: Supporting) Conflict of interest Dr Lewis consulted or served on an advisory board for Eli Lilly and Company, Samsung Bioepis, UCB, Bristol-Myers Squibb, Nestle Health Science, Merck, Celgene, Janssen Pharmaceuticals, Bridge Biotherapeutics, Entasis Therapeutics, AbbVie, Pfizer, Gilead, Arena Pharmaceuticals, Protagonist Therapeutics, Amgen, and Scipher Medicine. He has had research funding from Nestle Health Science, Takeda, Janssen Pharmaceuticals, and AbbVie. The remaining authors disclose no conflicts. Funding This work was supported by National Institutes of Health grants DK115180, 5UL1TR001878, and P30-DK050306, and by the Max Planck Society. Benoit Chassaing's laboratory is supported by a Starting Grant from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No. ERC-2018-StG- 804135), a Chaire d'Excellence from IdEx Universit? de Paris (ANR-18-IDEX-0001), an Innovator Award from the Kenneth Rainin Foundation, a grant from the French Research Agency (Emulbiont, ANR-21-CE15?0042?01), and the national program ?Microbiote? from INSERM. Andrew D. Patterson's laboratory is supported by the USDA National Institute of Food and Federal Appropriations under Project PEN04607 and Accession number 1009993. The funders had no role in the design of the study and data collection, analysis and interpretation, or in manuscript writing. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = mar,
doi = "10.1053/j.gastro.2021.11.006",
language = "English (US)",
volume = "162",
pages = "743--756",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "3",
}