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Background: Non-absorbed dietary emulsifiers, including carboxymethylcellulose (CMC), directly disturb intestinal microbiota, thereby promoting chronic intestinal inflammation in mice. A randomised controlled-feeding study (Functional Research on Emulsifiers in Humans, FRESH) found that CMC also detrimentally impacts intestinal microbiota in some, but not all, healthy individuals., Objectives: This study aimed to establish an approach for predicting an individual's sensitivity to dietary emulsifiers via their baseline microbiota., Design: We evaluated the ability of an in vitro microbiota model (MiniBioReactor Arrray, MBRA) to reproduce and predict an individual donor's sensitivity to emulsifiers. Metagenomes were analysed to identify signatures of emulsifier sensitivity., Results: Exposure of human microbiotas, maintained in the MBRA, to CMC recapitulated the differential CMC sensitivity previously observed in FRESH subjects. Furthermore, select FRESH control subjects (ie, not fed CMC) had microbiotas that were highly perturbed by CMC exposure in the MBRA model. CMC-induced microbiota perturbability was associated with a baseline metagenomic signature, suggesting the possibility of using one's metagenome to predict sensitivity to dietary emulsifiers. Transplant of human microbiotas that the MBRA model deemed CMC-sensitive, but not those deemed insensitive, into IL-10 -/- germfree mice resulted in overt colitis following CMC feeding., Conclusion: These results suggest that an individual's sensitivity to emulsifier is a consequence of, and can thus be predicted by, examining their baseline microbiota, paving the way to microbiota-based personalised nutrition., Competing Interests: Competing interests: LP-B received consulting and lecture fees as well as a grant from Takeda. None of the other authors declare competing interests., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)