Effect of food additives on key bacterial taxa and the mucosa-associated microbiota in Crohn’s disease. The ENIGMA study

Abstract

Food additives have been linked to the pro-inflammatory microbial dysbiosis associated with Crohn's disease (CD) but the underlying ecological dynamics are unknown. Here, we examine how selection of food additives affects the growth of multiple strains of a key beneficial bacterium (<i>Faecalibacterium prausnitzii</i>), axenic clinical isolates of proinflammatory bacteria from CD patients (<i>Proteus, Morganella</i>, and <i>Klebsiella</i> spp.), and the consortia of mucosa-associated microbiota recovered from multiple Crohn's disease patients. Bacterial growth of the axenic isolates was evaluated using a habitat-simulating medium supplemented with either sodium sulfite, aluminum silicate, carrageenan, carboxymethylcellulose, polysorbate 80, saccharin, sucralose, or aspartame, intended to approximate concentrations found in food. The microbial consortia recovered from post-operative CD patient mucosal biopsy samples were challenged with either carboxymethylcellulose and/or polysorbate 80, and the bacterial communities compared to unchallenged consortia by 16S rRNA gene amplicon profiling. Growth of all <i>F. prausnitzii</i> strains was arrested when either sodium sulfite or polysorbate 80 was added to cultures at baseline or mid-exponential phase of growth, and the inhibitory effects on the Gram-negative bacteria by sodium sulfite were conditional on oxygen availability. The effects from polysorbate 80, saccharin, carrageenan, and/or carboxymethylcellulose on these bacteria were strain-specific. In addition to their direct effects on bacterial growth, polysorbate 80 and/or carboxymethylcellulose can drive profound changes in the CD mucosa-associated microbiota via niche expansion of <i>Proteus</i> and/or <i>Veillonellaceae</i> - both implicated in early Crohn's disease recurrence. These studies on the interaction of food additives with the enteric microbiota provide a basis for dietary management in Crohn's disease.