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 (Faecalibacterium prausnitzii), axenic clinical isolates of proinflammatory bacteria from CD patients (Proteus, Morganella, and Klebsiella 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 F. prausnitzii 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 Proteus and/or Veillonellaceae – 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.

KEYWORDS:

• Gut microbiota
• food additives
• inflammatory bowel disease
• Proteus
• Veillonella
• Faecalibacterium prausnitzii

Acknowledgments

We gratefully acknowledge the contributions of the entire clinical, hospital and laboratory staff affiliated with the ENIGMA project team.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data accession

The DNA sequencing data (fastq files) produced as part of this study are uploaded in NCBI SRA under accession number PRJNA779743.

Author Contributions

JJJ-L, LS, SK: study design, acquisition of data, analyses and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content; JJT, AdK, EN: acquisition of data, critical review and revision of the manuscript for important intellectual content. JZ, JH, AH, AW-O’B, GT, WL, JC, LO: study design, study organization (technical, ethics, and governance), resource and data provision, critical review and revision of the manuscript for important intellectual content; JJYS, JY: study design, supervision, project administration, critical review and revision of the manuscript for important intellectual content; SCN, MAK: study design, project administration and funding, critical review and revision of the manuscript for important intellectual content; MM study lead, project administration and funding, manuscript drafting, review and revision.

Additional information

Funding

The work presented in this manuscript was supported by The Leona M. and Harry B. Helmsley Charitable Trust. as part of the Eastern IBD Gut Microbiota (ENIGMA) project, and Croucher Senior Medical Research Fellowship. The research by J.J.J-L., L.S, J.J.T., S.K., A.dK., E.N., and M.M. was carried out at the Translational Research Institute, Woolloongabba, QLD 4102, Australia. The Translational Research Institute is supported by a grant from the Australian Government.