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.

Microbiota Therapy in Inflammatory Bowel Disease

“…Besides producing short-chain fatty acids the genus Ruminococcus degrades mucus. Alterations that were consistently found in several other studies in CD patients include a relative reduction of Faecalibacterium prausnitzii and of Roseburia hominis as well [30‒40].…”

Carrageenan in the Diet: Friend or Foe for Inflammatory Bowel Disease?

“…and Veillonellaceae which have been associated with promoting the recurrence of CD. Moreover, polysorbate 80 and sodium sulphite have an inhibitory effect on the growth of Faecalibacterium prausnitzii , which appears to have a favorable effect on CD [ 46 ]. Glycerol monolaurate caused intestinal dysbiosis in mice, reduced the content of anti-inflammatory bacteria such as Akkermansia and increased levels of LPS [ 47 ].…”

Use of oral diet and nutrition support in management of stricturing and fistulizing Crohn's disease

“…12 Additionally, certain food additives have been associated with CD; however, there is a paucity of data focusing on stricturing and fistulizing disease. [13][14][15][16] Given diet's role in development of IBD, various diets have also been investigated as treatments for CD. Multiple studies have evaluated various exclusion diets in treatment of CD, such as the specific carbohydrate diet (SCD) and the Crohn's Disease Exclusion Diet (CDED).…”

“…In CD, a diet pattern with low fruit and vegetable intake and high intake of processed foods (snacks, prepared meals, nonalcoholic beverages, sauces) was associated with increased risk, although data are limited for diet patterns associated with stricturing and fistulizing disease 12 . Additionally, certain food additives have been associated with CD; however, there is a paucity of data focusing on stricturing and fistulizing disease 13–16 . Given diet's role in development of IBD, various diets have also been investigated as treatments for CD.…”