Food Preservatives Induce Proteobacteria Dysbiosis in Human-Microbiota Associated Nod2-Deficient Mice

Abstract

The worldwide incidence of many immune-mediated and metabolic diseases, initially affecting only the wealthy Western countries, is increasing rapidly. Many of these diseases are associated with the compositional and functional alterations of gut microbiota, i.e., dysbiosis. The most consistent markers of the dysbiosis are a decrease in microbiota diversity and an expansion of Proteobacteria. The role of food preservatives as potential triggers of gut microbiota dysbiosis has been long overlooked. Using a human microbiota-associated mouse model, we demonstrate that a mixture of common antimicrobial food additives induces dysbiosis characterised by an overgrowth of Proteobacteria phylum and a decrease in the Clostridiales order. Remarkably, human gut microbiota in a Nod2-deficient genetic background is even more susceptible to the induction of Proteobacteria dysbiosis by additives than the microbiota in a wild-type background. To conclude, our data demonstrate that antimicrobial food additives trigger gut microbiota dysbiosis in both wild-type and Nod2-deficient backgrounds and at the exposure levels reached in European populations. Whether this additive-modified gut microbiota plays a significant role in the pathogenesis of immune-mediated and metabolic diseases remains to be elucidated.

Gut Microbiota and NAFLD: Pathogenetic Mechanisms, Microbiota Signatures, and Therapeutic Interventions

“…The effect of food additives on gut microbiota has been long overlooked, but recently, several groups, including ours published data demonstrating that some human gut microbes are highly susceptible to food preservatives [ 18 ] and that the exposure to common preservatives promotes Proteobacteria overgrowth [ 19 ]. Chassaing et al found that dietary emulsifiers directly alter human gut microbiota composition, and that the emulsifier-modified microbiota can induce intestinal inflammation when transplanted to germ-free mice [ 20 ].…”

The Multifaceted Roles of Diet, Microbes, and Metabolites in Cancer

“…There are few studies looking at the effects of food preservatives on the microbiota, typically limited to using animal models [ 67 ]. A recent study showed that a combination of antimicrobial food preservatives (sodium benzoate, sodium nitrite, and potassium sorbate) induced a decrease in the abundance of Firmicutes ( Clostridiales order) while increasing Proteobacteria ( Burkholderiales order) in human-microbiota associated mice, suggesting a possible link to dysbiosis [ 68 ]. A recent literature review illustrated evidence suggesting that food additives can drive dysbiosis through the reduction of anti-inflammatory bacteria such as Clostridium tyrobutyricum and Lactobacillus paracasei with a link to irritable bowel syndrome [ 69 ].…”

The impact of selected food additives on the gastrointestinal tract in the example of nonspecific inflammatory bowel diseases

“…In addition, the authors found a strong relationship between the NOD2 gene mutation and intestinal microflora disorders after administration of preservatives, compared to the group without such a mutation. The researchers also point out the need to study the effect of each of the above food additives on the intestinal microbiome separately [81]. Hrncirova et al also investigated the sensitivity of some bacteria in the human intestinal microflora to preservatives.…”