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.
Highlights
The bloom of Proteobacteria is associated with many other diseases, and an increased abundance of Proteobacteria is suggested as a potential diagnostic marker of dysbiosis and the risk of disease [6]
The main aims of this project were to test the hypothesis that antimicrobial food additives can induce a compositional alteration, i.e., dysbiosis, of human gut microbiota and to find out whether host genotype plays any role in microbiota susceptibility to additives
To determine the effect of antimicrobial food additives on the composition of human gut microbiota, “humanised” gnotobiotic mice, i.e., originally germ-free mice colonised with human gut microbiota, were supplied from birth with either sterile water or water supplemented with a mixture of additives
Summary
Autoimmune, metabolic, neoplastic, and neurodegenerative diseases are associated with compositional and functional alterations of the gut microbiota, known as dysbiosis. The depletion of commensals leads to decreased microbiota diversity, which is associated with many immune-mediated and metabolic disorders [1]. A decrease in butyrate-producing Clostridiales is strongly correlated with the severity of inflammatory bowel disease (IBD) [2,3]. (2) The overgrowth of potentially pathogenic microbiota (pathobionts). In many immune-mediated diseases, the pathobionts outgrow other commensals. The bloom of Proteobacteria is associated with many other diseases, and an increased abundance of Proteobacteria is suggested as a potential diagnostic marker of dysbiosis and the risk of disease [6]
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