Repeated Oral Exposure to N ε-Carboxymethyllysine, a Maillard Reaction Product, Alleviates Gut Microbiota Dysbiosis in Colitic Mice

Abstract

Background: Diet is suggested to participate in the etiology of inflammatory bowel diseases (IBD). Repeated exposure to Maillard reaction products (MRPs), molecules resulting from reduction reactions between amino acids and sugars during food heating, has been reported to be either potentially detrimental or beneficial to health. Aims: The aim of this study is to determine the effect of repeated oral ingestion of Nε-carboxymethyllysine (CML), an advanced MRP, on the onset of two models of experimental IBD and on the gut microbiota composition of mice. Methods: Mice received either saline (control) or Nε-carboxymethyllysine daily for 21 days. For the last week of treatment, each group was split into subgroups, receiving dextran sulfate sodium salt (DSS) or trinitrobenzenesulfonic acid (TNBS) to induce colitis. Intensity of inflammation was quantified, and cecal microbiota characterized by bacterial 16S ribosomal RNA (rRNA) amplicon sequencing. Results: Daily oral administration of Nε-carboxymethyllysine did not induce intestinal inflammation and had limited impact on gut microbiota composition (Bacteroidaceae increase, Lachnospiraceae decrease). DSS and TNBS administration resulted in expected moderate experimental colitis with a shift of Bacteroidetes/Firmicutes ratio and a significant Proteobacteria increase but with distinct profiles: different Proteobacteria taxa for DSS, but mainly Enterobacteriaceae for TNBS. While Nε-carboxymethyllysine exposure failed to prevent the inflammatory response, it allowed maintenance of healthy gut microbiota profiles in mice treated with DSS (but not TNBS). Conclusions: Repeated oral exposure to CML limits dysbiosis in experimental colitis. IBD patients may modulate their microbiota profile by regulating the level and type of dietary MRP consumption.