Anaerobutyricum hallii promotes the functional depletion of a food carcinogen in diverse healthy fecal microbiota

Abstract

Introduction Anaerobutyricum hallii is a human gut commensal that transforms the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), a carcinogen from cooked meat. The transformation mechanism involves the microbial production of acrolein from glycerol, and its conjugation with PhIP, thus blocking its mutagenic potential. A potential cancer prevention strategy could therefore involve supplementing complex human microbial communities with metabolically competent bacteria such as A. hallii that can deplete PhIP. However, it has not been established how the proportion of A. hallii in diverse healthy human gut microbial communities relates to functional capacity for PhIP transformation and, moreover, how supplementing microbiomes with A. hallii affects this function. Methods In this study, shotgun metagenomics was used to study taxonomic profiling, the abundance of glycerol/diol dehydratase ( gdh )-harboring taxa, the proportion of resident A. hallii , and the reconstruction of A. hallii population genomes in the fecal samples of 20 healthy young adult donors. Furthermore, the influence of supplementing 10 6 cells/mL of A. hallii DSM 3353 with diluted fecal microbiota was characterized. Results and discussion Six microbiota were assigned to Bacteroides , nine to Prevotella , and five to Ruminococcus by enterotype-associated clustering. The total number of gdh copies in the 20 fecal microbiota expressed per 10 10 bacterial cells ranged between 1.32 × 10 8 and 1.15 × 10 9 . Eighteen out of the 20 donors were dominated by A. hallii , representing between 33% and 94% of the total gdh relative abundance of the samples. The microbiota with low A. hallii abundance (i.e., with a relative abundance < 1%) transformed less PhIP than the microbiota with high A. hallii abundance (i.e., with a relative abundance > 1%). Furthermore, supplementing the low- A. hallii -abundant microbiota with glycerol significantly increased the PhIP transformation capacity after 6 h while reducing total short-chain fatty acid (SCFA) levels, which is most likely due to acrolein production. Although acetate decreased in all microbiota with glycerol and with the combination of glycerol and A. hallii , for most of the microbiomes, butyrate production increased over time. Thus, for a significant number of diverse healthy human fecal microbiomes, and especially when they have little of the taxa to start with, supplementing A. hallii increases PhIP transformation. These findings suggest the need to test in vivo whether supplementing microbiomes with A. hallii reduces PhIP exposure.