Beyond who is there: a post-translationallayer in the diet–microbiome relationship
Abstract: ** Lecture will be given in English**
The gut microbiome’s response to diet is usually read as achange in community composition — which organisms are present and which genesthey carry. Whether dietary substrate also reaches the microbial proteomepost-translationally is largely unexplored. Fermentation of soluble fiberyields acetate and acetyl-phosphate, the donors for bacterial lysineacetylation, giving a direct chemical route from diet to protein modification.
We fed mice soluble (pectin and inulin) or insoluble (cellulose)fiber for four weeks and enriched acetylated proteins from cecal and fecalcontents by anti-acetyllysine immunoprecipitation at the intact-protein level,analyzing both the captured fraction and its matched flow-through bydata-dependent mass spectrometry against a sample-matched, metagenome-derivedprotein database.
Soluble fiber raised cecal acetate and broadenedacetylated-protein capture roughly six-fold, with no overlap between dietgroups, more proteins captured rather than more of each, while matched bulkflow-through breadth was unchanged and pre-diet samples showed no asymmetry.The captured set was over-represented in fermentation and nitrogen-handlingenzymes. Glutamate dehydrogenase was retained in the cecal acetylated fractionwhile its bulk abundance there fell and both the gene and its carrier lineagesdeclined in the fecal metagenome, dissociating post-translational state fromabundance and gene dosage.
I will discuss what this designcan and cannot establish, including a direct cecal ammonia measurement thatbehaves as dilution rather than reduced production, and the recombinantenzymology needed to test whether this acetylation is regulatory.
