Intestinal epithelial transcription factor HNF4A protects against microbiota-dependent spontaneous colitis associated with expansion of Akkermansia muciniphila. Akkermansia muciniphila

We sequenced the genomes of four A. muciniphila strains isolated from healthy mice or mouse models of colitis. MmAkk1 was isolated from a healthy 6-week old female C57BL/6J mouse. This mouse was ordered from Jackson Laboratories (Bar Harbor, ME), and was being maintained on PicoLab Rodent Diet 20 (5053) in a non-specific pathogen free (SPF) Duke University facility at the time of sampling. MmAkk2 was isolated from a 5-week old female Muc2-/- mouse (PMID: 11872843). MmAkk3 was isolated from a 48 week old male Hnf4adIEC (generated using the Hnf4afl/+ (Jackson Laboratories Stock no. 004665) and Vil1:Cre+ mice (Jackson Laboratories Stock no. 004586), and initially characterized in PMID: 18338782 and 19389805). Both Muc2-/- and Hnf4adIEC mice were bred in-house at two separate SPF Duke facilities and fed PicoLab Mouse Diet 20 (5053). MmAkkUCB1 was isolated from a healthy C57BL/6J mouse fed Envigo Teklad Global diet 2018, and housed under SPF conditions at University of California at Berkeley. Pangenomic comparison of these strains to other previously published mouse strains and reference strains belonging to known Akkermansia phylogroups revealed that MmAkk2 and MmAkk3, along with another published strain (Biosample Accession: SAMEA104102608) clustered separately from other phylogroups into a new phylogroup we named AmV. Based on Anvi'o functional enrichment analysis and KEGG pathway completeness analysis we uncovered potential functions and pathways linked to gene clusters enriched and depleted in AmV compared to other phylogroups. Overall these results provide context for how our newly sequenced strains compare to other known mouse A. muciniphila strains, reveal a new phylogroup of A. muciniphila containing two isolates from mouse models of colitis, and provides initial functional characterization of this phylogroup compared to existing phylogroups.