TY - JOUR T1 - Systems genetics uncovers microbe-lipid-host connections in the murine gut JF - bioRxiv DO - 10.1101/2021.11.29.470403 SP - 2021.11.29.470403 AU - Q Zhang AU - V Linke AU - KA Overmyer AU - LL Traeger AU - K Kasahara AU - IJ Miller AU - DE Manson AU - TJ Polaske AU - RL Kerby AU - JH Kemis AU - EA Trujillo AU - TR Reddy AU - JD Russell AU - KL Schueler AU - DS Stapleton AU - ME Rabaglia AU - M Seldin AU - DM Gatti AU - GR Keele AU - DT Pham AU - JP Gerdt AU - EI Vivas AU - AJ Lusis AU - MP Keller AU - GA Churchill AU - HE Blackwell AU - KW Broman AU - AD Attie AU - JJ Coon AU - FE Rey Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/11/29/2021.11.29.470403.abstract N2 - The molecular bases of how host genetic variation impact gut microbiome remain largely unknown. Here, we used a genetically diverse mouse population and systems genetics strategies to identify interactions between molecular phenotypes, including microbial functions, intestinal transcripts and cecal lipids that influence microbe-host dynamics. Quantitative trait loci (QTL) analysis identified genomic regions associated with variations in bacterial taxa, bacterial functions, including motility, sporulation and lipopolysaccharide production, and levels of bacterial- and host-derived lipids. We found overlapping QTL for the abundance of Akkermansia muciniphila and cecal levels of ornithine lipids (OL). Follow-up studies revealed that A. muciniphila is a major source of these lipids in the gut, provided evidence that OL have immunomodulatory effects and identified intestinal transcripts co-regulated with these traits. Collectively, these results suggest that OL are key players in A. muciniphila-host interactions and support the role of host genetics as a determinant of responses to gut microbes.Competing Interest StatementThe authors have declared no competing interest. ER -