Dietary S. maltophilia induces supersized lipid droplets by enhancing lipogenesis and ER-LD contacts in C. elegans

Dietary and symbiotic bacteria can exert powerful influence on metazoan lipid metabolism. Recent studies have emerged that microbiota have a role in animal obesity and related health disorders, but the mechanisms by which bacteria influence lipid storage in their host are unknown. To reduce the complexity of the relationship between gut microbiota and the host, Caenorhabditis elegans (C. elegans) has been chosen as a model organism to study interspecies interaction. Here, we demonstrate that feeding C. elegans with an opportunistic pathogenic bacterium Stenotrophomonas maltophilia (S. maltophilia) retards growth and promotes excessive neutral lipid storage. Gene expression analysis reveals that dietary S. maltophilia induces a lipogenic transcriptional response that includes the SREBP ortholog SBP-1, and fatty acid desaturases FAT-6 and FAT-7. Live imaging and ultrastructural analysis suggest that excess neutral lipid is stored in greatly expanded lipid droplets (LDs), as a result of enhanced endoplasmic reticulum (ER)-LD interaction. We also report that loss of function mutations in dpy-9 in C. elegans confers resistance to S. maltophilia. Dietary S. maltophilia induces supersized LDs by enhancing lipogenesis and ER-LD contacts in C. elegans. This work delineates a new model for understanding microbial regulation of metazoan physiology.

Automated summary

Dietary and symbiotic bacteria have a significant impact on metazoan lipid metabolism, but the mechanisms by which bacteria influence lipid storage in their host are still unknown. This study used Caenorhabditis elegans as a model organism to investigate the interaction between gut microbiota and the host. The results showed that feeding C. elegans with Stenotrophomonas maltophilia (S. maltophilia) bacteria retarded growth and promoted excessive neutral lipid storage. Gene expression analysis revealed a lipogenic response induced by dietary S. maltophilia. Furthermore, it was observed that excess neutral lipid was stored in expanded lipid droplets due to enhanced endoplasmic reticulum (ER)-lipid droplet interactions. The study also identified a gene mutation in C. elegans that conferred resistance to S. maltophilia. This work provides a new model for understanding how microbes regulate metazoan physiology.