261B Poster - 02. Immunity and the microbiome
Friday April 08, 2:00 PM - 4:00 PM

Authors:
Haolong Zhu ^1,2; Allan Spradling ^1,2,3; William Ludington ^1,2

Affiliations:
1) Department of Embryology, Carnegie Institution for Science, Baltimore, MD; 2) Department of Biology, Johns Hopkins University, Baltimore, MD; 3) Howard Hughes Medical Institute, Chevy Chase, MD

Keywords:
m. microbiome; k. host/pathogen interactions

A mechanistic understanding of gut microbiome colonization is fundamental to understanding the microbiome’s functions and its physiological relevance. Specific associations with certain microbiome species in a host’s gastrointestinal tract have been consistently observed among many animal species including fruit flies, mice, and humans. However, little is known about how these specific microbiome species are chosen for stable colonization and how such specificity is determined.

We hypothesize that the host gut actively promotes stable microbiome colonization with appropriate species via the molecular production of the appropriate environment, termed the “commensal niche.” Maintaining the commensal niche for certain microbiome species can be physiologically important for effective food digestion, efficient nutrition absorption, and enhanced immunity.

Previously, we isolated the fly gut microbiome strain, L. plantarum (LpWF), from a wild fruit fly. The strain preferentially colonizes the fly foregut region, in particular the proventriculus inner lumen, with high stability, suggesting a commensal niche for LpWF is produced by the fly. We took advantage of this strong colonization phenotype to ask how the commensal niche for LpWF is developed and maintained at the cellular and molecular levels. We applied bulk and single-cell RNAseq to profile the transcriptional changes in the spatially defined commensal niche over time to identify specific cellular and molecular components essential for appropriate microbiome colonization. We are evaluating the identified candidates through loss-of-function and gain-of-function experiments.

In summary, our study seeks to decipher the molecular basis of gut microbiome colonization and how it benefits the host. Such a mechanistic understanding is likely analogous to other host-microbiome interactions as a general paradigm and could enable the design of intervening strategies for a probiotic gut microbiome that benefits human health.