William

Ludington

Gut bacteria are prevalent throughout the Metazoa and form complex microbial communities associated with food breakdown, nutrient provision and disease prevention. How hosts acquire and maintain a consistent bacterial flora remains mysterious even in the best-studied animals, including humans, mice, fishes, squid, bugs, worms and flies. This essay visits the evidence that hosts have co-evolved relationships with specific bacteria and that some of these relationships are supported by specialized physical niches that select, sequester and maintain microbial symbionts. Genetics approaches could uncover the mechanisms for recruiting and maintaining the stable and consistent members of the microbiome.This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'.

Gut bacteria are prevalent throughout the Metazoa and form complex microbial communities associated with food breakdown, nutrient provision and disease prevention. How hosts acquire and maintain a consistent bacterial flora remains mysterious even in the best-studied animals, including humans, mice, fishes, squid, bugs, worms and flies. This essay visits the evidence that hosts have co-evolved relationships with specific bacteria and that some of these relationships are supported by specialized physical niches that select, sequester and maintain microbial symbionts. Genetics approaches could uncover the mechanisms for recruiting and maintaining the stable and consistent members of the microbiome. This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'.

The animal foregut is the first tissue to encounter ingested food, bacteria, and viruses. We characterized the adult Drosophila foregut using transcriptomics to better understand how it triages consumed items for digestion or immune response and manages resources. Cell types were assigned and validated using GFP-tagged and Gal4 reporter lines. Foregut-associated neuroendocrine cells play a major integrative role by coordinating gut activity with nutrition, the microbiome, and circadian cycles; some express clock genes. Multiple epithelial cell types comprise the proventriculus, the central foregut organ that secretes the peritrophic matrix (PM) lining the gut. Analyzing cell types synthesizing individual PM layers revealed abundant mucin production close to enterocytes, similar to the mammalian intestinal mucosa. The esophagus and salivary gland express secreted proteins likely to line the esophageal surface, some of which may generate a foregut commensal niche housing specific gut microbiome species. Overall, our results imply that the foregut coordinates dietary sensing, hormonal regulation, and immunity in a manner that has been conserved during animal evolution.

A longstanding goal of biology is to identify the key genes and species that critically impact evolution, ecology, and health. Network analysis has revealed keystone species that regulate ecosystems and master regulators that regulate cellular genetic networks. Yet these studies have focused on pairwise biological interactions, which can be affected by the context of genetic background and other species present, generating higher-order interactions. The important regulators of higher-order interactions are unstudied. To address this, we applied a high-dimensional geometry approach that quantifies epistasis in a fitness landscape to ask how individual genes and species influence the interactions in the rest of the biological network. Wethen generated and also reanalyzed 5-dimensional datasets (two genetic, two microbiome). We identified key genes (e.g., the rbs locus and pykF) and species (e.g., Lactobacilli) that control the interactions of many other genes and species. These higher-order master regulators can induce or suppress evolutionary and ecological diversification by controlling the topography of the fitness landscape. Thus, we provide a method and mathematical justification for exploration of biological networks in higher dimensions.

A longstanding goal of biology is to identify the key genes and species that critically impact evolution, ecology, and health. Network analysis has revealed keystone species that regulate ecosystems and master regulators that regulate cellular genetic networks. Yet these studies have focused on pairwise biological interactions, which can be affected by the context of genetic background and other species present, generating higher-order interactions. The important regulators of higher-order interactions are unstudied. To address this, we applied a high-dimensional geometry approach that quantifies epistasis in a fitness landscape to ask how individual genes and species influence the interactions in the rest of the biological network. We then generated and also reanalyzed 5-dimensional datasets (two genetic, two microbiome). We identified key genes (e.g., the rbs locus and pykF) and species (e.g., Lactobacilli) that control the interactions of many other genes and species. These higher-order master regulators can induce or suppress evolutionary and ecological diversification by controlling the topography of the fitness landscape. Thus, we provide a method and mathematical justification for exploration of biological networks in higher dimensions.