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1. Gut microbiota metabolically mediate intestinal helminth infection in zebrafish

   https://doi.org/10.1128/msystems.00545-24  

   Hammer, Austin J; Gaulke, Christopher A; Garcia-Jaramillo, Manuel; Leong, Connor; Morre, Jeffrey; Sieler_Jr, Michael J; Stevens, Jan F; Jiang, Yuan; Maier, Claudia S; Kent, Michael L; et al (September 2024, mSystems)

   Rawls, John F (Ed.)

   ABSTRACT Intestinal helminth parasite (IHP) infection induces alterations in the composition of microbial communities across vertebrates, although how gut microbiota may facilitate or hinder parasite infection remains poorly defined. In this work, we utilized a zebrafish model to investigate the relationship between gut microbiota, gut metabolites, and IHP infection. We found that extreme disparity in zebrafish parasite infection burden is linked to the composition of the gut microbiome and that changes in the gut microbiome are associated with variation in a class of endogenously produced signaling compounds, N-acylethanolamines, that are known to be involved in parasite infection. Using a statistical mediation analysis, we uncovered a set of gut microbes whose relative abundance explains the association between gut metabolites and infection outcomes. Experimental investigation of one of the compounds in this analysis reveals salicylaldehyde, which is putatively produced by the gut microbePelomonas, as a potent anthelmintic with activity againstPseudocapillaria tomentosaegg hatching, bothin vitroandin vivo. Collectively, our findings underscore the importance of the gut microbiome as a mediating agent in parasitic infection and highlight specific gut metabolites as tools for the advancement of novel therapeutic interventions against IHP infection. IMPORTANCEIntestinal helminth parasites (IHPs) impact human health globally and interfere with animal health and agricultural productivity. While anthelmintics are critical to controlling parasite infections, their efficacy is increasingly compromised by drug resistance. Recent investigations suggest the gut microbiome might mediate helminth infection dynamics. So, identifying how gut microbes interact with parasites could yield new therapeutic targets for infection prevention and management. We conducted a study using a zebrafish model of parasitic infection to identify routes by which gut microbes might impact helminth infection outcomes. Our research linked the gut microbiome to both parasite infection and to metabolites in the gut to understand how microbes could alter parasite infection. We identified a metabolite in the gut, salicylaldehyde, that is putatively produced by a gut microbe and that inhibits parasitic egg growth. Our results also point to a class of compounds, N-acyl-ethanolamines, which are affected by changes in the gut microbiome and are linked to parasite infection. Collectively, our results indicate the gut microbiome may be a source of novel anthelmintics that can be harnessed to control IHPs. 

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2. New approaches to secondary metabolite discovery from anaerobic gut microbes

   https://doi.org/10.1007/s00253-024-13393-y  

   Butkovich, Lazarina_V; Vining, Oliver_B; O’Malley, Michelle_A (January 2025, Applied Microbiology and Biotechnology)

   AbstractThe animal gut microbiome is a complex system of diverse, predominantly anaerobic microbiota with secondary metabolite potential. These metabolites likely play roles in shaping microbial community membership and influencing animal host health. As such, novel secondary metabolites from gut microbes hold significant biotechnological and therapeutic interest. Despite their potential, gut microbes are largely untapped for secondary metabolites, with gut fungi and obligate anaerobes being particularly under-explored. To advance understanding of these metabolites, culture-based and (meta)genome-based approaches are essential. Culture-based approaches enable isolation, cultivation, and direct study of gut microbes, and (meta)genome-based approaches utilizeinsilicotools to mine biosynthetic gene clusters (BGCs) from microbes that have not yet been successfully cultured. In this mini-review, we highlight recent innovations in this area, including anaerobic biofoundries like ExFAB, the NSF BioFoundry for Extreme & Exceptional Fungi, Archaea, and Bacteria. These facilities enable high-throughput workflows to study oxygen-sensitive microbes and biosynthetic machinery. Such recent advances promise to improve our understanding of the gut microbiome and its secondary metabolism. Key points• Gut microbial secondary metabolites have therapeutic and biotechnological potential• Culture- and (meta)genome-based workflows drive gut anaerobe metabolite discovery• Anaerobic biofoundries enable high-throughput workflows for metabolite discovery Graphical abstract 

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3. Standardized multi-omics of Earth’s microbiomes reveals microbial and metabolite diversity

   https://doi.org/10.1038/s41564-022-01266-x  

   Shaffer, Justin P.; Nothias, Louis-Félix; Thompson, Luke R.; Sanders, Jon G.; Salido, Rodolfo A.; Couvillion, Sneha P.; Brejnrod, Asker D.; Lejzerowicz, Franck; Haiminen, Niina; Huang, Shi; et al (December 2022, Nature Microbiology)

   Despite advances in sequencing, lack of standardization makes comparisons across studies challenging and hampers insights into the structure and function of microbial communities across multiple habitats on a planetary scale. Here we present a multi-omics analysis of a diverse set of 880 microbial community samples collected for the Earth Microbiome Project. We include amplicon (16S, 18S, ITS) and shotgun metagenomic sequence data, and untargeted metabolomics data (liquid chromatography-tandem mass spectrometry and gas chromatography mass spectrometry). We used standardized protocols and analytical methods to characterize microbial communities, focusing on relationships and co-occurrences of microbially related metabolites and microbial taxa across environments, thus allowing us to explore diversity at extraordinary scale. In addition to a reference database for metagenomic and metabolomic data, we provide a framework for incorporating additional studies, enabling the expansion of existing knowledge in the form of an evolving community resource. We demonstrate the utility of this database by testing the hypothesis that every microbe and metabolite is everywhere but the environment selects. Our results show that metabolite diversity exhibits turnover and nestedness related to both microbial communities and the environment, whereas the relative abundances of microbially related metabolites vary and co-occur with specific microbial consortia in a habitat-specific manner. We additionally show the power of certain chemistry, in particular terpenoids, in distinguishing Earth’s environments (for example, terrestrial plant surfaces and soils, freshwater and marine animal stool), as well as that of certain microbes including Conexibacter woesei (terrestrial soils), Haloquadratum walsbyi (marine deposits) and Pantoea dispersa (terrestrial plant detritus). This Resource provides insight into the taxa and metabolites within microbial communities from diverse habitats across Earth, informing both microbial and chemical ecology, and provides a foundation and methods for multi-omics microbiome studies of hosts and the environment. 

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4. Fine scale transitions of the microbiota and metabolome along the gastrointestinal tract of herbivorous fishes

   https://doi.org/10.1186/s42523-022-00182-z  

   Sparagon, Wesley J.; Gentry, Emily C.; Minich, Jeremiah J.; Vollbrecht, Lisa; Laurens, Lieve M.; Allen, Eric E.; Sims, Neil A.; Dorrestein, Pieter C.; Kelly, Linda Wegley; Nelson, Craig E. (December 2022, Animal Microbiome)

   Abstract Background Gut microorganisms aid in the digestion of food by providing exogenous metabolic pathways to break down organic compounds. An integration of longitudinal microbial and chemical data is necessary to illuminate how gut microorganisms supplement the energetic and nutritional requirements of animals. Although mammalian gut systems are well-studied in this capacity, the role of microbes in the breakdown and utilization of recalcitrant marine macroalgae in herbivorous fish is relatively understudied and an emerging priority for bioproduct extraction. Here we use a comprehensive survey of the marine herbivorous fish gut microbial ecosystem via parallel 16S rRNA gene amplicon profiling (microbiota) and untargeted tandem mass spectrometry (metabolomes) to demonstrate consistent transitions among 8 gut subsections across five fish of the genus of Kyphosus . Results Integration of microbial phylogenetic and chemical diversity data reveals that microbial communities and metabolomes covaried and differentiated continuously from stomach to hindgut, with the midgut containing multiple distinct and previously uncharacterized microenvironments and a distinct hindgut community dominated by obligate anaerobes. This differentiation was driven primarily by anaerobic gut endosymbionts of the classes Bacteroidia and Clostridia changing in concert with bile acids, small peptides, and phospholipids: bile acid deconjugation associated with early midgut microbiota, small peptide production associated with midgut microbiota, and phospholipid production associated with hindgut microbiota. Conclusions The combination of microbial and untargeted metabolomic data at high spatial resolution provides a new view of the diverse fish gut microenvironment and serves as a foundation to understand functional partitioning of microbial activities that contribute to the digestion of complex macroalgae in herbivorous marine fish. 

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5. Gut microbiota contribute to variations in honey bee foraging intensity

   https://doi.org/10.1093/ismejo/wrae030  

   Vernier, Cassondra L; Nguyen, Lan Anh; Gernat, Tim; Ahmed, Amy Cash; Chen, Zhenqing; Robinson, Gene E (February 2024, The ISME Journal)

   Abstract Gut microbiomes are increasingly recognized for mediating diverse biological aspects of their hosts, including complex behavioral phenotypes. Although many studies have reported that experimental disruptions to the gut microbial community result in atypical host behavior, studies that address how gut microbes contribute to adaptive behavioral trait variation are rare. Eusocial insects represent a powerful model to test this, because of their simple gut microbiota and complex division of labor characterized by colony-level variation in behavioral phenotypes. Although previous studies report correlational differences in gut microbial community associated with division of labor, here, we provide evidence that gut microbes play a causal role in defining differences in foraging behavior between European honey bees (Apis mellifera). We found that gut microbial community structure differed between hive-based nurse bees and bees that leave the hive to forage for floral resources. These differences were associated with variation in the abundance of individual microbes, including Bifidobacterium asteroides, Bombilactobacillus mellis, and Lactobacillus melliventris. Manipulations of colony demography and individual foraging experience suggested that differences in gut microbial community composition were associated with task experience. Moreover, single-microbe inoculations with B. asteroides, B. mellis, and L. melliventris caused effects on foraging intensity. These results demonstrate that gut microbes contribute to division of labor in a social insect, and support a role of gut microbes in modulating host behavioral trait variation. 

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