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1. Evaluating supervised and unsupervised background noise correction in human gut microbiome data

   https://doi.org/10.1371/journal.pcbi.1009838  

   Briscoe, Leah; Balliu, Brunilda; Sankararaman, Sriram; Halperin, Eran; Garud, Nandita R. (February 2022, PLOS Computational Biology)

   Segata, Nicola (Ed.)

   The ability to predict human phenotypes and identify biomarkers of disease from metagenomic data is crucial for the development of therapeutics for microbiome-associated diseases. However, metagenomic data is commonly affected by technical variables unrelated to the phenotype of interest, such as sequencing protocol, which can make it difficult to predict phenotype and find biomarkers of disease. Supervised methods to correct for background noise, originally designed for gene expression and RNA-seq data, are commonly applied to microbiome data but may be limited because they cannot account for unmeasured sources of variation. Unsupervised approaches address this issue, but current methods are limited because they are ill-equipped to deal with the unique aspects of microbiome data, which is compositional, highly skewed, and sparse. We perform a comparative analysis of the ability of different denoising transformations in combination with supervised correction methods as well as an unsupervised principal component correction approach that is presently used in other domains but has not been applied to microbiome data to date. We find that the unsupervised principal component correction approach has comparable ability in reducing false discovery of biomarkers as the supervised approaches, with the added benefit of not needing to know the sources of variation apriori. However, in prediction tasks, it appears to only improve prediction when technical variables contribute to the majority of variance in the data. As new and larger metagenomic datasets become increasingly available, background noise correction will become essential for generating reproducible microbiome analyses. 

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2. Understanding the factors regulating host–microbiome interactions using Caenorhabditis elegans

   https://doi.org/10.1098/rstb.2023.0059  

   Singh, Anupama; Luallen, Robert J (May 2024, Philosophical Transactions of the Royal Society B: Biological Sciences)

   The Human Microbiome Project was a research programme that successfully identified associations between microbial species and healthy or diseased individuals. However, a major challenge identified was the absence of model systems for studying host–microbiome interactions, which would increase our capacity to uncover molecular interactions, understand organ-specificity and discover new microbiome-altering health interventions.Caenorhabditis eleganshas been a pioneering model organism for over 70 years but was largely studied in the absence of a microbiome. Recently, ecological sampling of wild nematodes has uncovered a large amount of natural genetic diversity as well as a slew of associated microbiota. The field has now explored the interactions ofC. eleganswith its associated gut microbiome, a defined and non-random microbial community, highlighting its suitability for dissecting host–microbiome interactions. This core microbiome is being used to study the impact of host genetics, age and stressors on microbiome composition. Furthermore, single microbiome species are being used to dissect molecular interactions between microbes and the animal gut. Being amenable to health altering genetic and non-genetic interventions,C. eleganshas emerged as a promising system to generate and test new hypotheses regarding host–microbiome interactions, with the potential to uncover novel paradigms relevant to other systems. This article is part of the theme issue ‘Sculpting the microbiome: how host factors determine and respond to microbial colonization’. 

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3. Aedes aegypti gut transcriptomes respond differently to microbiome transplants from field‐caught or laboratory‐reared mosquitoes

   https://doi.org/10.1111/1462-2920.16576  

   Hegde, Shivanand; Brettell, Laura E; Quek, Shannon; Etebari, Kayvan; Saldaña, Miguel A; Asgari, Sassan; Coon, Kerri L; Heinz, Eva; Hughes, Grant L (February 2024, Environmental Microbiology)

   Abstract The mosquito microbiome is critical for host development and plays a major role in many aspects of mosquito biology. While the microbiome is commonly dominated by a small number of genera, there is considerable variation in composition among mosquito species, life stages, and geography. How the host controls and is affected by this variation is unclear. Using microbiome transplant experiments, we asked whether there were differences in transcriptional responses when mosquitoes of different species were used as microbiome donors. We used microbiomes from four different donor species spanning the phylogenetic breadth of the Culicidae, collected either from the laboratory or the field. We found that when recipients received a microbiome from a donor reared in the laboratory, the response was remarkably similar regardless of donor species. However, when the donor had been collected from the field, many more genes were differentially expressed. We also found that while the transplant procedure did have some effect on the host transcriptome, this is likely to have had a limited effect on mosquito fitness. Overall, our results highlight the possibility that variation in mosquito microbiome communities is associated with variability in host–microbiome interactions and further demonstrate the utility of the microbiome transplantation technique for investigating host–microbe interactions in mosquitoes. 

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4. Depuration of a solitary ascidian depletes transient bacteria without altering microbiome alpha-diversity

   https://doi.org/10.1093/femsec/fiaf078  

   Hutchings, Brenna; López-Legentil, Susanna; Stefaniak, Lauren M; Nydam, Marie L; Erwin, Patrick M (July 2025, FEMS Microbiology Ecology)

   Abstract Depuration, or the process of clearing impurities from the gut, is commonly applied to marine food products due to its efficacy in removing human pathogens from shellfish and edible ascidians. Recent studies also reported that depuration of filter-feeding animals helped reduce transient bacteria and identify resident symbionts in gut microbiome studies. Here, we examined the impact of depuration on bacteria in the branchial sac, gut, and hepatic gland of the solitary ascidian Pyura vittata. Replicates were kept in filtered seawater for 4 days prior to dissection (aquaria-depuration) and compared to samples that were immediately processed following collection (wild-no depuration) and replicates kept in unfiltered seawater for 4 days (aquaria-control). 16S rRNA gene sequence analysis revealed no significant differences among ascidian sources for microbial alpha-diversity but significant shifts in beta-diversity. Depuration reduced the number of core bacteria markedly (66%–84%) across all body regions, and bacteria that remained postdepuration consisted of genera associated with enhanced host health and resilience within other marine symbioses. Our results suggest that microbial profiles obtained following depuration do not substantially differ from those of nondepurated animals, but depuration can help differentiate transient from core and resident taxa in complex host–microbiome symbioses. 

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5. Disentangling the link between zebrafish diet, gut microbiome succession, and Mycobacterium chelonae infection

   https://doi.org/10.1186/s42523-023-00254-8  

   Sieler, Michael J; Al-Samarrie, Colleen E; Kasschau, Kristin D; Varga, Zoltan M; Kent, Michael L; Sharpton, Thomas J (December 2023, Animal Microbiome)

   Abstract BackgroundDespite the long-established importance of zebrafish (Danio rerio) as a model organism and their increasing use in microbiome-targeted studies, relatively little is known about how husbandry practices involving diet impact the zebrafish gut microbiome. Given the microbiome’s important role in mediating host physiology and the potential for diet to drive variation in microbiome composition, we sought to clarify how three different dietary formulations that are commonly used in zebrafish facilities impact the gut microbiome. We compared the composition of gut microbiomes in approximately 60 AB line adult (129- and 214-day-old) zebrafish fed each diet throughout their lifespan. ResultsOur analysis finds that diet has a substantial impact on the composition of the gut microbiome in adult fish, and that diet also impacts the developmental variation in the gut microbiome. We further evaluated how 214-day-old fish microbiome compositions respond to exposure of a common laboratory pathogen,Mycobacterium chelonae, and whether these responses differ as a function of diet. Our analysis finds that diet determines the manner in which the zebrafish gut microbiome responds toM. chelonaeexposure, especially for moderate and low abundance taxa. Moreover, histopathological analysis finds that male fish fed different diets are differentially infected byM. chelonae. ConclusionsOverall, our results indicate that diet drives the successional development of the gut microbiome as well as its sensitivity to exogenous exposure. Consequently, investigators should carefully consider the role of diet in their microbiome zebrafish investigations, especially when integrating results across studies that vary by diet. 

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