{"doi":"10.1242/dev.204884","title":"In preprints: are microbes the architects of animal bodies?","abstract":"Microbes have been with us from the very beginning, shaping the evolutionary trajectory of animals (McFall-Ngai et al., 2013). As a result, developmental mechanisms may have not only evolved in their presence but also been molded by them (Rosenberg and Zilber-Rosenberg, 2011). The microbiota is a diverse array of microorganisms that form spatially distinct ecological communities both within and on animal hosts, playing a crucial role in maintaining health. The host and its microbiota engage in constant bidirectional communication through secondary metabolites, cytokines, immune system elicitors and nutritional cues. In mammals, microbes influence the architecture of multiple organs, including the intestine, hair, skin and lungs (Bernasconi et al., 2016; Campbell and Koch, 2017; Gordon and Bruckner-Kardoss, 1961; Scharschmidt et al., 2017). Within specific microenvironments, the microbiota regulates the activity of tissue-resident stem cells, such as in the intestine (Peck et al., 2017) and lungs (Zacharias et al., 2018) by modulating developmental pathways (Nagy and Buchon, 2019).The fundamental influence of microbes extends beyond mammals. For example, in Drosophila melanogaster, although microbes are not essential for post-embryonic development, they significantly affect intestinal epithelium homeostasis and stem cell function (Broderick et al., 2014; Buchon et al., 2009). The microbiota regulates intestinal stem cell proliferation and differentiation by modulating intrinsic genetic programs, thereby sustaining proper organ architecture and tissue homeostasis (Liu et al., 2022). Similarly, in Caenorhabditis elegans, microbial-derived folates influence distal germline stem cell proliferation via the folate receptor homolog FOLR-1 (Chaudhari et al., 2016). These findings suggest that microbial impact on animal development is a deeply conserved phenomenon.A recent preprint by He and colleagues extends this concept to Hydra, a member of the Cnidaria phylum, reinforcing the notion that microbial influences on development and stem cells span deep evolutionary time (He et al., 2024 preprint). Cnidarians occupy an early-diverging position in the animal evolutionary tree, making them a key model for understanding ancestral host-microbiota interactions. Interestingly, the Hydra body is enveloped by a sugar-rich glycocalyx that facilitates microbial colonization (Bosch, 2012). Hydra maintains its size by balancing cell loss and production through distinct stem cell lineages (endodermal, ectodermal, interstitial), which give rise to differentiated cell types (Siebert et al., 2019). Additionally, Hydra possesses remarkable regenerative capabilities and reproduces asexually via budding, making it an ideal system to study stem cell behavior in both homeostasis and regeneration (Vogg et al., 2019).The findings in this preprint reveal that microbiota depletion leads to reduced budding and imbalanced epithelial cell composition in most Hydra polyps. To explore this phenomenon, the authors employed single-cell multi-omics techniques (RNA-seq and ATAC-seq) to examine cellular composition, gene expression and chromatin accessibility at high resolution. Germ-free polyps exhibited diminished expression of intrinsic gene programs, including genes involved in stem cell differentiation and pattern formation (e.g. Wnt). These defects were accompanied by global changes in chromatin accessibility during terminal stem cell differentiation, ultimately disrupting differentiation trajectories and altering cellular composition of Hydra. The study highlights the substantial influence of microbiota on host genome architecture and ancient signaling networks, raising the fundamental question: how do microbial signals propagate from external communities to the core of host cells to fine-tune developmental programs in response to environmental cues?Intriguingly, gene expression and functional analyses from this preprint suggest that autophagy could regulate buddin","journal":"Development","year":2025,"id":565945,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9477,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":851212,"name":"Péter Nagy","orcid":"0000-0002-5053-0646","position":1,"is_corresponding":false},{"id":295352,"name":"Nicolas Buchon","orcid":"0000-0003-3636-8387","position":2,"is_corresponding":false},{"id":295351,"name":"Alessandro Bonfini","orcid":"0000-0001-6642-8665","position":0,"is_corresponding":true}],"reference_count":18,"raw_metadata":null,"created_at":"2026-07-19T02:56:32.546082Z","pmid":"40366084","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}