Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2023.05.19.541527

Rat microbial biogeography and age-dependent lactic acid bacteria in healthy lungs

Zhao, L.·Cunningham, C.·Andruska, A. M.·Schimmel, K.·Ali, M. K.·Kim, D.·Gu, S.·Chang, J.·Spiekerkoetter, E.·Nicolls, M. R.
View original source ↗Export metadata ↓

Abstract

The laboratory rat emerges as a useful tool for studying the interaction between the host and its microbiome. To advance principles relevant to the human microbiome, we systematically investigated and defined a multi-tissue full lifespan microbial biogeography for healthy Fischer 344 rats. Microbial community profiling data was extracted and integrated with host transcriptomic data from the Sequencing Quality Control (SEQC) consortium. Unsupervised machine learning, Spearmans correlation, taxonomic diversity, and abundance analyses were performed to determine and characterize the rat microbial biogeography and the identification of four inter-tissue microbial heterogeneity patterns (P1-P4). The 11 body habitats harbor a greater diversity of microbes than previously suspected. Lactic acid bacteria (LAB) abundances progressively declined in lungs from breastfeed newborn to adolescence/adult and was below detectable levels in elderly rats. LABs presence and levels in lungs were further evaluated by PCR in the two validation datasets. The lung, testes, thymus, kidney, adrenal, and muscle niches were found to have age-dependent alterations in microbial abundance. P1 is dominated by lung samples. P2 contains the largest sample size and is enriched for environmental species. Liver and muscle samples were mostly classified into P3. Archaea species were exclusively enriched in P4. The 357 pattern-specific microbial signatures were positively correlated with host genes in cell migration and proliferation (P1), DNA damage repair and synaptic transmissions (P2), as well as DNA transcription and cell cycle in P3. Our study established a link between metabolic properties of LAB with lung microbiota maturation and development. Breastfeeding and environmental exposure influence microbiome composition and host health and longevity. The inferred rat microbial biogeography and pattern-specific microbial signatures would be useful for microbiome therapeutic approaches to human health and good quality of life. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/541527v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1387224org.highwire.dtl.DTLVardef@cdb7dborg.highwire.dtl.DTLVardef@1e1c7ccorg.highwire.dtl.DTLVardef@440ca_HPS_FORMAT_FIGEXP M_FIG C_FIG

Source connections

Explore related subjects

microbiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Zhao, L., Cunningham, C., Andruska, A. M., Schimmel, K., Ali, M. K., Kim, D., Gu, S., Chang, J., Spiekerkoetter, E., Nicolls, M. R.. 2023-05-20. Rat microbial biogeography and age-dependent lactic acid bacteria in healthy lungs. https://doi.org/10.1101/2023.05.19.541527

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Cell cycle progression and stalked cell morphogenesis in Caulobacter crescentus are regulated independently by the flagellum

Bacteria colonize surfaces and form biofilms to survive in stressful environmental conditions. Many bacteria use an appendage called the flagellum to sense surface contact, and responding to these mechanical cues triggers rapid physiological changes to promote downstream attachment. Bacteria are known to secrete adhesins and alter their motility behavior to facilitate surface colonization, but these changes alone are insufficient to explain the breadth of adaptations observed in surface-attached cells. Disrupting flagellar assembly in the bacterium Caulobacter crescentus constitutively activates the surface sensing pathway, and this gain-of-function phenotype was previously used to identify a suite of flagellar signaling suppressor (fss) genes that promotes surface adhesion downstream of the flagellum. We show herein that a subset of fss genes also regulates the C. crescentus developmental program. Live-cell microscopy analysis of fss mutants identified independent sub-pathways that target stalked cell morphogenesis and cell cycle progression. We identify the predicted chemotaxis genes fssD and fssE as novel regulators of stalked cell morphogenesis and show that these genes act to stimulate the diguanylate cyclase PleD in flagellar assembly mutants. A separate pathway that includes the stator protein MotB and the recently characterized dNTPase FssC regulates entry into S phase downstream of the flagellum. We show that motB regulates cell cycle progression specifically in response to surface cues, and that stator-dependent cell cycle control occurs independently of c-di-GMP and CtrA. This work clarifies the downstream targets of the surface sensing network and establishes a comprehensive model for how surface sensing influences the C. crescentus developmental program.

microbiology↗
bioRxiv2026

Polyphyletic origins and lineage-specific expansion of chemosensory systems in phylum Actinomycetota

Phylum Actinomycetota (syn. Actinobacteriota or Actinobacteria), one of the largest well-studied bacterial phyla, is renowned for complex morphology, non-motility, ecological versatility, and secondary metabolite production. Chemosensory systems (CSS) are among the most sophisticated prokaryotic signal transduction architectures, yet their evolutionary distribution in this phylum remains poorly understood. Here, a comparative genomic analysis of 693 high-quality genomes spanning the phylum resolves the diversity, distribution, and evolutionary trajectories of CSS. Despite extensive genomic complexity and ecological versatility, only 6.9% of genomes encode complete CSS clusters, confined to a subset of lineages within a few classes, indicating lineage-specific retention or loss. In contrast, two-component systems (TCS) are ubiquitously abundant, with hybrid kinases enriched in CSS-deficient classes, suggesting functional compensation for the absence of dedicated chemosensory pathways. Basal lineages retain simplified CSS (F1 or F5), whereas Actinomycetes show lineage-specific expansion into multiple classes (F5, F8, F9, and ACF), often co-occurring, indicative of enhanced sensory complexity. The phylogeny of CheA homologs shows a polyphyletic distribution, supporting a mosaic evolutionary history shaped by multiple independent acquisitions, diversification, and gene loss. Collectively, our findings show that, unlike motile bacteria, members of Actinomycetota rely predominantly on TCS-driven regulatory networks, with CSS retained only in select lineages where ecological demands require enhanced environmental sensing. This work provides a phylum-wide evolutionary framework for the emergence, diversification, and functional specialization of CSS in non-motile bacteria.

microbiology↗
bioRxiv2026

Seasonal H1N1 influenza A virus preferentially infects a pre-existing ciliogenesis-primed secretory cell state

Influenza A viruses (IAV) infect secretory and ciliated cells of the human airway epithelium , but whether all cells within one cell type are equally susceptible to infection remains unresolved. Here, single-cell RNA sequencing analysis of primary human bronchial epithelial cultures from three donors identified preferential infection of a transcriptionally distinct subpopulation of secretory cells by seasonal H1N1 IAV A/Hawaii/70/2019 . Genes upregulated in this subpopulation showed enrichment for cilium-related gene ontology terms. In an ex post facto approach, this enrichment persisted after excluding genes differentially expressed between infected and mock-treated samples, including those identified in secretory cell-specific comparisons. Single-cell analysis further revealed no significant increase in ciliogenesis scores in infected secretory cells compared to mock infected cells at 6 hours post-infection , arguing against infection-induced activation of the canonical ciliogenesis programme during the initial viral replication cycle . Collectively, these results support preferential infection of ciliogenesis-primed secretory cells and refine IAV tropism beyond cell type to encompass epithelial differentiation state.

microbiology↗