About

Seth Bordenstein is a professor of Biology and Entomology at Penn State, serving as the Director of the One Health Microbiome Center and holding the Huck Chair in Microbiome Sciences. His research focuses on the evolutionary and genetic principles that shape symbiotic interactions between animals, microbes, and viruses, with a particular emphasis on their applications to human health. Bordenstein's work explores the microbiome sciences within the framework of holobiont biology, uniting life’s seen and unseen realms, and advancing the understanding of host-microbe interactions, phylosymbiosis, and the microbiome's role in health and disease. He has contributed to the development of the microbiome sciences as an interdisciplinary field, leading initiatives such as the One Health Microbiome Center, which is recognized as one of the largest and most active organizations in this domain. His research has significant implications for understanding the microbiome's influence on host biology, disease risk, and ecological health.

Research topics

• Biology
• Genetics
• Evolutionary biology
• Ecology
• Computational biology
• Microbiology
• Cell biology
• Zoology

Selected publications

• Beyond timescale separation: An eco-evolutionary consumer-resource theory of host-microbe symbioses

  2026-01-28

  articleOpen access

  Symbiotic associations between microorganisms and hosts are universal and dynamic. However, current ecological and evolutionary theory often simplistically analyzes hosts and symbionts as either separate or fully integrated entities. This entrenchment obscures a central research challenge: to understand symbioses across varying degrees of interaction, integration, and functional dependence. We posit that major advances will emerge from theoretical models that explicitly capture eco-evolutionary feedbacks linking host and microbial community interaction structure, biotic resource availability, and selection across biological levels. We show how extending consumer-resource theory to incorporate evolutionary processes can overcome limitations in separation of timescales approaches, advancing our understanding of the evolution, adaptability, and persistence of variable host-microbe symbioses. By coupling ecological and evolutionary dynamics across scales, this framework can guide both basic understanding and applied approaches in symbiosis research.

  PublisherOA PDFDOI

• Extensive mobilome dynamics in a widespread endosymbiont: long read metagenomics reveal dimeric plasmids and highly fragmented prophages in Wolbachia from Culex pipiens

  Research Square · 2026-02-18

  preprintOpen access
  PublisherOA PDFDOI

• Host and Microbe Scale Processes Jointly Shape Spatial Variation in Aphaenogaster (Hymenoptera: Formicidae)associated Wolbachia

  Research Square · 2026-01-29

  preprintOpen access
  PublisherOA PDFDOI

• Ecologically expanding the One Health framework to unify the microbiome sciences

  mBio · 2025-05-12 · 9 citations

  articleOpen accessSenior author

  The One Health framework, traditionally focused on microbial threats, needs a bold expansion to include the full breadth of microbial diversity-from pathogenic to beneficial-within its ecological and evolutionary context. By shifting focus from disease surveillance to microbial stewardship, an integrative One Health microbiome science approach breaks down traditional silos in microbiome research, accelerating integrative and comparative science to uncover foundational insights into microbial community assembly, stability, and resilience. Ultimately, this will help unlock the full potential of microbiomes to enhance global health and sustainably manage ecosystems.

  PublisherDOI

• Safeguarding microbial biodiversity: microbial conservation specialist group within the species survival commission of the International Union for Conservation of Nature

  mSystems · 2025-11-20

  articleOpen access
  PublisherDOI

• <i>Wolbachia</i> and its pWCP plasmid show differential dynamics during the development of <i>Culex</i> mosquitoes

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-04

  preprintOpen access

  Abstract Mosquitoes are major vectors of pathogens such as arboviruses and parasites, causing significant health impacts each year. Wolbachia , an intracellular bacterium widely distributed among arthropods, represents a promising vector control solution. This bacterium can reduce the transmission of dengue, Zika and chikungunya arboviruses and manipulate the reproduction of its host through its prophage WO. Although research on the Wolbachia mobilome primarily focuses on WO and the phenotypes it induces, the function of Wolbachia plasmid pWCP, recently discovered and reported to be strikingly conserved worldwide, remains unknown. In this study, we analyzed the presence and abundance of pWCP as well as Wolbachia in two different species of Culex mosquitoes, one of the most widespread genera in the world and a vector of numerous diseases. We compared relative densities of the bacterium and its mobile genetic element in Culex pipiens molestus and Culex quinquefasciatus , a facultatively autogenous and a anautogenous species, respectively, throughout their development from larval stage L1 to adult individual specimen using quantitative PCR. Our results suggest that 2-5 copies of pWCP occur in Wolbachia cells on average, and the plasmid co-replicates with Wolbachia cells. Moreover, Wolbachia and pWCP exhibit differential levels of abundance at specific development stages throughout the mosquito’s life cycle in each species. These findings indicate important, and likely beneficial, roles for the plasmid in the bacterium’s biology in different mosquito species as well as complex interaction dynamics between Wolbachia and its host during its life cycle. Importance Mosquitoes of the Culex genus are critical vectors for numerous diseases, causing significant public health concerns. The intracellular bacterium Wolbachia has emerged as a promising vector control solution due to its ability to interfere with pathogen transmission and manipulate mosquito reproduction. However, unlike the extensively studied WO phage, the biological significance and function of Wolbachia’s pWCP plasmid, a recently discovered and strikingly conserved mobile genetic element in Culex species, remains unknown. This study investigates the developmental dynamics of pWCP and Wolbachia in two Culex mosquito species, Culex pipiens molestus and Culex quinquefasciatus across their life cycle. In general, the abundance levels of Wolbachia and the plasmid were found to vary across life stages and differ between the two species. However, a relatively small number of pWCP copies were observed per Wolbachia cell, together with a co-replication of the plasmid with the bacterium for most developmental stages. Altogether, these findings suggest a likely beneficial and non-parasitic role for pWCP in Wolbachia ’s biology, that may contribute to the intricate interactions between the bacterium and its mosquito hosts.

  PublisherOA PDFDOI

• Cytoplasmic incompatibility factor proteins from <i>Wolbachia</i> prophage are costly to sperm development in <i>Drosophila melanogaster</i>

  Proceedings of the Royal Society B Biological Sciences · 2025-02-01 · 1 citations

  articleOpen accessSenior authorCorresponding

  The symbiosis between arthropods and Wolbachia bacteria is globally widespread, largely due to selfish-drive systems that favour the fitness of symbiont-transmitting females. The most common drive, cytoplasmic incompatibility (CI), is central to arboviral control efforts. In Drosophila melanogaster carrying w Mel Wolbachia deployed in mosquito control, two prophage genes in Wolbachia, cifA and cifB , cause CI that results in a paternal-effect lethality of embryos in crosses between Wolbachia -bearing males and aposymbiotic females. While the CI mechanism by which Cif proteins alter sperm development has recently been elucidated in D. melanogaster and Aedes aegypti mosquitoes, the Cifs’ extended impact on male reproductive fitness such as sperm morphology and quantity remains unclear. Here, using cytochemical, microscopic and transgenic assays in D. melanogaster, we demonstrate that both CifA and CifB cause a significant portion of defects in elongating spermatids, culminating in malformed mature sperm nuclei. Males expressing Cifs have reduced spermatid bundles and sperm counts, and transgenic expression of Cifs can occasionally result in no mature sperm formation. We reflect on Cifs’ varied functional impacts on the Host Modification model of CI as well as host evolution, behaviour and vector control strategies.

  PublisherDOI

• Host and Microbe Scale Processes Shape Spatial Variation in <i>Aphaenogaster</i> (Hymenoptera: Formicidae) Genetics and Their Microbiota

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-15

  preprintOpen access

  Abstract Like all ecological communities, host-associated (HA) microbiota are shaped by environmental selection and dispersal limitation. However, unlike communities of free-living organisms, communities of HA microbes experience selection and dispersal at two separate scales – the scale of the microbes and the scale of their hosts. Thus, HA microbes must tolerate not only the environment created by their host (microbe-scale environment), but also, the environment in which their host resides (host-scale environment). Likewise, HA microbes can disperse between hosts through either horizontal or vertical transmission (microbe-scale dispersal) but can also disperse between locations through host movement (host-scale dispersal). In this paper, we examine how multiscale environmental selection and dispersal limitation shape the genetics and HA microbiota of ants in the Aphaenogaster fulva-rudis-texana (Hymenoptera: Formicidae) complex. We begin by showing how spatial variation in Aphaenogaster genetics is shaped by host-scale environmental selection and dispersal limitation. We then show how this allows both host- and microbe-scale environmental selection to govern spatial variation in Aphaenogaster microbiota. Finally, we discuss the possibility that microbe-scale dispersal limitation also impacts spatial variation in Aphaenogaster microbiota and that this, in turn, may contribute to spatial variation in Aphaenogaster genetics. Ultimately, our results help to shed light on the myriad of interacting factors governing spatial variation in HA microbiota, including the potential for complex, bidirectional interactions between host- and microbe-scale processes.

  PublisherOA PDFDOI

• Safeguarding microbial biodiversity: microbial conservation specialist group within the species survival commission of the International Union for Conservation of Nature

  The ISME Journal · 2025-01-01 · 5 citations

  articleOpen access
  PublisherOA PDFDOI

• Gut fungi are associated with human genetic variation and disease risk

  PLoS Biology · 2025-09-02

  articleOpen accessSenior authorCorresponding

  Human genetic determinants of the gut mycobiome remain uninvestigated despite decades of research highlighting tripartite relationships between gut bacteria, genetic background, and disease. Here, we present the first genome-wide association study on the number and types of human genetic loci influencing gut fungi relative abundance. We detect 148 fungi-associated variants (FAVs) across 7 chromosomes that statistically associate with 9 fungal taxa. Of these FAVs, several occur in the protein-coding genes PTPRC, ANAPC10, NAV2, and CDH13. Additional FAVs link to tissue-specific gene expression as fungi-associated expression quantitative trait loci. Notably, the relative abundance of gut yeast Kazachstania associates with genetic variation in CDH13 encoding T-cadherin, a protein linked to cardiovascular disease. Kazachstania forms a causal relationship with cardiovascular disease risk in a mendelian two-sample randomization analysis. These findings establish previously unrecognized connections between human genetics, gut fungi, and chronic disease, broadening the paradigm of human-microbe interactions in the gut to the mycobiome.

  PublisherOA PDFDOI

Recent grants

• Dimensions: The Microbial Basis of Animal Speciation

  NSF · $1.3M · 2011–2017

• Wolbachia Genes that Mediate Male Killing

  NIH · $421k · 2017–2020

• Wolbachia Genes That Mediate Cytoplasmic Incompatibility

  NIH · $432k · 2016–2018

• The Genetic Architecture of Maternal Supression of Symbionts

  NSF · $958k · 2015–2020

• NIH Grant R01GM08516301

  NIH · $246k · 2013

Frequent coauthors

• J. Dylan Shropshire

  Vanderbilt University

  43 shared

• Brittany A. Leigh

  Vanderbilt University

  42 shared

• Sarah R. Bordenstein

  Pennsylvania State University

  39 shared

• Robert M. Brucker

  Harvard University

  27 shared

• Rupinder Kaur

  Pennsylvania State University

  27 shared

• John H. Werren

  University of Rochester

  24 shared

• Andrew Brooks

  United Nations Children's Fund

  24 shared

• Elizabeth K. Mallott

  Washington University in St. Louis

  23 shared

Labs

• One Health Microbiome CenterPI

Awards & honors

• Fellow of the American Association for the Advancement of Sc…
• Inaugural Microbiome Medal (2025)