Biology subjects

Kent, M. L.

Publications and source records attributed to Kent, M. L..

4 recordsLinked to original sources

bioRxiv2026

Historical contingency shapes zebrafish host-microbiome responses to a subsequent biotic challenge

Environmental change exposes ecosystems, including host-associated microbiomes, to stressors that occur repeatedly and in sequence, yet it remains unclear whether prior stressor history conditions host-microbiome responses to later perturbation. We used adult zebrafish (Danio rerio) to test whether sequential exposure to antibiotics, heat stress, the intestinal nematode Pseudocapillaria tomentosa, or pairwise stressor combinations altered gut microbiome structure, intestinal host gene expression, and host health outcomes. Across eight exposure regimes, prior stressor history and parasite exposure were associated with gut microbiome composition, while increasing prior stressor history was associated with reduced gut microbial diversity and convergence in community composition. Host intestinal transcriptional responses to parasite exposure were historically contingent, with parasite-associated differential gene expression varying non-linearly across prior stressor histories. Cumulative mortality increased with prior stressor history, whereas infection prevalence among surviving hosts decreased. Integrating microbial abundance, host gene expression, mortality, and neutral-community modeling identified Cetobacterium, Culicoidibacter, Flavobacterium, and Shewanella as candidate host-linked taxa associated with host response and survival. Collectively, these findings indicate that prior environmental stressor history shapes vertebrate host-microbiome responses to future perturbation and highlight specific gut microbial members as potential biomarkers or functional targets for follow-up studies.

ecology↗

bioRxiv2025

Pseudocapillaria tomentosa Infections in Laboratory Larval and Adult Zebrafish (Danio rerio): Development and Advances in an In Vivo Anthelmintic Drug Discovery Model

Parasite resistance is an increasing problem in livestock and companion animals. Developing new drug discovery models may improve the identification of novel anthelmintic drugs which will reduce parasite infections. Adult zebrafish (Danio rerio) have been previously used as a model for anthelmintic drug discovery by infecting them with the gastrointestinal nematode Pseudocapillaria tomentosa. Using larval zebrafish will increase assay sensitivity and throughput because this in vivo platform evaluates host parasite interactions and is conducted in multi-well plates. To develop this assay, this study focuses on 1) evaluating infections in 5-30 days post fertilization (dpf) fish, 2) validating the assay with a known anthelmintic used in domestic animals, and 3) documenting the growth and development of P. tomentosa. 30 dpf fish had the most robust infections in multi-well plates and the best survival compared to younger larvae. Assay sensitivity was evaluated by aqueously exposing 30 dpf infected zebrafish to emamectin benzoate (a macrocyclic lactone), which successfully reduced infection intensity. In vitro larvae hatched from eggs, larval, and adult zebrafish (n=488) were used to document P. tomentosa development from 1-37 days post exposure. A change point analysis (CPA) predicted the ecdysis (molting) points as follows (mm): L1/L2 = 0.220, L2/L3 = 0.571, L3/L4 = 1.174, and L4/L5 = 1.584. Identifying the worm molts sizes enables the inclusion of developmental endpoints within trials. Overall, this study will increase the sensitivity of anthelmintic drug discovery because the validated high throughput larval zebrafish model accounts for drug interactions between the host and parasite. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=174 SRC="FIGDIR/small/672915v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1768676org.highwire.dtl.DTLVardef@75dadcorg.highwire.dtl.DTLVardef@173dd3forg.highwire.dtl.DTLVardef@1c28722_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

Modelling the zebrafish gut microbiome's resistance and sensitivity to climate change and parasite infection

As climate change increases global water temperatures, ecologists expect intestinal helminth infection ranges to expand and increase the health burden on aquatic organisms. However, the gut microbiome can interact with these parasites to influence infection outcomes, raising the possibility that its response to increasing temperatures may help buffer against increased infection burden. To evaluate this hypothesis, we sought to determine if the microbiome is resistant or resilient to the stressors of increased water temperature, helminth exposure, and their combination, and whether this variation linked to infection outcomes. We leveraged the zebrafish (Danio rerio) model organism to measure how these variables relate to the temporal dynamics of the gut microbiome. In particular, we exposed adult zebrafish to the parasitic whipworm Pseudocapillaria tomentosa across three different water temperatures (28{degrees}C, 32{degrees}C, 35{degrees}C), and analyzed fecal microbiome samples at five time points across 42 days. Our findings show that parasite exposure and water temperature independently alter gut microbiome diversity. Moreover, we find that water temperature moderates the association between parasite infection and the gut microbiome. Consistent with this observation, but at odds with current expectations, we find that increasing water temperature reduces parasitic infection in fish. Overall, our results indicate that water temperature alters the contextual landscape of the gut microbiome to impact its response to an exogenous stressor of an intestinal parasite in zebrafish. Furthermore, our findings represent the first report of the effects of elevated temperature on parasitic nematode development in a fish host. Importantly, our study demonstrates that climate change may have unanticipated and environmentally contingent impacts to vertebrate gut microbiomes and health outcomes in response to an exogenous stressor.

microbiology↗

bioRxiv2024

Gut microbiota metabolically mediate intestinal helminth infection in Zebrafish

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 microbe Pelomonas, as a potent anthelmintic with activity against Pseudocapillaria tomentosa egg hatching, both in vitro and in vivo. Collectively, our findings underscore the importance of the gut microbiome as a mediating agent in parasitic infection and highlights 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 which can be harnessed to control IHPs.

microbiology↗