The swine IsoLoop model of the gut host-microbiota interface enables intra-animal treatment comparisons to advance 3R principles
Date
2025-10-25
Journal Title
Journal ISSN
Volume Title
Publisher
Gut Microbes
Abstract
Understanding gut–host microbiota interactions requires models that replicate human physiology while providing region-specific resolution, translational precision, and mini-mal animal use. To this end, we developed the IsoLoop model, a swine gut loop platform enabling intra-animal, multi-treatment comparisons. Microbiota-depleted ileal loops were surgically created in pigs, maintaining neurovascular integrity while isolating them from the anastomosed digestive tract. In Experiment 1, loops were inoculated with human fecal microbiota (HFM) or HFM combined with Peptacetobacter hiranonis. In Experiment 2, they were inoculated with Clostridioides difficile. Host–microbiota interactions were compared with respective controls in each experiment. The IsoLoop model reduced animal use by 75% compared to conventional whole-animal designs. Following antibiotic-induced depletion, loops re-established microbial diversity by day 5, despite reduced richness and loss of taxa, including Lactobacillus. HFM transplantation in microbiota-depleted loops induced robust tran-scriptomic recovery, enriched Akkermansia and Bifidobacterium, and restored specific metabolic pathways, although taxonomic and metabolic restoration remained incomplete and divergent. P. hiranonis promoted normal ileum-like metagenomic functional convergence, activated epithelial repair pathways, and increased specific secondary bile acids. C. difficile challenge recapitulated early infection pathology in IsoLoops. The IsoLoop model offers an ethical and precise platform for investigating host–microbiota crosstalk, localized enteric pathologies, and therapeutic interventions.
Description
This article was originally published in Gut Microbes. The version of record is available at: https://doi.org/10.1080/19490976.2025.2568706
© 2025 The Author(s). Published with license by Taylor & Francis Group, LLC. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
Keywords
Animal model, gut host-microbiota interface, 3Rprinciples, human fecalmicrobiota, P. hiranonis, C.difficile
Citation
Bayne, J., Charavaryamath, C., Hu, Y., Yousefi, F., Murphy, M., Law, A., … Mooyottu, S. (2025). The swine IsoLoop model of the gut host-microbiota interface enables intra-animal treatment comparisons to advance 3R principles. Gut Microbes, 17(1). https://doi.org/10.1080/19490976.2025.2568706