{
  "abstract": "Traditional in vitro and in vivo models often fail to replicate the complex physiology of the human gastrointestinal (GI) tract, and consequently, do not fully capture how this environment influences the infective strategies employed by enteric pathogens. Here, we evaluate air-liquid interface (ALI) cultures and gut-on-a-chip (GoC) microfluidic systems as next-generation in vitro models (NGIMs) that recreate critical features of the human GI mucosal surface, including the mucus layer, crypt-villus architecture, and biomechanical forces that modulate enteric pathogenesis. We review their application towards bacterial, fungal, viral, and parasitic infections, highlighting novel mechanisms that were previously undetected using traditional models. Comparing the two approaches, we outline how ALI excels for studies involving mucus and for cost-effective implementation, whereas GoC systems uniquely capture peristalsis and luminal flow, revealing dynamic pathogen-host interactions. Notably, both platforms enable complex co-culturing, allowing pathogen-host-commensal dynamics to be studied in a reductionist manner. Lastly, we discuss how future efforts aimed at better mimicking the human GI tract could incorporate stromal, immune, and enteric nervous system components, while also improving accessibility and standardization. Taken together, both ALI and GoC systems offer significant opportunities to provide new insights into infection biology, while also serving as effective preclinical platforms for precision medicine and the evaluation of next-generation antimicrobial therapies.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pediatrics, BC Children’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada"
  ],
  "article_type": "Review",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Linus H. Schweizer"
    },
    {
      "name": "Ashley Gilliland"
    },
    {
      "name": "Yan Chen"
    },
    {
      "name": "Artemis Melville-Bowser"
    },
    {
      "name": "Bruce A. Vallance"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2ms3d59k6f1md.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.ppat.1014718",
  "fulltext_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014718",
  "id": "2ms3d59k6f1md",
  "issns": [
    "1553-7374",
    "1553-7366"
  ],
  "landing_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014718",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2204|3D Printing in Biomedical Research"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Body fluids/Mucus"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Digestive system/Gastrointestinal tract"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Bacterial pathogens"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Bacterial pathogens/Escherichia coli"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Bacteria/Enterobacteriaceae/Escherichia/Escherichia coli"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Bacteria/Gut bacteria"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Bacteria/Gut bacteria/Escherichia/Escherichia coli"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Body fluids/Mucus"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Body fluids/Mucus"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Digestive system/Gastrointestinal tract"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Bacterial pathogens"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Bacterial pathogens/Escherichia coli"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Model organisms/Escherichia coli"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Prokaryotic models/Escherichia coli"
    ],
    [
      "plos",
      "/Research and analysis methods/Biological cultures/Cell lines/Caco-2 cells"
    ],
    [
      "plos",
      "/Research and analysis methods/Biological cultures/Organ cultures/Organoids"
    ],
    [
      "plos",
      "/Research and analysis methods/Model organisms/Escherichia coli"
    ]
  ],
  "openalex": "W7223658407",
  "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014718&type=printable",
  "pmcid": "PMC13705594",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/2ms3d59k6f1md.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:17Z",
      "native_id": "10.1371/journal.ppat.1014718",
      "source": "plos",
      "url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014718"
    },
    {
      "first_seen": "2026-10-30T12:21:44Z",
      "native_id": "PMC:PMC13705594",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13705594"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
    }
  ],
  "title": "Rebuilding the gut: Decoding enteric pathogenesis using next-generation human in vitro models",
  "title_text": "Rebuilding the gut: Decoding enteric pathogenesis using next-generation human in vitro models",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:44Z",
  "url": "https://research.draconitic.com/paper/2ms3d59k6f1md",
  "venue": "PLOS Pathogens",
  "versions": []
}