{
  "abstract": "Severe pneumonia-associated lung injury is a major cause of acute respiratory failure, acute respiratory distress syndrome (ARDS), and death in critically ill patients. Its course is shaped within the critically ill host environment by pulmonary infection and tissue injury, systemic inflammation, circulatory and organ dysfunction, host reserve, and ICU treatment exposures, and may be accompanied by changes in gut microbiota, barrier integrity, and cellular immune metabolism. Thus, pulmonary, intestinal, circulatory, and metabolic changes should be viewed as interrelated processes occurring at different physiological levels rather than as a predefined linear pathway. Emerging studies suggest links among gut microbiota remodeling, barrier disruption, microbial or host-derived circulating signals, altered microbial metabolites, and immune-cell metabolic reprogramming. However, their biological significance varies. Some may represent parallel responses to severe infection and critical illness, whereas others may arise secondary to lung injury, hypoxia, hypoperfusion, or treatment exposure. Longitudinal human evidence remains insufficient to establish whether gut-derived signals achieve physiologically effective remote exposure and independently modify lung injury. Mechanical ventilation is essential for severe respiratory failure, and its direct mechanical contribution to ventilator-induced lung injury has a relatively clear physiological basis. In contrast, sedation, hemodynamic and splanchnic perfusion changes, oxygenation and ventilation status, antibiotics, and nutritional support are distinct concomitant exposures that may independently influence gastrointestinal function, microbiota, barrier integrity, and immune metabolism. Using the critically ill host response as the overarching framework, this review evaluates the temporality, directionality, and functional support of relationships among gut microbiota, barrier function, candidate remote signals, cellular immune metabolism, and ventilation-related exposures, and assesses whether current evidence supports biologically and clinically meaningful gut-lung-immune-metabolic interactions. It also discusses lung-protective ventilation, nutritional support, microbiota modulation, anti-inflammatory therapy, and barrier protection. Current evidence derives mainly from limited studies in severe pneumonia or pneumonia-associated ARDS, clinical evidence from other critically ill populations, and preclinical studies. Evidence that pulmonary and systemic critical illness responses affect the gut is stronger than evidence for an independent gut-to-lung effect. Future longitudinal multi-compartment studies, source tracing, multi-omics integration, and mechanism-oriented interventions are needed to clarify functional cross-compartment relationships and their incremental clinical value for risk stratification and targeted treatment.",
  "abstract_shown": true,
  "affiliations": [
    "Gansu Provincial Maternity and Child Care Hospital",
    "Gansu Provincial Maternity and Child Care Hospital (Gansu Provincial Central Hospital)"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Cheng Cheng"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xia ping Xiao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lei Zhang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "De Chen"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ling Lu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ying Liu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Song Du"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9feqcvntnwmwm.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1914644",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13733288/",
  "id": "9feqcvntnwmwm",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1914644/full",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Review"
    ],
    [
      "openalex",
      "2706|Nosocomial Infections in ICU"
    ]
  ],
  "openalex": "W7223109732",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1914644/pdf",
  "pmcid": "PMC13733288",
  "pmid": "42985158",
  "published": "2026-10-21",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/9feqcvntnwmwm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1914644",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1914644/full"
    },
    {
      "first_seen": "2026-11-08T12:23:07Z",
      "native_id": "PMC13733288",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fimmu.2026.1914644"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:1664-3224",
      "subfield": "immunology"
    }
  ],
  "title": "Severe pneumonia-associated lung injury: gut-lung-immune-metabolic connections in the critically ill host environment-microecology, barrier function, and mechanical ventilation",
  "title_text": "Severe pneumonia-associated lung injury: gut-lung-immune-metabolic connections in the critically ill host environment-microecology, barrier function, and mechanical ventilation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:23:07Z",
  "url": "https://research.draconitic.com/paper/9feqcvntnwmwm",
  "venue": "Frontiers in Immunology",
  "versions": []
}