Gut microbiota and innate immune barrier dysfunction in hepatic portal venous gas: a hypothesis-generating review
7 affiliations
- 1Department of Emergency Internal Medicine, the Affiliated Hospital of Qingdao University
- 2Complaint and Petition Office, Qingdao Traditional Chinese Medicine Hospital, Qingdao Department of Oncology, Qingdao Hiser Hospital Affiliated of Qingdao University
- 3School of the First Clinical Medicine, Shandong Second Medical University
- 4Department of Environmental Health, Qingdao Municipal Center for Disease Control and Prevention, Qingdao Institute of Preventive Medicine
- 5Department of Oncology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital)
- 6Department of Emergency Internal Medicine, Qingdao Hiser Hospital Affiliated of Qingdao University
- 7Department of Emergency Internal Medicine, Huangdao District People’s Hospital
Abstract
Hepatic portal venous gas (HPVG) is an uncommon radiographic sign whose prognosis is driven by bowel necrosis and shock rather than by intraportal gas. Immunological events along the gut–liver axis have not been synthesized for adult HPVG, and dedicated microbiome, metabolomic, gut–vascular barrier (GVB), and immune-profiling data are lacking. This hypothesis-generating review proposes gut dysbiosis as a putative contributor to mucosal and hepatic innate immune failure, inferred from cirrhosis, porto-sinusoidal vascular disease (PSVD), and intestinal ischemia/reperfusion. In those proxy states, loss of acetyl-CoA butyrate-production capacity, context-dependent bile-acid shifts, lipopolysaccharide–Toll-like receptor 4 priming, facultative-anaerobe expansion, and fermentative H ₂ /CO ₂ pathways documented in cultured HPVG isolates—Clostridium perfringens (pyruvate–ferredoxin oxidoreductase–hydrogenase) and Escherichia coli (pyruvate-formate lyase–formate hydrogen lyase)—compromise epithelial and GVB integrity. These links are not assembled as a demonstrated sequence in adult HPVG. We propose a physical-core model in which a route of entry and a local driving pressure gradient are necessary, whereas pathway-defined fermentative isolates, dysbiosis, mucosal inflammation, ischemia, and impaired portal clearance are optional amplifiers. Iatrogenic or purely pressure-related HPVG can occur without dysbiosis or a substantial pathogen-associated molecular pattern load; in necrosis-driven HPVG, dysbiosis is proposed only as a concurrent immune amplifier; when HPVG occurs in cirrhosis or PSVD, portal hypertension is treated as a host modifier of barrier geometry and washout, not as an independent generator of intraportal gas. Portal vein thrombosis, portal hypertension, pneumatosis intestinalis, pyogenic liver abscess, and HPVG may share the portal vein as a conduit but are not interchangeable. No microbiota-directed intervention has been tested against an HPVG endpoint and none should delay source control; probiotics, rifaximin, fecal microbiota transplantation, diet, and phage remain research questions.
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BibTeX
@article{bai2026microbiota,
title = {{Gut microbiota and innate immune barrier dysfunction in hepatic portal venous gas: a hypothesis-generating review}},
author = {Xiaoshuai Bai and Lin Zhu and Yibo Sun and Yanfei Shi and Ping Zhou and Che Wang and Lianxiang Cui and Lei Shi},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1974872},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1974872/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Gut microbiota and innate immune barrier dysfunction in hepatic portal venous gas: a hypothesis-generating review
AU - Xiaoshuai Bai
AU - Lin Zhu
AU - Yibo Sun
AU - Yanfei Shi
AU - Ping Zhou
AU - Che Wang
AU - Lianxiang Cui
AU - Lei Shi
PY - 2026
DA - 2026/10/05
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1974872
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1974872/full
AB - Hepatic portal venous gas (HPVG) is an uncommon radiographic sign whose prognosis is driven by bowel necrosis and shock rather than by intraportal gas. Immunological events along the gut–liver axis have not been synthesized for adult HPVG, and dedicated microbiome, metabolomic, gut–vascular barrier (GVB), and immune-profiling data are lacking. This hypothesis-generating review proposes gut dysbiosis as a putative contributor to mucosal and hepatic innate immune failure, inferred from cirrhosis, porto-sinusoidal vascular disease (PSVD), and intestinal ischemia/reperfusion. In those proxy states, loss of acetyl-CoA butyrate-production capacity, context-dependent bile-acid shifts, lipopolysaccharide–Toll-like receptor 4 priming, facultative-anaerobe expansion, and fermentative H ₂ /CO ₂ pathways documented in cultured HPVG isolates—Clostridium perfringens (pyruvate–ferredoxin oxidoreductase–hydrogenase) and Escherichia coli (pyruvate-formate lyase–formate hydrogen lyase)—compromise epithelial and GVB integrity. These links are not assembled as a demonstrated sequence in adult HPVG. We propose a physical-core model in which a route of entry and a local driving pressure gradient are necessary, whereas pathway-defined fermentative isolates, dysbiosis, mucosal inflammation, ischemia, and impaired portal clearance are optional amplifiers. Iatrogenic or purely pressure-related HPVG can occur without dysbiosis or a substantial pathogen-associated molecular pattern load; in necrosis-driven HPVG, dysbiosis is proposed only as a concurrent immune amplifier; when HPVG occurs in cirrhosis or PSVD, portal hypertension is treated as a host modifier of barrier geometry and washout, not as an independent generator of intraportal gas. Portal vein thrombosis, portal hypertension, pneumatosis intestinalis, pyogenic liver abscess, and HPVG may share the portal vein as a conduit but are not interchangeable. No microbiota-directed intervention has been tested against an HPVG endpoint and none should delay source control; probiotics, rifaximin, fecal microbiota transplantation, diet, and phage remain research questions.
SN - 1664-3224
ER -