Gut lymph hypothesis of early shock and trauma-induced multiple organ dysfunction syndrome: a new look at gut origin sepsis
Abstract
Trauma is the leading cause of death in people aged < 40 years and multiple organ dysfunction syndrome (MODS) is the leading cause of death in intensive care units. Consequently, understanding the mechanisms by which trauma/hemorrhagic shock (T/HS) leads to acute (non-infectious) MODS is of major health importance in the USA. One of the major hypotheses being studied to explain the development of sepsis and MODS after trauma is the gut hypothesis of MODS. Additionally, there is recent experimental and clinical information that the response to injury and sepsis may differ between males and females. Thus, the overall global hypothesis of this review is that T/HS-induced early distant organ injury and cellular dysfunction is secondary to gut injury and is primarily mediated by factors exiting the gut via the mesenteric lymphatics. A secondary major hypothesis which will be presented is that gender and sex hormones modulate gut and hence distant organ and cellular dysfunction after T/HS. These hypotheses are supported by our studies indicating that T/HS-induced lung injury and endothelial cell activation/dysfunction, neutrophil activation, red blood cell dysfunction and bone marrow failure in male rats are mediated primarily by factors exiting the gut in the mesenteric lymph. Additionally, our studies show that proestrus female rats are resistant to these T/HS-induced injuries. Based on these results supporting the gut lymph hypothesis of systemic inflammatory response syndrome and MODS, and studies showing that female rats are more resistant to T/HS than male rats, the effects of gut-derived factors in lymph, as well as the effects of gender and sex hormones on cellular and organ dysfunction after T/HS, appear to be fruitful areas for further investigation.
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In clinical studies of critically ill high-risk surgical patients and in animal studies of shock, bacteria have been cultured from the mesenteric lymph nodes.
“In clinical studies of critically ill high-risk surgical patients and in animal studies of shock, bacteria have been cultured from the mesenteric lymph nodes.”
From The microbiome and critical illness (2016) · cites this paper as [102]
Substantial clinical and experimental evidence supports the gut-lymph hypothesis.
“Substantial clinical and experimental evidence supports the gut-lymph hypothesis.”
From The microbiome and critical illness (2016) · cites this paper as [102]
In animal studies of shock, ligation of the mesenteric duct protected against lung injury.
“In animal studies of shock, ligation of the mesenteric duct protected against lung injury”
From The microbiome and critical illness (2016) · cites this paper as [102]
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Tulli, G., & Zuanetti, G. (2022) · Springer eBooks · doi:10.1007/978-3-031-14612-1_7
Kryukov, E. V., Ivchenko, E. V., Vb, G., Першко, А. М., Ефимов, И. В., & Sorokin, A. N. (2026) · Bulletin of the Russian Military Medical Academy · doi:10.17816/brmma676910
- Authors
- Deitch, E. A., Xu, D.-Z., & Lu, Q.
- Affiliations
- Rutgers New Jersey Medical School (US)
- Corresponding author
- Deitch, Edwin A.
- ORCID
- Venue
- Journal of Organ Dysfunction
- Publisher
- Informa UK Limited
- Published
- 2006-01
- Volume
- 2
- Issue
- 2
- Pages
- 70-79
- ISSN
- 1747-1060 (ISSN-L)
- 1747-1079
- OpenAlex
- W2045208670
- Cited by
- 35
- References
- 57
- Citations by year
- 2026: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2018: 2 · 2017: 2 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 3
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Organ Dysfunction (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Trauma, Hemostasis, Coagulopathy, Resuscitation
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Keywords
- multiple organ failure, sepsis, mesenteric lymphatics, intestinal injury, sex hormones, sex differences, systemic inflammatory response syndrome, lung injury, endothelial dysfunction, neutrophil activation, bone marrow failure
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