Gut microbiota-dependent modulation of innate immunity and lymph node remodeling affects cardiac allograft outcomes
Open accessAbstract
We hypothesized that the gut microbiota influences survival of murine cardiac allografts through modulation of immunity. Antibiotic pretreated mice received vascularized cardiac allografts and fecal microbiota transfer (FMT), along with tacrolimus immunosuppression. FMT source samples were from normal, pregnant (immune suppressed), or spontaneously colitic (inflammation) mice. Bifidobacterium pseudolongum ( B. pseudolongum ) in pregnant FMT recipients was associated with prolonged allograft survival and lower inflammation and fibrosis, while normal or colitic FMT resulted in inferior survival and worse histology. Transfer of B . pseudolongum alone resulted in reduced inflammation and fibrosis. Stimulation of DC and macrophage lines with B . pseudolongum induced the antiinflammatory cytokine IL-10 and homeostatic chemokine CCL19 but induced lesser amounts of the proinflammatory cytokines TNFα and IL-6. In contrast, LPS and Desulfovibrio desulfuricans ( D. desulfuricans ), more abundant in colitic FMT, induced a more inflammatory cytokine response. Analysis of mesenteric and peripheral lymph node structure showed that B . pseudolongum gavage resulted in a higher laminin α4/α5 ratio in the lymph node cortical ridge, indicative of a suppressive environment, while D . desulfuricans resulted in a lower laminin α4/α5 ratio, supportive of inflammation. Discrete gut bacterial species alter immunity and may predict graft outcomes through stimulation of myeloid cells and shifts in lymph node structure and permissiveness.
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Molecules produced by microbiota, such as LPS, can induce cytokine production and lead to depressive symptoms.
“Molecules produced by microbiota, e.g. LPS, can induce cytokine production (198), and lead to depressive symptoms (199).”
From Cytokine Research in Depression: Principles, Challenges, and Open Questions (2019) · cites this paper as [198]
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References 98 · Cited by 73
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- Authors
- Bromberg, J. S., Hittle, L., Xiong, Y., Saxena, V., Smyth, E. M., Li, L., Zhang, T., Wagner, C., Fricke, W. F., Simon, T., Brinkman, C. C., & Mongodin, E. F.
- Affiliations
- University of Maryland, Baltimore (US)
- University of Hohenheim (DE)
- Centre National de la Recherche Scientifique (FR)
- ORCID
- Venue
- JCI Insight
- Published
- 2018-10-04
- Volume
- 3
- Issue
- 19
- ISSN
- 2379-3708 (ISSN-L)
- PMC
- PMC6237453
- OpenAlex
- W2895435337
- Cited by
- 73
- References
- 98
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 7 · 2023: 13 · 2022: 8 · 2021: 13 · 2020: 10 · 2019: 11
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- JCI Insight (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- This work was supported by a grant from the Living Legacy Foundation of Maryland (Living Legacy Foundation of Maryland)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Health Sciences › Medicine › Transplantation › Organ and Tissue Transplantation Research
- Keywords
- gut microbiota, cardiac allograft survival, fecal microbiota transplantation, Bifidobacterium pseudolongum, Desulfovibrio desulfuricans, innate immunity, allograft inflammation, myocardial fibrosis, IL-10, CCL19, myeloid cells, tacrolimus immunosuppression, colitis, pregnancy
- MeSH terms
- RAW 264.7 Cells, Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Animals, Anti-Bacterial Agents, Colitis, Disease Models, Animal, Female, Graft Rejection, Graft Survival, Humans, Immunity, Innate, Immunosuppressive Agents, Lymph Nodes, Myocardium, Pregnancy, Heart Transplantation, Cytokines, Tacrolimus, Treatment Outcome, Cell Line, Tumor, Mice, Allografts
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