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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237453PMC
http://dx.doi.org/10.1172/jci.insight.121045DOI Listing

Publication Analysis

Top Keywords

lymph node
16
cardiac allografts
8
inflammation fibrosis
8
colitic fmt
8
node structure
8
laminin α4/α5
8
α4/α5 ratio
8
fmt
5
pseudolongum
5
gut microbiota-dependent
4

Similar Publications

Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer.

N Engl J Med

January 2025

From Bielefeld University, Medical School and University Medical Center Ostwestfalen-Lippe, Campus Hospital Lippe, Detmold, Germany (J.H.); the Department of Radiation Oncology, Medical University of Graz, Graz, Austria (T.B.); the Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany (C.S.); the Institute of Surgical Pathology, University Medical Center Freiburg, Germany (P.B.); the Department of Surgery, University Medical Center Schleswig-Holstein-Campus Lübeck, Lübeck, Germany (B.K., T.K.); Comprehensive Cancer Center Augsburg, Faculty of Medicine, University of Augsburg, Augsburg, Germany (R.C.); the Department of General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany (S.U.); the Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (J.R.I.); the Department of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute and San Raffaele Vita-Salute University, Milan (I.G.); the Department of General, Visceral, Thoracic, and Endocrine Surgery, Johannes Wesling University Hospital Minden, Ruhr University Bochum, Minden, Germany (B.G.); the Department of General, Visceral, and Pediatric Surgery, University Medical Center Göttingen, Göttingen, Germany (M.G.); the Department of General, Visceral, Thoracic, Transplantation, and Pediatric Surgery, University Medical Center Schleswig-Holstein-Campus Kiel, Kiel, Germany (B.R.); the Department of General, Visceral, Transplantation, Vascular, and Pediatric Surgery, University Hospital, University of Würzburg, Würzburg, Germany (J.F.L.); the Department of General, Visceral, Cancer, and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany (C.B.); the Department of Hematology and Oncology, Sana Klinikum Offenbach, Offenbach am Main, Germany (E.R.); the Department of Surgery, Klinikum Dortmund, Klinikum der Universität Witten-Herdecke, Dortmund, Germany (M.S.); the Department of Surgery, University Hospital Magdeburg, Magdeburg, Germany (F.B.); the Department of Medicine I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany (G.F.); the Department of Hematology, Oncology, and Cancer Immunology, Charité-University Medicine Berlin, Campus Virchow-Klinikum, Berlin (P.T.-P.); the Department of General, Visceral, Cancer, and Transplantation Surgery, University Hospital Essen, Essen, Germany (U.P.N.); the Department of General, Visceral, and Transplantation Surgery, University Hospital Muenster, Muenster, Germany (A.P.); the Department of Radiotherapy and Oncology, Goethe University Frankfurt, University Hospital, Frankfurt, Germany (D.I.); the Division of Gastroenterology, Rheumatology, and Infectology, Department of Medicine, Charité-Universitätsmedizin Berlin, Berlin (S.D.); the Department of Surgery, Robert Bosch Hospital, Stuttgart, Germany (T.S.); the Department of Surgery, University Medical Center Erlangen, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany (C.K.); the Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany (S.Z.); the Department of General, Visceral, and Transplant Surgery, Ludwig Maximilian University Hospital, Munich, Germany (J.W.); the Department of Internal Medicine I, Klinikum Mutterhaus der Borromaerinnen, Trier, Germany (R.M.); the Departments of Hematology, Oncology, and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany (G.I.); the Department of General, Visceral, and Transplant Surgery, University Medical Center Mainz, Mainz, Germany (P.G.); and the Department of Medicine II, University Cancer Center Leipzig, Cancer Center Central Germany, University Medical Center Leipzig, Leipzig, Germany (F.L.).

Background: The best multimodal approach for resectable locally advanced esophageal adenocarcinoma is unclear. An important question is whether perioperative chemotherapy is preferable to preoperative chemoradiotherapy.

Methods: In this phase 3, multicenter, randomized trial, we assigned in a 1:1 ratio patients with resectable esophageal adenocarcinoma to receive perioperative chemotherapy with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) plus surgery or preoperative chemoradiotherapy (radiotherapy at a dose of 41.

View Article and Find Full Text PDF

Background: Francisella tularensis is an aerobic, gram negative coccobacillus bacterium that causes tularemia. F. tularensis spreads primarily through ticks, biting flies, droplet inhalation, contaminated mud or water, or infected animal bites, and it can survive in animal carcasses with the most common mode of transmission occurring via inoculation into the skin and inhalation/ingestion.

View Article and Find Full Text PDF

Background: C-type lectin (CTL) plays an important act in parasite adhesion, host's cell invasion and immune escape. Our previous studies showed that recombinant Trichinella spiralis C-type lectin (rTsCTL) mediated larval invasion of enteral mucosal epithelium. The aim of this study was to investigate protective immunity produced by vaccination with rTsCTL and its effect on gut epithelial barrier function in a mouse model.

View Article and Find Full Text PDF

Objective: The prevalence of Thyroid-Cancer (TC) has increased worldwide and an association with metabolic and cardio-vascular disorders has been reported. Moreover, an increasing percentage of patients are currently diagnosed incidentally through non-thyroid related imaging for other clinical conditions. Our aim was to assess the prevalence of Thyroid-Related (TD) versus Incidental (ID) pre-surgery reasons leading to TC diagnosis and to compare the two groups in terms of clinical characteristics, size and severity of TC at presentation and rate of non-thyroid cancers and cardiovascular/metabolic comorbidities.

View Article and Find Full Text PDF

Previous studies have reported that chronic lymphocytic leukemia (CLL) shows a de novo chromatin activation pattern as compared to normal B cells. Here, we explored whether the level of chromatin activation is related to the clinical behavior of CLL. We identified that in some regulatory regions, increased de novo chromatin activation is linked to clinical progression whereas, in other regions, it is associated with an indolent course.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!