Gut Microbiome Depletion Decreases Tumor Burden through an Immune Mediated Mechanism
Abstract
Objective: Bacterial cells residing in our gut significantly outnumber our own cells to form a distinct ‘metagenome’. This so-called ‘hidden organ’ can be modified with diet, drugs or disease states. While the role of... [ view full abstract ]
Objective: Bacterial cells residing in our gut significantly outnumber our own cells to form a distinct ‘metagenome’. This so-called ‘hidden organ’ can be modified with diet, drugs or disease states. While the role of gut microbiome in the etiopathology of allergies, inflammatory bowel disease, obesity etc. has been well studied; little is known on how gut microbiome effects cancer or vice-versa. We aimed to evaluate this cancer-gut microbiome axis. Methods: Age- and sex-matched C57BL/6J mice were either orally given saline (Saline group) or a cocktail of gut-sterilizing poorly-absorbable broad spectrum antibiotics (Abx group). After 2 weeks of treatment, Abx and Saline mice were implanted subcutaneously with BRAF/PTEN melanoma cells or KPC pancreatic cancer cell line or given liver metastasis through an intrasplenic injection of B16-F10 melanoma cells. To elucidate the role of immunity, similar experiments were repeated in mice with Rag1tm1Mom mutation (RAG1 KO mice) which have a non-functional adaptive immune system. Results: In all three cancer models, tumors were significantly smaller in Abx mice vs saline mice . Tumors from Abx mice also showed significantly lower Ki-67 immunofluorescence and splenocytes from these mice showed higher anti-cancer cytotoxicity. However, ability of gut microbiome depletion to reduce cancer growth was lost in RAG1 KO mice suggesting an immune-mediated mechanism. Flowcytometry revealed that a significantly higher percentage of NKT cells and macrophages in Abx treated tumors were secreting TNF (an important tumor suppressing cytokine and a marker of M1 phenotype).Conclusion: Gut sterilization decreases cancer burden through a possible immune-mediated mechanism.
Authors
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Vrishketan Sethi
(University of Miami – Miller School of Medicine, Miami, Florida, USA)
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Bhuwan Giri
(University of Miami – Miller School of Medicine, Miami, Florida, USA)
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Bharti Garg
(University of Miami – Miller School of Medicine, Miami, Florida, USA)
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Shrey Modi
(University of Miami)
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Rajinder Dawra
(University of Miami)
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Sulagna Banerjee
(University of Miami)
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Sabita Roy
(University of Miami)
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Sundaram Ramakrishnan
(University of Miami – Miller School of Medicine, Miami, Florida, USA)
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Ashok Saluja
(University of Miami – Miller School of Medicine, Miami, Florida, USA)
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Vikas Dudeja
(University of Miami Leonard M. Miller School of Medicine, Miami, Florida, U.S.A.)
Topic Areas
Colorectal Surgery , Surgical Oncology
Session
Plenary » Plenary Scientific Session (10:25 - Friday, 22nd September, Bradley Lecture Center)