Oncotarget

Research Papers:

Consuming cholera toxin counteracts age-associated obesity

Bernard J. Varian, Theofilos Poutahidis, Gordon Haner, Alex Hardas, Vanessa Lau and Susan E. Erdman

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Oncotarget. 2019; 10:5497-5509. https://doi.org/10.18632/oncotarget.27137

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Abstract

Bernard J. Varian1, Theofilos Poutahidis1,2, Gordon Haner1, Alex Hardas2, Vanessa Lau1 and Susan E. Erdman1

1 Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, United States

2 Department of infectious Diseases and Pathology, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, 54124, Greece

Correspondence to:

Susan E. Erdman,email: [email protected]

Keywords: body weight; mouse; exotoxin subunit B; CLS; inflammation

Received: April 17, 2019     Accepted: July 05, 2019     Published: September 17, 2019

ABSTRACT

During the past forty years there has been an inexplicable increase in chronic inflammatory disorders, including obesity. One theory, the ‘hygiene hypothesis’, involves dysregulated immunity arising after too few beneficial early life microbe exposures. Indeed, earlier studies have shown that gut microbe-immune interactions contribute to smoldering inflammation, adiposity, and weight gain. Here we tested a safe and well-established microbe-based immune adjuvant to restore immune homeostasis and counteract inflammation-associated obesity in animal models. We found that consuming Vibrio cholerae exotoxin subunit B (ctB) was sufficient to inhibit age-associated obesogenic outcomes in wild type mice, including reduced crown-like structures (CLS) and granulomatous necrosis histopathology in fat depots. Administration of cholera toxin reduced weight gain irrespective of age during administration; however, exposure during youth imparted greater slenderizing effects when compared with animals receiving ctB for the first time during adulthood. Beneficial effects were transplantable to other obesity-prone animals using immune cells alone, demonstrating an immune-mediated mechanism. Taken together, we concluded that oral vaccination with cholera toxin B helps stimulate health-protective immune responses that counteract age-associated obesity.


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