Consuming cholera toxin counteracts age-associated obesity

November 19, 2019

Here the research team tested a safe and well-established microbe-based immune adjuvant to restore immune homeostasis and counteract inflammation-associated obesity in animal models.

Taken together, they concluded that oral vaccination with cholera toxin B helps stimulate health-protective immune responses that counteract age-associated obesity.

Dr. Susan E. Erdman from the Division of Comparative Medicine, at the Massachusetts Institute of Technology in Cambridge, MA, United States said, "The global burden of chronic inflammatory diseases is increasing at alarming rates."

The continuous rise of obesity, cardiovascular and chronic respiratory diseases, diabetes, infertility, allergy and autoimmunity, cancer, and central nervous system dysfunctions, including anxiety and autism, appears to link with modernized lifestyle but remains inexplicable.

Figure 1: Early-life intervention with ctB rescues mice from age-associated obesity and inflammation. Shown are data collected from C57BL/6 mice of both genders at the age of 9 months. (a) At gross examination of whole body morphology, both female and male mice that consumed low doses of ctB eight months earlier have leaner physiques by comparison with untreated controls. (b) Treated mice also have less crown-like structures (CLS, arrow-heads), caused by adipocyte death-related inflammation, in their abdominal fat; (c) less myeloperoxidase-positive (MPO) granulocytes in their spleens; and (d) more anti-inflammatory Foxp3-positive regulatory T cells in their mesenteric lymph nodes compared to control mice. (e) Body weight and histomorphometrical analyses shows that the long-lasting effects of ctB are statistically significant. (a) Hematoxylin and Eosin. Scale bars: 250 μm. IHC; Diaminobenzidine chromogen, Hematoxylin counterstain. Scale bars: 25 μm. (b) Numbers on the y-axis of bar graphs correspond to the mean±SEM of the parameter assessed; *p<0.05, **p<0.01, ***p<0.001.

Underlying systemic immune imbalances linked with bacteria residing in the gut have been proposed as a probable cause of obesity.

In this context, obesity is one of many chronic inflammatory diseases associated with modern living.

Important effects of gut microbiota in mammalian physiology, including metabolism and CNS functions, place gut microbe-immune cell interactions in the hypothetical center of chronic inflammatory disorders such as obesity.

In this regard, postbiotic gut bacterial fractions used for oral immunizations have been found to stabilize the immune system and counteract destructive inflammatory responses later in life in both humans and animals.

Immune adjuvant properties of cholera-toxin, make it an attractive tool for induction of tolerance that stabilizes the immune system.

The Erdman research team concluded, "Indeed, systemic immune imbalances related to failure of tolerance have been proposed as a cause of extra-intestinal cancer linked with bacteria residing in the gut.

It remains to be seen whether this gut immune-centric strategy broadly translates to successes in the clinic; however, the versatility of ct B to manipulate immune responses make this protein a promising adjuvant for vaccine development to combat a growing Westernized public health crisis."

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