Can Purified Cholera Stop Obesity?

In this 2019 study, researchers investigated the effects of purified elements of cholera toxin in age-associated weight gain.

3D illustration of the gut microbiome
3D illustration of the gut microbiome

In recent years, scientists have made significant advancements to improve our understanding of the gut microbiome. This diverse environment—of somewhere around 39 trillion microorganisms living within the digestive tracts of vertebrates (including humans, and even insects)—includes bacteria, archaea, viruses, and fungi. However, a “healthy” gut microbiota remains difficult to define in humans. The contents of the gut microbiome are not only different between women and men, microbiomes differ between… everyone. Among unrelated humans, no more than 30% of the same bacterial strains are shared in the gut microbiome. 

Different microbiomes can present with different biological reactions to outside factors, including infections and medications, and can even display different symptoms reacting to cancer and other diseases. Studies have repeatedly found that the gut microbiome plays important roles in human mood, sleep, metabolism, digestion, the immune and nervous systems, and in chronic inflammatory disorders, such as obesity.

“Indeed, earlier studies have shown that gut microbe-immune interactions contribute to smoldering inflammation, adiposity, and weight gain.”

The Hygiene Hypothesis

Researchers continue to find evidence to support the “hygiene hypothesis.” The hygiene hypothesis postulates that a lack of beneficial early-life microbe exposures can result in a dysregulated immune system later in life. This lack of early-life microbe exposures followed by immune imbalances may be responsible for the increase in obesity and other chronic inflammatory disorders over the past forty years.

“Systemic immune imbalances arising from the gut have been proposed as a probable cause of obesity [8].”

In 2019, researchers from Massachusetts Institute of Technology (MIT) and Aristotle University of Thessaloniki conducted a study to test using purified elements of the otherwise dangerous cholera toxin as a vaccination in mouse models. Their theory was that this safe and well-established cholera-based immune adjuvant would cause an immune system reaction that reduces the inflammation associated with age-related obesity. Their research paper was published by Oncotarget and entitled, “Consuming cholera toxin counteracts age-associated obesity.” (Go Behind the Study to learn why the researchers decided to use the cholera toxin.)

The Study

First, the researchers used both inbred and outbred mouse models to test the effects of the cholera-toxin subunit B (ctB)—a component of the Dukoral® vaccine used in humans for cholera diarrhea prevention. For each mouse model tested in the study, four different groups of eight mice each were examined: a female control group, a vaccinated female group, a male control group, and a vaccinated male group. At four weeks of age, the study mice were given three doses every-other-week of ctB at 10 micrograms. The control mice were given sham doses. The researchers found that in ctB vaccinated mice, the oral vaccination prevented age-associated weight gain compared to the control mice in both models.

Next, the researchers used an obese mouse model to test the effects of ctB dosing in early-life and to test the effects of transfering their gut flora into another mouse. The researchers found that the obese-mouse microbiome was sufficient to trigger obesity and inflammation in other mice when compared to sham-dosed control mice. In the obese mouse model, ctB dosing in early life also inhibited age-associated weight gain. This probiotic inhibited weight gain in mice dosed in early-life, and also in mice dosed in adulthood.

“Although we discovered dramatic benefit after early-life exposures to ctB, mice were also significantly slimmer when dosed with ctB for the first time during adulthood at 12-wks-of-age or 24-wks-of-age.”

Conclusion

The researchers found that purified elements of the cholera toxin stabilized immunity, through the gut microbiome, and inhibited age-associated obesity in multiple mouse models. Further studies are necessary to determine the degree to which an early-life microbe exposure such as this impacts immunity versus first-time adulthood exposures. Humans have been taking pre- and probiotics for quite some time without a strong grasp of exactly how these microbe infusions work. This research contributed to a better understanding of how humans can modulate our own gut microbiome to improve many aspects of our health and well-being.

“This type of microbe-immune re-programming may ultimately target other diseases linked with obesity and inflammation such as diabetes [19], multiple sclerosis [64], and cancer [25].”

Click here to read the full research paper, published by Oncotarget.

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