Preventing Obesity With Gut Bacteria

These specific gut bacteria prevent mice from becoming obese – what could that mean for us?

A specific class of bacteria from the gut has been identified by researchers at the University of Utah Health – that literally prevents mice from becoming obese in studies. There is a strong potential that these very same microbes may also control weight in humans. Clostridia (most species of the genus Clostridium are saprophytic organisms found in many places in the environment, most notably the soil), a beneficial bacteria identified in the microbiome (a collective of trillions of microorganisms & bacteria that inhabit the gut and intestines).

The study which was published 25th July online in the Journal Science shows that healthy mice have plenty of Clostridia (which is a class of around 20 to 30 bacteria). However, mice with an impaired immune system (in this study immune-compromised mice with a lack of IgA production in the gut had reduced numbers of Clostridia bacteria in their microbiomes) appear to lose these specific microbes from their gut as they ago.

Interesting and critical to note that the mice with a reduced concentration of Clostridia inevitably become obese despite being fed a healthy diet. During the research, when this specific class of microbes was introduced back into the diet, these mice were able to stay slim, avoiding obesity.

June Round, Ph.D., an associate professor of pathology at U of U Health, is the study’s co-senior author along with U of U Health research assistant professor W. Zac Stephens, Ph.D. Charisse Petersen, Ph.D., a graduate student at the time, led the research.

“Now that we’ve found the minimal bacteria responsible for this slimming effect, we have the potential to really understand what the organisms are doing and whether they have therapeutic value,” Round says.

Microbiome Species that Keep Mice Lean or Obese Are Balanced by Immune System

It is estimated that more than 1.9 billion people around the world are now obese and due to obesity, are at a very real risk of developing metabolic disorders such as type 2 diabetes, cardiovascular or liver disease. Multiple research studies have focused on the important role of the immune system in metabolic disease, and in particular on inflammatory responses in obesity.

This particular research shows us how specialised immune cells can actually protect against obesity and associated metabolic syndrome by controlling communities of intestinal bacteria that either promote or reduce fat absorption.

Results from this study found that Clostridia literally prevents weight gain by blocking the intestine’s ability to absorb fat.

The mice that were experimentally treated so that Clostridia were the only bacteria living in their gut were shown to be leaner with less fat, than mice that had no microbiome at all. They also had lower levels of a gene, CD36, that regulates the body’s uptake of fatty acids. CD36 is basically a molecule that literally prevents the gut from absorbing fat.

Based on this understanding, the next step would be to isolate these specific molecules to determine how they work in humans; research that could lead to a new form of therapeutic approach to treating obesity, diabetes and other such metabolic disorders.

“These bacteria have evolved to live with us and benefit us,” Petersen says. “We have a lot to learn from them.“

The significant research study actually almost didn’t happen. In many ways, it was a breadcrumb trail that led Petersen down this path of study. Originally, the link to compromised immune system and obesity came about when the researcher noticed that genetically engineered mice that lacked the myd88 gene (central to the immune response) were quite literally “as fat as pancakes”. By allowing the rodents to age longer than usual, the surprising an unappreciated link between immunity and obesity became entirely apparent. This single observation though didn’t fully reveal why the mice became overweight specifically – only highlighting the significance.

Thankfully, due to previous historical research carried out in the Round Lab, Peterson did suspect that the microbiome was most likely involved in the process. It had been previously noted in research that by impairing the body defences, certain bacterial strains are able to dominate over others. This shift in gut bacteria can negatively impact health. So the link between a healthy immune system and a healthy balance of diverse bacteria in the gut was a naturally progressive thought process.

Subsequently it was determined and observed that the obesity in immune-compromised mice, stemmed from the failure of the body’s defensive system to appropriately recognise bacteria. These mice produced fewer of the antibodies that ordinarily latch onto the microbiome like target-seeking missiles. This change made the gut less hospitable for Clostridia, leading to more fat absorption and excessive weight gain. Simultaneously, as Clostridia reduced, researchers noticed increased numbers of a bacterium called Desulfovibrio. This organism has previously been linked with inflammatory bowel disease and type 2 diabetes and obesity, the authors pointed out. The experiments indicated that the Desulfovibrio species flourished in the immune-compromised animals, at the expense of the Clostridia species. Over time, the mice also developed signs of type 2 diabetes, as well as obesity.

Interestingly, human studies suggest that obese individuals have lower mucosal immunoglobulin A (IgA) levels, suggesting that they can’t mount an effective immune response.

Similarly in humans and previous research, it has been found that people who are obese also lack Clostridia. This clearly mirrors the same situation with the mice. It should also be noted that there are indications that humans suffering from obesity or are type 2 diabetics, likewise have a suboptimal immune response.

Conclusion and Further Research

It is the ambition of this further research to understand the connections and insights into preventing & treating these metabolic health conditions through understanding the gut microbiome more fully.

“We’ve stumbled onto a relatively unexplored aspect of type 2 diabetes and obesity,” Round says. “This work will open new investigations on how the immune response regulates the microbiome and metabolic disease.“

“Now that we’ve found the minimal bacteria responsible for this slimming effect, we have the potential to really understand what the organisms are doing and whether they have therapeutic value,” suggested June Round, PhD

More information: C. Petersen el al., “T cell–mediated regulation of the microbiota protects against obesity,” Science (2019).