New research reveals bacteria vaccination may prevent weight gain from high-fat, high-sugar diets

Exposure to a microorganism found in cow’s milk and soil may protect against Western-style diet-induced weight gain, suggests research. Vaccination with Mycobacterium vaccae bacteria in mice following a high-fat and high-sugar diet prevented excessive weight gain and reduced increases in visceral adipose tissue — fat that builds up around organs. 

The study builds on previous research indicating that the organism can prevent stress-induced inflammation and associated health problems in mice. More research is needed to determine how it prevents weight gain and if the results can be replicated in humans. 

Nutrition Insight discusses the study’s findings and implications for human health with the lead researcher, Christopher Lowry, a professor in the Department of Integrative Physiology at the University of Colorado Boulder, US. 

“There is a complex, bidirectional relationship between obesity and inflammation, in which increases in body fat can lead to chronic low-grade inflammation, which in turn can lead to further weight gain and higher risk for metabolic complications, such as metabolic syndrome and type 2 diabetes.” 

“Our studies demonstrate that regular treatment with a single species of bacterium with well-documented anti-inflammatory effects can, unexpectedly, completely prevent excessive weight gain in response to consumption of a Western-style diet.” 

Lowry says the research team hopes the study will lead to new, effective, accessible and safe approaches to preventing adverse health outcomes associated with consuming a Western-style diet. “We also hope it leads to a fundamental rethinking of what is driving the global obesity epidemic.”

Healthy vs. Western-style diets

For the study, published in Brain, Behavior and Immunity, the research team fed mice either a standard, healthy chow mix for ten weeks or a Western-style diet — containing 40.6% of calories from fat, 40.7% from carbohydrates (including 18.2% from sucrose) and 18.7% from protein. Both groups ate the same number of calories. 

Half of each group received weekly M. vaccae injections. 

At the end of the study, the mice on the Western-style diet gained significantly more weight than the healthy eaters and also had more visceral fat, which is linked to an increased risk of heart disease and diabetes. 

However, the team found no weight gain differences between the healthy eaters and the group on a Western-style diet receiving M. vaccae injections. 

University of Colorado Boulder professor Christopher Lowry in the lab (Image credit: CU Boulder).Impact of “old friends”

Lowry notes that until now, there has been limited data to suggest that single bacteria strains can prevent Western-style diet-induced weight gain. He says the study expands the scope of “old friends” benefits from stress resilience to overweight, obesity and metabolic health. 

He details that such “old friends” include certain types of microbes, such as helminthic parasites, with which humans co-evolved but have largely lost contact during urbanization. The study indicates that they can prevent weight gain induced by a Western-style diet. 

Lowry explains that these “old friends” served to regulate the immune system and suppress inappropriate inflammation. He says that as people have lost contact with these microbes, “it has put us at a higher risk for inflammatory diseases.” 

“There is something innately attractive about addressing the global obesity epidemic by simply replacing an organism that we have inadvertently lost contact with throughout our transition from hunter-gatherer to agricultural to urban lifestyles.”

Although Lowry does not advise people to intentionally get infected with parasites, he says the research may provide an alternative approach. “The bacterium we studied, M. vaccae, a prototypical ‘old friend’ found in cow’s milk and soil, was heat-killed and therefore has no risk of infection. The two ‘old friends’ types may work through similar mechanisms, driving anti-inflammatory and immunoregulatory effects.”

Preventing inflammation through immune cells

Although M. vaccae prevented weight gain, the microorganism did not affect the diversity or composition of the gut microbiome, which was altered in mice consuming a Western-style diet. The researchers speculate that the bacterium acts downstream of the microbiome to alter immunometabolic signaling. 

Lowry says: “The ability of other ‘old friends’ to prevent Western-style diet-induced weight gain is associated with upregulation of an immune cell referred to as a regulatory T cell (Treg), which prevents inappropriate inflammation. This cell is abundant in healthy adipose tissue but decreases in overweight and obesity.” 

“Low Treg levels in obesity are associated with increased risk of insulin resistance, type 2 diabetes and cardiovascular disease. Other ‘old friends’ can also shift innate immune cells, such as macrophages, to an alternatively activated state with decreased inflammation, which also may play a role.”

If successful in humans, Lowry says M. vaccae may represent a safe, effective, accessible and affordable approach to preventing obesity.He details that M. vaccae is particularly effective at increasing Treg cells, which may interrupt the cyclical relationship between obesity, chronic low-grade inflammation and inflammatory disease.

In addition to impacting immune cells, Lowry says M. vaccae also decreased markers of neuroinflammation and anxiety-like behavioral responses. 

“This was expected and is consistent with research over the last 25 years showing that M. vaccae can prevent negative outcomes of stress and promote stress resilience, preventing stress-induced inflammation, preventing stress-induced neuroinflammation, preventing priming of immune cells in the brain (i.e., microglia) and preventing stress-induced increases in anxiety and fear.”

Follow-up research

The growing prevalence of obesity and the popularity of anti-obesity medications such as GLP-1 agonists highlight an increasing commitment to address weight management with scientifically backed treatments. 

The researchers conclude that their findings provide compelling evidence supporting the potential for M. vaccae to prevent or treat adverse immunometabolic outcomes linked to consuming a Western-style diet and the associated imbalance of the gut microbiome. 

However, more research is needed, says Lowry. “Future studies can determine if the protective effects of M. vaccae against Western-style diet-induced weight gain indeed depend on its anti-inflammatory or immunoregulatory effects.” 

“We would also like to know if M. vaccae can reverse overweight or obesity once established. Finally, we’d like to know if these effects of M. vaccae can be replicated in humans.”

If successful in humans, Lowry says M. vaccae may represent a “safe, effective, accessible and affordable approach to preventing overweight and obesity, including in vulnerable populations.” 

He says the team is exploring commercial applications of this technology through a new University of Colorado Boulder spinout company, Kioga.