Protective effects of Mycobacterium vaccae ATCC 15483 against Western diet-induced weight gain, visceral adiposity, neuroinflammation, and behavior in adolescent male mice

The prevalence of inflammatory diseases is increasing in modern urban societies, posing significant challenges to public health. Novel prevention and therapy strategies are required in order to effectively deal with this issue. One promising approach is leveraging immunoregulatory microorganisms such as Mycobacterium vaccae ATCC 15483, known for its anti-inflammatory and stress-resilience properties. This study aimed to assess whether weekly subcutaneous administrations of M. vaccae ATCC 15483 to adolescent male C57BL/6N mice can mitigate inflammation associated with Western-style diet-induced obesity, which is considered a risk factor for a number of inflammatory diseases. Our results showed that treatment with M. vaccae ATCC 15483, effectively countered Western-style diet-induced excessive weight gain, visceral adipose tissue accumulation, and elevated plasma leptin concentrations. The Western-style diet caused significant changes to the gut microbiome (e.g. lowered alpha diversity, differentiated community composition from the control diet, and an increase in the Firmicutes:Bacteroidetes ratio), which was not prevented by M. vaccae 15483, implying the seemingly protective effects of M. vaccae ATCC 15483 happen independently of the gut microbiome. Additionally, it reduced baseline levels of neuroinflammatory and microglial priming biomarkers, such as Nfkbia and Nlrp3, in the hippocampus, and notably decreased anxiety-like defensive behavioral responses. While further exploration of M. vaccae ATCC 15483 is necessary, the current study's findings provide compelling evidence supporting its potential as a promising intervention for preventing or treating adverse outcomes linked to the consumption of a Western diet, including immune-metabolic-related diseases.