M. intestinale induces a pro-inflammatory response in glioma bearing mice, inhibiting tumor growth via TLR2-dependent signaling.
Key Findings
Results
Glioma growth in mice is inversely correlated with the relative abundance of Muribaculum intestinale in feces.
Relative abundance of M. intestinale was measured in fecal samples from glioma-bearing mice
The inverse correlation was identified through analysis of gut microbiota composition during glioma progression
This finding motivated subsequent experimental investigation of M. intestinale administration
Results
M. intestinale administration reduced glioma growth in mice.
Tumor size or volume was measured following oral administration of M. intestinale to glioma-bearing mice
Reduction in glioma growth was observed compared to control groups not receiving M. intestinale
This anti-tumor effect was one of four major outcomes attributed to M. intestinale administration
Results
M. intestinale administration induced an inflammatory environment in the gut.
Gut inflammation was assessed following M. intestinale administration in glioma-bearing mice
This pro-inflammatory gut response was identified as one of the primary effects of M. intestinale treatment
The inflammatory environment in the gut was associated with downstream systemic and intratumoral immune changes
Results
M. intestinale administration increased the pro-inflammatory profile of tumor-associated microglial cells and the frequency of CD8+ T cells in glioma-bearing mice.
Tumor-associated microglial cells exhibited an increased pro-inflammatory profile following M. intestinale treatment
CD8+ T cell frequency was elevated in mice administered M. intestinale compared to controls
These intratumoral immune changes were consistent with an anti-tumor immune response
Results
M. intestinale administration increased peripheral TNF-α levels in glioma-bearing mice.
Peripheral TNF-α was measured as a marker of systemic inflammatory response
Elevated TNF-α levels were observed following M. intestinale administration
This systemic cytokine elevation was one of four major effects attributed to M. intestinale treatment
Results
The effects induced by M. intestinale administration were significantly attenuated upon TLR2 silencing using TLR2-targeting siRNA.
TLR2 was silenced using TLR2-targeting siRNA in glioma-bearing mice treated with M. intestinale
Attenuation of effects included reduction in the anti-tumor and pro-inflammatory responses induced by M. intestinale
TLR2, as a pattern-recognition receptor, detects microbial-associated molecular patterns and orchestrates host immune responses to infection
These results establish TLR2-dependent signaling as the mechanistic pathway through which M. intestinale exerts its effects