Megasphaera in the gut microbiome and cancer: from Megasphaera elsdenii dysbiosis to Megasphaera sp. XA511 in tumor microenvironments

Growing evidence suggests that the gut microbiome and specific gut microbes influence carcinogenesis both within the gastrointestinal tract and in distant organs through immune, metabolic, and inflammatory pathways. Megasphaera elsdenii, a gram−negative-staining, strictly anaerobic member of the Veillonellaceae family, has been implicated in disruption of colonic epithelial homeostasis and may exert systemic effects beyond the intestine. While much attention has focused on the gut–brain axis, this mini−review synthesizes current evidence linking intestinal dysbiosis, microbial metabolite signaling, and immune crosstalk along the gut–lung axis. By integrating findings from studies on microbial translocation, mucosal immunity, and metabolite−mediated inflammation, we present a hypothesis−generating model in which M. elsdenii–driven gut dysbiosis may shape lung cancer pathogenesis through short−chain fatty acid–dependent immunometabolic signaling and hypothesized lymphatic and outer membrane vesicle–mediated pathways, recognizing that existing lung data derive solely from non−causal, genus−level 16S rRNA surveys. We further distinguish viable colonization from detection of immunogenic DNA and vesicular debris in distal tissues and discuss the context−dependent roles of the genus, contrasting the systemic pathogenicity of M. elsdenii in the gut–lung axis with the divergent, protective metabolic profile of a distinct gut−derived strain, Megasphaera sp. XA511, in pancreatic tumor microenvironments. This framework highlights Megasphaera as an understudied but potentially actionable modulator of cancer immunobiology.