Do strain diversity and/or dietary context determine the pathogenic potential of Collinsella aerofaciens in metabolic inflammation?

In recent years, interest in the role of gut microbiota alterations in the pathogenesis of non-communicable diseases (NCDs) has grown significantly. An overgrowth of Collinsella aerofaciens - a bacterium widely present in the gut ecosystem but suggested to act as a pathobiont - appears to be a common feature in individuals with NCDs and may contribute to key mechanisms such as increased intestinal permeability, low-grade inflammation and gut-liver axis dysregulation. Two non-mutually exclusive hypotheses may explain this association: 1) C. aerofaciens, which shows signatures of long-term association with the human host, can shift from a health-associated commensal to a context-activated pathobiont under industrialized-lifestyle exposures; and 2) given its high intraspecies diversity, discrete biotypes may harbor accessory genetic determinants that drive disease-associated host phenotypes. Here, we combined cell-based and ex vivo approaches to assess whether C. aerofaciens pro-inflammatory potential is primarily driven by dietary background, strain-level diversity, or both. We first characterized the C. aerofaciens type strain DSM 3979ᵀ using a Caco-2 pNiFty2-SEAP reporter model to quantify NF-κB activation and a HEK TLR2 reporter system to assess pattern-recognition receptor signaling. DSM 3979ᵀ elicited a clear TLR2-dependent response and a moderate but significant NF-κB activation. We then tested whether fecal substrates derived from short-term dietary interventions modulate C. aerofaciens fitness. Fecal samples collected from healthy volunteers after dietary phases (balanced, high-fat/low-fiber, and Western diet) were processed under anaerobic conditions and used as growth matrices for standardized inocula of DSM 3979ᵀ in batch cultures. The dietary background of the fecal substrate influenced C. aerofaciens growth, supporting the hypothesis that diet-driven changes in fecal composition can differentially support C. aerofaciens expansion. Ongoing work extends NF-κB screening to a strain panel to identify divergent host-interaction profiles. Selected high- and low-risk biotypes will then be evaluated in a murine colonization model under chow or Western-style diet to determine whether dietary context modulates C. aerofaciens-driven effects on intestinal inflammation, barrier function, and gut-liver axis-related outcomes.