Gut microbiome-derived metabolic remodeling and the butyrate–IL-18 inflammatory axis after transcatheter aortic valve implantation
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Background
Severe aortic stenosis is associated with systemic and splanchnic hemodynamic disturbances that may alter gut microbial metabolism and host inflammatory responses.
Objectives
We aimed to determine whether TAVI remodels the gut microbiome-derived metabolome and whether post-procedural SCFA dynamics are associated with the inflammatory cytokine response.
Methods
We conducted a prospective paired single-center study of patients undergoing elective TAVI at Bern University Hospital. Stool and blood samples were collected before and three months after the procedure. Gut microbial composition was profiled by full-length 16S rRNA sequencing, circulating short-chain fatty acids (SCFAs) by targeted metabolomics, and inflammatory mediators by multiplex cytokine analysis, and integrated with hemodynamic and clinical data.
Results
Forty patients were enrolled. Following TAVI, microbial richness declined without significant restructuring of overall community composition. In contrast, circulating SCFA profiles were significantly remodeled, driven by selective reductions in butyrate and isovalerate. A greater decline in circulating butyrate was inversely associated with IL-18 elevation (ρ⍰=⍰−0.668, p⍰<⍰0.001, n⍰=⍰36), independent of aortic valve calcification burden, hemodynamic improvement, and cardiovascular medications. Baseline isovalerate was nominally associated with 1-month adjudicated adverse events (AUC⍰0.77; exploratory).
Conclusions
TAVI is associated with selective changes in gut microbiome-derived metabolic output rather than broad alterations in microbial community structure. Declining circulating butyrate identifies a gut–metabolite–immune axis linked to IL-18 dynamics and represents a potential biomarker of inflammatory recovery following valve intervention.
Condensed Abstract
Whether TAVI remodels the gut microbiome-derived metabolome and whether short-chain fatty acid (SCFA) dynamics couple to the post-procedural inflammatory response has not been examined. In 40 patients undergoing elective TAVI, paired stool and serum samples collected before and three months after the procedure were analyzed by full-length 16S rRNA sequencing, targeted SCFA metabolomics, and multiplex cytokine profiling. Gut microbial richness declined modestly without significant restructuring of community composition. Circulating butyrate and isovalerate were selectively reduced after TAVI. Post-procedural butyrate decline was specifically and inversely associated with IL-18 elevation (ρ⍰=⍰−0.668, p⍰<⍰0.001), independent of hemodynamic response, calcification burden, and cardiovascular risk profile. These findings identify a gut-metabolite-immune axis that may represent a modifiable biological dimension of post-procedural recovery after cardiac valve intervention.
