Bridging the gap between healthspan and lifespan requires targeted dietary strategies that modulate inflammation, a key driver of age-related decline(1). The gut microbiome plays a central role in this process, influencing immune function and metabolic health(2). We investigated the impact of a six-week dietary intervention with prebiotics, omega-3, and synbiotics (fermented kefir + prebiotic fibre mix) on systemic inflammation, aiming to uncover mechanisms that may support healthy ageing through diet-microbiome-immune interactions.

Proteomic profiling using the Olink 96 inflammation target panel was performed on fasting serum samples collected at baseline and follow-up of a 6-week intervention with a highly fermented kefir plus a prebiotic fibre mix (n=20) (170ml of kefir combined with 10g of prebiotic fibre mix), 500 mg of omega-3/day, 20g inulin/day or nothing. Changes from baseline and differences in change compared to the control group were analysed using standard parametric methods. Cohen’s delta was computed as a measure of effect size. An FDR p<0.05 was considered as statistically significant.

All three interventions resulted in significant drops in systemic inflammation markers compared to controls.TNF-α decreased by Δ -0.303 (SD 0.718); Cohen’s d -0.618 in the omega-3 arm and by Δ -0.402 [SD 0.449]; Cohen’s d -1.012 in the inulin arm, while IFN-γ Δ -0.597 [SD 0.428]; Cohen’s d=-0.940 and IL-6 Δ -0.479 [SD 0.338]; Cohen’s d=-0.882 decreased in the synbiotic arm. The strongest drops were observed in other markers, notably SIRT2 (Δ -0.636 [SD 0.482] d=-1.505 p<0.0001), 4EBP1 (Δ -0.875 [SD 0.634]; d=- 1.384 p=0.0004), CCL23 (Δ -0.812 [SD 0.919]; d=-1.356 p=0.0002) following synbiotic supplementation, along with changes in two mucosal cytokines (CCL25 Δ -0.566 [SD 0.659]; d=-1.137 p=0.001) and CCL28 (Δ -0.477 [SD 0.591]; d=-1.006 p=0.003). We also saw significant increases in short-chain fatty acids, specifically butyrate, which correlated with the decrease in levels of IL-6 following synbiotic supplementation.

Synbiotic supplementation led to the most significant changes across inflammatory markers, particularly those linked to metabolic and immune function. These findings highlight the potential of targeted dietary interventions to modulate host–microbiome interactions and inflammation, offering a promising strategy to support healthy ageing and extend healthspan.