A 6-week randomized trial reported that a daily kefir-based synbiotic—containing 27 bacterial cultures combined with a multifiber, 18-component prebiotic blend—lowered several inflammation-related proteins more broadly than either inulin or omega-3 supplementation evaluated in a separate randomized trial of older adults.
In the synbiotic group, significant declines were observed in interleukin-6 (IL-6), interferon-γ (IFN-γ), SIRT2, 4EBP1, CCL23, CCL25, and CCL28, though the largest effect sizes were observed for SIRT2, 4EBP1, and CCL23 after false-discovery-rate adjustment. For context, effect sizes (Cohen’s d) were: IL-6 d = −0.882, SIRT2 d = −1.505, 4EBP1 d = −1.384, and CCL23 d = −1.356.
In contrast, omega-3 and inulin produced narrower biomarker changes, and both were associated with reductions in TNF-α relative to controls after multiplicity correction. Across interventions, Dr. Amrita Vijay, of the University of Nottingham in the UK, and colleagues quantified 92 inflammation-related proteins using the Olink Target 96 inflammation panel based on proximity extension assay. FDR-adjusted P < .05 was considered statistically significant overall; for volcano-plot visualization and key between-group signals, an FDR threshold of P < .003 (−log P = 2) was applied, which the principal synbiotic-associated proteins met.
In the synbiotic arm, serum butyrate increased over 6 weeks, and higher butyrate levels correlated inversely with IL-6 at the end of the intervention (r = −0.57; P = .01). No significant correlations were observed between butyrate and the other inflammatory proteins, despite increases in all measured short-chain fatty acids with the synbiotic, suggesting alternative mechanistic pathways yet to be clarified. Total cholesterol, LDL cholesterol, and non-HDL cholesterol decreased with the synbiotic, while glucose, insulin, and HOMA-IR did not change significantly during the study period.
The work comprised two randomized interventions: a synbiotic vs no-supplement control in generally healthy adults (n = 20 vs n = 20; registered as NCT06480812), and participants randomized 1:1 to omega-3 vs inulin in a 2-arm trial of older adults (omega-3 n = 33; inulin n = 31; registered previously as NCT03442348). Because the omega-3/inulin cohort was older than the synbiotic/control cohort, between-group comparisons involving those arms were adjusted for age. The synbiotic’s prebiotic blend included a broad array of fermentable fibers—such as inulin, galacto-oligosaccharides, fructo-oligosaccharides, resistant starch, arabinoxylan, beta-glucans, pectin, and xylo-oligosaccharides, among others—designed to stimulate diverse microbial pathways. The omega-3 dose was 500 mg/day and provided approximately 165 mg EPA and 110 mg DHA. The inulin dose was 20 g/day. Only the synbiotic trial included a contemporaneous no-supplement control; comparisons for omega-3 and inulin used the synbiotic study’s control group, which contributed to the noted age mismatch. Participants were asked to maintain their usual diet and activity during the intervention.
The authors interpreted the synbiotic’s effects as consistent with gut–immune interactions in which microbial fermentation products such as butyrate may down-regulate proinflammatory signaling. They also highlighted the functional relevance of several targets: SIRT2 has been proposed as a therapeutic target in viral infections (including hepatitis B), and studies have shown that modulating SIRT2 activity can influence viral transcription and replication.
Important limitations include small sample sizes, lack of blinding and absence of a true placebo, and age mismatch between the two trials, which was addressed statistically but nonetheless constrains generalizability. The investigators did not perform microbiome profiling, which limits mechanistic inference and underscores the need for placebo-controlled studies with metagenomics and longer follow-up to determine whether the observed molecular changes translate into sustained improvements in inflammation and cardiometabolic health.
The synbiotic trial was funded by Chuckling Goat Ltd. The omega-3 and inulin studies were supported by the Chronic Disease Research Fund. Investigators reported advisory roles and consulting relationships.