To answer those, we compared two fermentable fibres — acacia gum (AG; n=75) and resistant starch type 4 (RS4; n=75) — with a non-fermentable control (MCC; n=45) in adults with excess body weight, integrating clinical outcomes with microbiome, metabolomic, and genomic profiling.
AG and RS4 induced clear, structure-specific shifts in microbiome composition (incl. distinct Bifidobacterium spp.) and SCFAs. But these “prebiotic-like” changes did not explain most physiological outcomes.
LBP, calprotectin, TNF-α, IL-6, and satiety improved across several groups — including MCC — with no detectable microbiome associations, indicating fermentation-independent mechanisms.
Benefits are target-specific, arise through microbiome-independent and microbiome-dependent mechanisms, and individualized effects can, in some cases, be predicted from microbiome features. Overall, this supports a more targed and personalized application of fibre supplements.
Some outcomes were microbiome-linked: • AG ↓ ghrelin, linked to shifts in microbial CAZyme genes targeting AG’s specific glycan structures. • ML models predicted BP improvements with AG and CRP reductions with RS4 from microbial pathways and faecal bile acids.