Novel formulated food for the elderly regulates specific gut bacterial taxa and improves host physiology

Evidence has demonstrated established associations and causal links between gut microbiota and host aging, with microbiota-targeted dietary interventions potentially mitigating age-related decline. In addition, current formulations considering comprehensive and balanced nutritional needs of the elderly are very few. Therefore, we developed a Novel Formulated Food for the Elderly (NFFE) that is enriched with prebiotics (fructooligosaccharide (FOS) and edible fungal β-glucans) targeting gut microbiota and addresses complete and specific nutritional requirements of the elderly. After an 8-week intervention in a randomized self-controlled trial, age-related physiological decline in participants was significantly mitigated. Notably, NFFE selectively enriched short-chain fatty acid (SCFA)-producing bacteria (Bifidobacterium ↑42 % and Ruminococcus ↑35 %). Interaction network analysis identified three functional microbial groups within the prebiotic metabolic pathway, revealing a fine metabolic relay among the three microbial guilds/groups, characterized by a flow of step-by-step degradation of prebiotics from microbes of Group 1, via microbes within Group 2, finally to those of Group 3. Notably, inter-individual variability in response was observed following NFFE intervention, and we identified two distinct host responder groups: high responders (HR, 50 %) and low responders (LR, 50 %) with the baseline characteristics of these two groups varying. HR group exhibited more significant improvements in aging-related physiological parameters, with enrichment of Ruminococcus 1 and Faecalibacterium in baseline microbiota, taxa known to degrade NFFE-derived prebiotics. These findings position NFFE as a promising dietary intervention against age-related decline via gut-microbiota modulation and comprehensive nutritional supplementation. The baseline-microbiota-dependent heterogeneity in response underscores the necessity of developing personalized formulations in future diet intervention trials.