Soluble fermentable dietary fiber attenuates age-related cognitive impairment via neuroimmune and antioxidant modulation: evidence from multilevel analyses in populations and aging mouse models.

Higher total dietary fiber intake was nonlinearly associated with better cognitive performance in older adults, with approximately 15 g/day as the threshold for maximal benefit.

• Analysis was conducted in 2,350 older adults from NHANES (2011-2014).
• Weighted regression and spline modeling were used to assess the association between total dietary fiber intake and cognitive performance.
• The association was nonlinear, with ~15 g/day identified as the threshold beyond which maximal cognitive benefit was observed.
• The study population consisted of older adults, making findings relevant to age-related cognitive impairment.

Inulin supplementation as a representative SFDF improved memory, learning, and anxiety-like behavior in a D-galactose-induced aging mouse model.

• D-galactose was used to induce an aging model in mice, and inulin was administered as the SFDF intervention.
• Behavioral outcomes assessed included memory, learning, and anxiety-like behavior.
• SFDF-treated mice showed improvements across all three behavioral domains compared to untreated aging mice.
• These findings were part of the animal-level evidence in the multilevel analysis framework.

SFDF supplementation reduced pro-inflammatory cytokines and lipid peroxidation while enhancing antioxidant defenses in aging mice.

• Specific cytokines measured included IL-6 and TNF-α, both of which were reduced following SFDF treatment.
• Lipid peroxidation, a marker of oxidative stress, was also alleviated by SFDF supplementation.
• Antioxidant defenses were enhanced in mice receiving SFDF compared to control aging mice.
• These findings suggest dual neuroimmune and antioxidant mechanisms underlying the cognitive benefits of SFDF.

Single-nucleus RNA sequencing analysis revealed that 5% SFDF intervention was associated with a shift toward a reparative Mic.7 microglial subtype in naturally aged mice.

• An independent single-nucleus RNA-seq dataset of naturally aged mice receiving a 5% SFDF intervention was analyzed.
• The Mic.7 microglial subtype was characterized as enriched for immune regulation and oxidative defense programs.
• The SFDF intervention was associated with a shift toward this reparative Mic.7 subtype, indicating microglial state remodeling.
• This single-cell level evidence provided mechanistic insight into how SFDF may modulate neuroimmune responses during aging.

Age-related cognitive impairment represents an urgent public health concern with limited therapeutic options, and SFDF represents a safe and accessible nutritional approach.

• SFDF was described as 'a safe, accessible nutritional factor' that may support cognition through microglial remodeling and antioxidant defense.
• Prior to this study, the dose-response effects and cellular mechanisms of SFDF on cognition remained unclear.
• The study used a multilevel analytical framework combining population-level (NHANES), animal model, and single-cell RNA-seq evidence.
• Dietary fiber was highlighted as 'a scalable nutritional strategy to support healthy cognitive aging.'