Supplementation of glucomannans ameliorate high-fat diet–induced cognitive impairment via a gut microbiota–metabolite–glutamatergic synapse axis

Mar 29, 2026International journal of biological macromolecules

Glucomannan supplements may improve high-fat diet-related thinking problems through gut bacteria and brain signaling

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Abstract

All glucomannans improved behavioral performance and reduced hippocampal neuronal damage.

High-fat diets are linked to cognitive impairment and increased neurodegeneration risk.
Glucomannans from various sources, including Aloe vera, show potential in mitigating these effects.
Aloe vera-derived glucomannan had the highest level of acetylation and the most significant impact on cognitive function.
Glucomannans alter gut microbiota and blood metabolites, influencing synaptic pathways in the brain.
Two metabolites, N-acetyl-L-glutamic acid and N-acetylneuraminic acid, were found to be elevated in feces and serum and correlated with improved cognitive outcomes.
Animal experiments indicated that these metabolites may replicate the neuroprotective effects of glucomannans.

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High-fat diets (HFDs) induce cognitive impairment and increase neurodegeneration risk. Glucomannans (GMs) targeting the gut-brain axis are a promising dietary strategy, but the efficacy of specific glucomannans and their mechanisms remain unclear. This study aimed to prepare GMs from various food sources, including Dendrobium officinale, konjac, and Aloe vera, and evaluate their potential to mitigate HFD-induced cognitive impairment. All the GMs improved behavioral performance, attenuated hippocampal neuronal damage, and enhanced glutamatergic synapse density, with the Aloe vera-derived GM-characterized by the highest degree of acetylation and mannose/glucose ratio-exerting the most pronounced effects. Multi-omics network analyses revealed that GMs reshape the gut microbiota and circulating metabolome, thereby modulating glutamatergic synaptic pathways in the hippocampus. Data-driven integration further identified two GM-associated metabolites-N-acetyl-L-glutamic acid and N-acetylneuraminic acid-that were consistently upregulated in both feces and serum and positively correlated with cognitive outcomes. Subsequent animal experiments showed that these metabolites could recapitulate the neuroprotective effects of GMs. Collectively, our findings suggest that GMs can ameliorate HFD-induced cognitive impairment via a gut microbiota-metabolite-glutamatergic synapse axis.

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Supplementation of glucomannans ameliorate high-fat diet–induced cognitive impairment via a gut microbiota–metabolite–glutamatergic synapse axis

Abstract

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