Konjac oligo-glucomannan ameliorate cognition impairments of Aβ1-42 induced Alzheimer’s disease in mice by targeting microbiota-SCFAs-brain axis

• KGM and KOGM significantly ameliorate the cognitive dysfunction of AD mice. • KOGM shows better effects than KGM on improving cognitive function of AD mice. • KOGM affects the growth of Alistipes , and upregulate the production of SCFAs. • KOGM regulates the abundance of function and metabolic pathways of gut microbiota. Here, the effects of konjac glucomannan (KGM) and oligo-glucomannan (KOGM) on improving Aβ-induced Alzheimer’s disease (AD) was investigated. Behavioral test suggested that both KGM and KOGM could significantly increase the spatial learning and memory of AD mice, with the latter be more effective. Biochemical examinations revealed that KOGM inhibited the Aβ accumulation and hyperphosphorylation of Tau protein, upregulated bdnf , trkb , pi3k and akt , and downregulated gsk3β . Metagenomic sequencing indicated that KOGM regulated the diversity and function of microbiota, especially bacteria belonging to Alistipes , thus promoting the production of short chain fatty acids (SCFAs), as well as their cyclic levels. The strong relationships among gut microbiota, SCFAs and physiological index for AD suggested that KOGM could activated BDNF/PI3K/GSK3β pathway to ameliorate AD, by enhancing SCFAs levels. This study emphasized the KOGM as a potential prebiotic to prevent AD progression, through the gut-brain axis and constitutes a novel approach in AD treatment.