CA-30, an oligosaccharide fraction derived from Liuwei Dihuang decoction, ameliorates cognitive deterioration via the intestinal microbiome in the senescence-accelerated mouse prone 8 strain

Abstract

Mounting evidence points to alterations in the gut microbiota-neuroendocrine immunomodulation (NIM) network that might drive Alzheimer’s Disease (AD) pathology. In previous studies, we found that Liuwei Dihuang decoction (LW) had beneficial effects on the cognitive impairments and gastrointestinal microbiota dysbiosis in an AD mouse model. In particular, CA-30 is an oligosaccharide fraction derived from LW. We sought to determine the effects of CA-30 on the composition and function of the intestinal microbiome in the senescence-accelerated mouse prone 8 (SAMP8) mouse strain, an AD mouse model. Treatment with CA-30 delayed aging processes, ameliorated cognition in SAMP8 mice. Moreover, CA-30 ameliorated abnormal NIM network in SAMP8 mice. In addition, we found that CA-30 mainly altered the abundance of four genera and 10 newborn genera. Advantageous changes in carbohydrate-active enzymes of SAMP8 mice following CA-30 treatment, especially GH85, were also noted. We further found that seven genera were significantly correlated with the NIM network and cognitive performance. CA-30 influenced the relative abundance of these intestinal microbiomes in SAMP8 mice and restored them to SAMR1 mouse levels. CA-30 ameliorated the intestinal microbiome, rebalanced the NIM network, improved the AD-like cognitive impairments in SAMP8 mice, and can thus be a potential therapeutic agent for AD.

The alteration of gut microbiome and metabolism in amyotrophic lateral sclerosis patients

“…As the most abundant microorganism being interdependent with human hosts, the gut microbiota not only constitutes a specialized microecosystem in gastrointestinal (GI) tract and harmonizes their relations dynamically, but is engaged in metabolic regulation and immune defense through the interplay with multiple distant organs and systems beyond the intestine 9 . In recent years, extensive studies have revealed that the microbiota–gut–brain axis is closely implicated in the pathophysiology of neurological diseases, which include but are not limited to Alzheimer’s disease 10 , autism spectrum disorder 11 , stroke 12 , 13 , multiple sclerosis 14 , and Parkinson’s disease 15 , 16 . As a crucial part of the axis, intestinal barrier dysfunction played an essential role in both gastrointestinal inflammatory diseases and neuropathology as well 17 .…”

Positive Effect of Lactobacillus acidophilus EG004 on Cognitive Ability of Healthy Mice by Fecal Microbiome Analysis Using Full-Length 16S-23S rRNA Metagenome Sequencing

“…In previous studies, a higher ratio of A. equolifaciens was found in the gut of patients with Alzheimer’s disease and autism spectrum disorder ( 46 , 47 ). In other studies, Roseburia hominis and Bacteroides_F pectinophilus were detected with a higher ratio in the patients with Alzheimer’s disease than that in healthy persons ( 48 , 49 ). When comparing the gut microbiome between the Parkinson’s disease group and normal group, we discovered Soleaferrea massiliensis more frequently in the patient group ( 50 ).…”

Gut microbial imbalance and neurodegenerative proteinopathies: from molecular mechanisms to prospects of clinical applications

“…Preventive effects on Aβ-induced cognitive deficits were also observed in mice orally administered with Bifidobacterium breve A1 strain prior to the intracerebroventricular injection of Aβ 25-35 [135]. Likewise, other probiotics (e.g., SLAB51, VSL#3, ProBiotic-4), prebiotics (e.g., fructooligosaccharide, xylooligosaccharides, ferulic acid), synbiotics (e.g., a mixture of xylooligosaccharides and Lactobacillus paracasei HII01) and, even dietary and traditional medicine interventions (e.g., oligosaccharide fractions derived from Liuwei Dihuang decoction) are potentially neuroprotective in different models of aging as SAMP8 mice [136][137][138] and other murine age-linked models of the AD etiopathogenesis [139][140][141][142][143][144][145][146], alleviating the main age-related symptoms of the disease and delaying its progression. This fact seems to reflect deeper changes at biochemical level, i.e., a decreased microglial activation, inflammation, oxidative stress and Aβ accumulation, increased levels of hippocampal BDNF and of genes involved in synapse processes [40,145,146].…”