Amelioration of Alzheimer’s Disease by Gut-Pancreas-Liver-Brain Interaction in an App Knock-In Mouse Model

Abstract

In this study, we observed disease progression, changes in the gut microbiota, and interactions among the brain, liver, pancreas, and intestine in a mouse model of Alzheimer’s disease (AD), in addition to attempting to inhibit disease progression through the dietary supplementation of L-arginine and limonoids. Wild-type mice (WC) and AD mice were fed a normal diet (AC), a diet supplemented with L-arginine and limonoids (ALA), or a diet containing only limonoids (AL) for 12–64 weeks. The normal diet-fed WC and AC mice showed a decrease in the diversity of the gut microbiota, with an increase in the Firmicutes/Bacteroidetes ratio, and bacterial translocation. Considerable bacterial translocation to the pancreas and intense inflammation of the pancreas, liver, brain, and intestinal tissues were observed in the AC mice from alterations in the gut microbiota. The ALA diet or AL diet-fed mice showed increased diversity of the bacterial flora and suppressed oxidative stress and inflammatory responses in hepatocytes and pancreatic cells, bacterial translocation, and neurodegeneration of the brain. These findings suggest that L-arginine and limonoids help in maintaining the homeostasis of the gut microbiota, pancreas, liver, brain, and gut in AD mice.

Nervonic acid reduces the cognitive and neurological disturbances induced by combined doses of D‐galactose/AlCl3 in mice

“…According to the previous research methods, the pathological histomorphology of liver and brain tissues was analyzed (Minamisawa et al, 2021 ). Briefly, after dehydration, dewaxing, embedding, sectioning, staining, and sealing, the liver and brain sections were obtained.…”

Jiedu-Yizhi Formula Alleviates Neuroinflammation in AD Rats by Modulating the Gut Microbiota

“…It may be related to the reduced A β deposition and downregulated inflammatory levels in the brain of AD mice [ 3 ]. L-Arginine and limonoids can increase the gut microbial diversity of App < NL-G-F > knock-in AD mice, thereby improving neuroinflammation and neurodegeneration [ 17 ]. Electroacupuncture in Baihui (GV20) and Yintang (GV29) of SAMP8 mice can increase the abundance of Bacteroides in their gut, reduce the abundance of Clostridium , and increase the ratio of Bacteroides to Clostridium .…”