By studying both healthy and diseased mice, researchers from the University of Lund in Sweden found that mice suffering from Alzheimer's have a different composition of gut bacteria compared to mice that are healthy.
In addition to comparing the gut composition of mice with and without Alzheimer’s, the Swedish researchers also studied Alzheimer's disease in mice that completely lacked gut bacteria – finding they had a significantly lower level of beta-amyloid plaque that are associated with Alzheimer’s development.
"Our study is unique as it shows a direct causal link between gut bacteria and Alzheimer's disease. It was striking that the mice which completely lacked bacteria developed much less plaque in the brain," said lead researcher Frida Fåk Hållenius.
Furthermore, when these bacteria free mice were then given intestinal bacteria from mice with Alzheimer’s Hållenius and colleagues saw that the mice developed more beta-amyloid plaques than when they were given bacteria from healthy mice.
“Our results indicate a microbial involvement in the development of beta-amyloid pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases,” wrote the authors.
Indeed, the association of bacterial taxa with cerebral pathology observed in mice suggests that specific microbes may be involved in progression of cerebral beta-amyloidosis and that this may lead to the onset or progression of Alzheimer’s disease.
“Obviously, the clinical translation of these preclinical results bears the potential for opening a new area for the treatment and prevention of AD pathology and ultimately other neurodegenerative disorders,” the Swedish team wrote – adding that the results further support an emerging view that microbiota contribute to the development of a wide range of neurological and neurodegenerative diseases “well beyond metabolic syndrome, diabetes and obesity.”
Hållenius and colleagues measured the relative abundance of microbes in healthy mice and those with a mouse model of Alzheimer’s disease known as APP transgenic mice.
They found that the abundance of at least two major phyla (Firmicutes and Bacteroidetes) in the faecal microbiota was significantly altered in APPPS1 mice compared to healthy counterparts (non-transgenic wild-type mice).
At genus level, Allobaculum and Akkermansia were decreased and unclassified genera of Rikenellaceae and S24-7 increased, said the team.
“Subsequently we generated germ-free APP transgenic mice and found a drastic reduction of cerebral Aβ amyloid pathology when compared to control mice with intestinal microbiota,” said the authors.
They added that colonisation of germ-free APP transgenic mice with microbiota from conventionally-raised APP transgenic mice increased amyloid plaques and signs of Alzheimer’s, while colonisation with microbiota from wild-type mice did not lead to increases in plaques.
“Remarkably, we observed significant alterations in the brain’s immune response in GF-APPPS1 mice,” wrote the team. “Our results showing reduced microgliosis and changes in the brain cytokine profile are in line with a recent publication demonstrating that germ-free mice show immature microglia and reduced pro-inflammatory cytokine production.”
“Our study strongly argues for a role of gastro-intestinal microbes in the development of cerebral Aβ amyloidosis,” said the team.
The Swedish team, along with other researchers in Europe, will continue to study the role of bacteria in the development of Alzheimer's disease, and test new types of preventive and therapeutic strategies based on the modulation of the gut microbiota through diet and new types of probiotics, they said.
Source: Scientific Reports
Volume 7, Article number: 41802, doi: 10.1038/srep41802
“Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota”
Authors: T. Harach, et al