Mice genetically prone to developing dementia demonstrate a distinct gut bacteria profile that is enhanced by a coincident high-fat diet, a new study finds.
Background to the gut-brain barrier
There is growing evidence for gut bacteria contributing to the onset of neurological disorders, through what has been termed the ‘gut-brain axis’. The gut microbiota produce many different metabolites which can penetrate the intestinal barrier, circulate in the bloodstream and cross the blood-brain barrier to exert their effects on the central nervous system. Therefore, detrimental changes in the gut flora could influence alterations in brain function and in neurological development. The involvement of the intestinal microbiota has been well investigated in conditions such as autism and Parkinson’s disease, but seemingly not in dementia or Alzheimer’s disease.
Using a mouse model proven to develop Alzheimer’s disease (AD) called 3xtg, Sanguinetti et al. examined the composition and diversity of gut bacteria in the mice at the pre-dementia stage compared to a control. In the study, the 3xtg mice demonstrated typical metabolic features that precedes human dementia.
Since obesity is a major risk factor for dementia and AD, the group also assessed the microbiota in mice fed a high-fat diet vs normal diet in both the 3xtg and control groups. High-fat diets have previously been shown to impact on the gut microbiota.
For clarification, the mice were grouped as follows: normal diet-fed (ND), high-fat diet fed (HFD), normal diet-fed 3xtg (3xtg), and high-fat diet fed 3xtg (3xtg-HFD)
The research team identified significant patterns in the microbiota of 3xtg mice compared to the control:
- The number of different bacterial species was lower in 3xtg mice vs ND
- In a normal gut, bacterial composition from one intestinal segment to another would be diverse due to their different functions. This diversity was lost between colon to caecum in the 3xtg mice
- The Bifidobacteriaceae bacteria, which are positively linked with cognitive function, were depleted in 3xtg mice vs ND
Together with other bacterial alterations found by Sanguinetti et al., some of these observations are associated with inflammatory states, which is relevant to AD.
The group also obtained interesting results from mice given a high-fat diet:
- HFD mice demonstrated a modified gut bacterial composition and a decreased bacterial richness, when compared to ND mice
- Increases in Clostridium and Staphylococcus were observed in HFD mice vs ND. Such bacteria are associated with adverse effects
- Beneficial Bifidobacteriaceae and Lactobacillaceae were depleted in HFD mice vs ND
In the 3xtg and HFD mice, changes in certain bacteria occurred in a similar direction, leading to dramatic summative results from the 3xtg-HFD mice compared to 3xtg or HFD mice alone. For example, there was a distinct excess of Clostridium in 3xtg-HFD mice.
In summary, mice genetically prone to neurodegenerative disease exhibit a pre-disease alteration in gut bacteria that is exacerbated by a high-fat diet. A characteristic microbiota ‘signature’ involving changes in certain bacterial families emerged from the study, with the changes likely to affect brain health.
The pre-dementia bacterial profile determined by Sanguinetti et al. could prove to be generally predictive of Alzheimer’s disease, and thus the study has great implications. Future work is needed to establish a cause-effect relationship, and to determine whether this theory translates to humans.