New Research on Alzheimer’s and Microbiome Alterations

This morning I stumbled across some interesting research on alterations in the microbiome and Alzheimer’s Disease (AD).[i]  I have written before about recent studies suggesting that such alterations lead to the amyloid deposits in the brain that are characteristics of the disease. Researchers at the University of Wisconsin-Madison, along with scientists in both Sweden and the UK, analyzed the biomes of 50 people (25 with the disease and 25 health people) by gene sequencing of the bacteria from fecal samples.  Those with AD had markedly less diversity of species: in particular, they showed a decrease in Firmicutes and Bifidobacterium, and an increase in Bacteroidetes.

The authors concluded that, “The decreased richness and diversity in our study broadly parallels results observed in other conditions linked to gut microbiome alterations, including obesity, diabetes, IBD, and Parkinson’s disease….While the specific bacteria responsible for these compositional and functional alterations may differ between conditions, it has been proposed that these broad-scale changes in gut microbiota (often referred to as “dysbiosis”) may play important roles in disease progression and maintenance, potentially through immune activation and systemic inflammation.”

What I found particularly interesting is that the authors look at the specific bacterial changes and relate them to possible mechanisms of action. Two examples:

1. A reduction in the class of Firmicutes is also associated with type 2 diabetes, and “…insulin resistance is associated with decreased cerebral glucose metabolism and increased amyloid deposition…” The authors suggest that this is a potential mechanism by which the microbiome alterations affect the brain.

 

2. An increase in the phylum Bacteroidetes, including the genus Bacteroides, is also associated with both type 2 diabetes, but also Parkinson’s disease, another neurodegenerative disorder.  The outer membrane of this type of “gram-negative” bacteria contains lipopolysaccharides (LPS) which is highly proinflammatory (and, in fact, is often used in animal experiments to induce colitis and the like).  Recent postmortem studies of the brains of people with AD showed LPS and gram-negative bacterial fragments in the amyloid plaques. [i]

By the way, there was actually some good news in this paper.  As noted above, the researchers found decreased amounts of Bifidobacterium species.  These are highly anti-inflammatory and improve the health of the gut’s mucosal barrier (keeping it from becoming leaky).  In a small, 12-week-long study of people with severe dementia, a probiotic that contains Bifidobacterium showed improvement in mental state examination scores.

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[i] Vogt, NM, et. al. Gut microbiome alterations in Alzheimer’s disease. Scientific Reports 7. Article number: 13537  2017.

 

[ii] Vogt, NM, et. al. Gut microbiome alterations in Alzheimer’s disease. Scientific Reports 7. Article number: 13537  2017.