Over 26,000 protein-coding genes, that’s what The Human Genome Project determined.  While that seems like a lot, rice has about 46,000 genes.  So how is it that we are more complex than a grain of rice?  Well, it’s probably because the bacteria in our guts (our microbiota) encode about 4,000,000 genes (Human Microbiome Project Consortium, 2012; Venter et al., 2001).  Take that rice!
Studies showing links between the microbiota and the brain are increasing in number and frequency.  A study from 2012 shows that germ-free mice had leaky blood brain barriers, a condition that would allow pathogens into the brain.  In fact, one study from 2016 has shown increased levels of bacteria in the brains of people with Alzheimer’s.  Fortunately, attempts to change the composition of the microbiota have shown promise as a prevention or treatment for Alzheimer’s (something we will be looking at in more detail ).

So what does the microbiota of someone with Alzheimer’s look like?

A Simple Summary

This 2017 study from the University of Wisconsin compared the microbiota of 25 people diagnosed with Alzheimer’s and 25 age and sex-matched control participants.  The Alzheimer’s group showed decreased levels of “good” bacteria and increased levels of “bad” bacteria.

More Detail

The two groups were similar in their diets as assessed by their scores on a 15-item food questionnaire.  ApoE 4 was more prevalent in the Alzheimer’s group.

The microbiota of the Alzheimer’s group was not as rich.  It showed significantly altered levels of 82 operational taxonomic units (OTUs), 14 of which were more abundant, and 68 less abundant.  Of those, 13 at the genus level showed strong correlations between the abundance of the bacteria and biomarkers for Alzheimer’s in the subject’s spinal fluid.  This correlation was also true for the healthy control group.

The biomarkers were chosen for their ability to indicate amyloid-beta levels (both Aß-40 and Aß-42), and levels of phosphorylated tau (p-tau), and the ratio of  p-tau to Aß-42.  As noted earlier, as good bacteria decreased these biomarkers of Alzheimer’s pathology increased and as the bad bacteria increased these markers increased again.

The observed decrease in richness of the microbiota echoes results observed in other conditions that exhibit microbiota alterations, such as obesity, diabetes, and Parkinson’s.  Others have suggested that dysbiosis (the change in the microbiota from balanced to unbalanced) “may play important roles in disease progression and maintenance, potentially through immune activation and systemic inflammation.”

The body of evidence is pointing towards a two-way street of communication between the gut and the brain (often referred to as the gut-brain axis).   Improve one and you improve the other.  Of course, the easier thing to do here is probably going to be improving the health of your microbiota.

Into The Weeds

I won’t go all the way into the weeds as it gets pretty dense in there with individual bacterium, but this will include the more important findings.  Here again is a link to the original study Gut microbiome alterations in Alzheimer’s disease.

The microbiota change at the phylum level showed a decrease in Firmicutes and Actinobacteria.  Firmicutes reduction has been reported in diabetes and obesity.  A reduction in Actinobacteria, mainly because of much lower abundance of Bifidobacterium, is associated with an increase in inflammation and the permeability of the intestines.

The second change at the phylum level was an increase in Bacteroidetes.  At the genus level Bacteroides have been shown to increase in the guts of individuals with diabetes, and Parkinson’s.   Back to the phylum level – Bacteroidetes include a large and diverse group of gram-negative bacteria in the gut.  Gram-negative bacteria contain lipopolysaccharide (LPS) in their outer membrane.  If gram-negative bacteria escape the gut and enter the bloodstream the LPS can trigger systemic inflammation and encourage the release of pro-inflammatory cytokines.  LPS has also been implicated in worsening the pathologies of Aß and tau.

Both phylum level microbiota changes in the Alzheimer’s group were associated with diseases linked to Alzheimer’s and to inflammation and other Alzheimer’s pathologies.

Connecting the dots, the reduction of Bifidobacterium increases inflammation and increases the permeability of the gut.  Increased permeability of the gut allows gram-negative bacteria into the blood stream where the LPS from its outer membrane triggers more inflammation and then crosses the blood brain barrier where it combines with plaque deposits and exacerbates tau pathology.

Whether Alzheimer’s alters our microbiota or dysbiosis leads to Alzheimer’s, the solution is probably the same – improve the microbiota.