Thursday, August 9, 2018

Microbiome and the Brain

Special Communication: Microbiome Imbalances Promote Alzheimer’s and Parkinson’s Disease.
R.H. Bennett Ph.D., Applied Life Sciences LLC
This HATS Blog and other scientists describe the connection between the gut microbiome (MB) and a broad array of disease symptoms and specific diseases.  These conditions are by no means limited to the gut but involve the gut’s role in systemic inflammation and immune regulation. Brain function and health are not immune to the impacts of the MB.  This connection includes what is termed the “Gut-Brain Axis."
The Gut-Brain Axis
Simply stated, the brain affects the gut, and the gut affects the brain.  Some notable examples of this two-way axis include:
1.     Stress- the brain perceives stress and responds proportionally.  In chronic stress, the brain signals the pituitary to produce Adreno-corticotrophic Hormone (ACTH).  It moves in the circulation to the Adrenal Gland, and it turn it secretes Cortisol.  Cortisol has profound systemic, but in the gut, it will cause a reduction in mucus secretion.  As this protective production slows or ceases, opportunistic pathogens of the bowel called pathobionts begin to invade and disrupt the gut barrier.  The inflammatory response is systemic, and one manifestation is a disruption in higher brain functions like mood among others. Some forms of depression and anxiety disorders may result (Wong 2018).

2.     Dysbiosis Metabolites- A dysfunctional shift in the MB population can be associated with significant modification of the metabolites produced by the MB. Some of the chemicals are part of the regular MB, yet when there are substantial increases or decreases in any number of the metabolites an abnormal physiological response occurs.  This type of disruption can alter higher brain function is a significant clinical manner or the effect may be more subtle and can cause cognitive decline (Agusti 2018).

Recognition of the Gut-Brain Axis led researchers to some very recent and startling observations.   The MB Gut-Brain Axis has a significant and profound role in the development of Alzheimer’s and Parkinson’s Disease.  Yet again we see the dominant role the MB plays in health and disease.

Alzheimer’s Disease

A group of researchers in a consortium of 27 international institutions just published some profound data.  They show conclusively that alteration in the MB results in changes in the metabolites that arise from the degradation of bile-cholesterol acids in the intestine (Mahmoudiandehkordi 2018). In summary, they found:

1.     Bile acids (BA), products of cholesterol metabolism, are produced in the liver and are further metabolized by gut bacteria. They have major regulatory and signaling functions and seem dysregulated in Alzheimer disease (AD).”
2.     “Observed significantly lower serum concentrations of a primary BA (cholic acid CA) and increased levels of the bacterially produced, secondary BA, deoxycholic acid (DCA)."
3.     The increased DCA in circulation and lower BA resulted in the significant cognitive decline.

This figure shows the microbes in the colon metabolize bile acids and they get circulated back to the liver and then system-wide.  The restoration of a more balanced MB may well reduce the abnormal bile metabolites thus protecting the brain.
Other recent research found several of the significant bacterial taxa populations were quite different in patients with Alzheimer’s disease. It may be these taxa metabolize the bile-cholesterol acids resulting in increased DCA and decrease CA (Zhuang 2018).
This new research is clearly a breakthrough in our understanding of this terrifying disease.  The dysbiosis common to people on the Western Diet helps to explain why Alzheimer’s has become more common since the 1950ʻs. According to the CDC, the death rate from Alzheimer’s Disease increased 55% between 1999 and 2014 (

 By 2050, prevalence will quadruple by which time 1 in 85 persons worldwide will be living with the disease (Brookmeyer 2007).  Note the trend lines below are curved upward, indicating the attack prevalence is increasing at an increasing rate.  This may well reflect the globalization of the commercial Western Diet.

Parkinson’s Disease and the Microbiome
 This disease unlike Alzheimer’s attacks nerve-muscle motor functions of the brain but similar in that it is progressive.  Research detailing the MB of Parkinson’s Disease (PD) and healthy persons revealed some conclusive trends (Brookmeyer 2007).   When other factors such as age, weight, diet, and medications were accounted for statistically, many types of MB bacteria populations differ in the PD patients.  The medicines are taken also modify the MB, so that influence had to be accounted for as well.
 To evaluate the functional differences between PD patients and controls the metabolic pathways of the unique differences in the MB had to be assessed.  Of the 136 metabolic pathways of the bacteria, 26 were different between cases and controls. Precisely what these unique metabolic activities mean is not known at this time. However, it is more than likely that one or more contributes to the onset and progression of PD.  However, one difference was the production of short chain fatty acids (SCFA) one type of bacteria was significantly reduced in PD patients, and that is consistent with the reduction of SCFAʻs.
 This type of alteration of the SCFA correlates to increased inflammatory signaling and one that may alter the microglial cells of the brain.  This is a predominant theory of PD pathogenesis.
 The Take-Away
 It will be many more years before this pathology becomes very clear and definitive.  However garden-variety wisdom suggests we not wait until then. The data connecting the MB to brain health is robust.  To help prevent dysbiosis that may be a precursor to either of these insidious neurodegenerative diseases, we employ the Eubiotic Strategy.
 Eubiotic Strategy
 Eubiosis (good biome)  is the balanced and fully functional MB.  The Eubiotic Strategy is simple.
 1.     Choose the Mediterranean Diet over the Western Diet
a.     Eliminate refined sugars
b.     Reduce Saturated Fats
c.      Reduce the Glycemic Load
                                         i.     Much less simple starches
d.     Greatly increase soluble fiber intake
                                         i.     Fruits
                                       ii.     Prebiotics
2.     Avoid antibiotics unless the physician demonstrates necessity.
3.     Consume HATS probiotics (see the early blogs) at least 3 days a week
a.     Both encapsulated and non protected to provide some activity for the small intestine where some bile and cholesterol metabolism occurs
4.     Consume Defatted Colostrum products with the probiotics to further modulate inflammation
5.     Share this information widely. People matter; the food industry must adapt.

Agustí, Ana, et al. "Interplay Between the Gut-Brain Axis, Obesity and Cognitive Function." Frontiers in neuroscience 12 (2018): 155.

Brookmeyer, Ron, et al. "Forecasting the global burden of Alzheimer’s disease." Alzheimer's & Dementia 3.3 (2007): 186-191.

Mahmoudiandehkordi, Siamak, et al. "Altered Bile Acid Profile Associates with Cognitive Impairment in Alzheimer's Disease: An Emerging Role for Gut Microbiome." bioRxiv (2018): 281956.

Mazmanian, Sarkis K. "The gut microbiome connection to Parkinson’s disease." The FASEB Journal 32.1_supplement (2018): 101-4.

Pistollato, Francesca, Sandra Sumalla Cano, Iñaki Elio, Manuel Masias Vergara, Francesca Giampieri, and Maurizio Battino. "Role of gut microbiota and nutrients in amyloid formation and pathogenesis of Alzheimer disease." Nutrition reviews 74, no. 10 (2016): 624-634.

Wong, Ma-Li. "The inflammasome and the microbiota-gut-brain axis." Neurology, Psychiatry, and Brain Research 29 (2018): 25.

Zhuang, Zhen-Qian, et al. "Gut Microbiome is Altered in Patients with Alzheimer’s Disease." Journal of Alzheimer's Disease Preprint (2018): 1-10.

1 comment:

  1. We really enjoy this blog , and are learning a lot and teaching a lot abut our microbiome .. Education is key , looking forward to learning more Dr. Bennett .. thank you !!