Feb 17, 2021
George T. Grossberg, MD, conducts a Masterclass examining
emerging treatment options for Alzheimer’s disease that are tied to
the new research on the microbiome.
Dr. Grossberg is the Samuel W. Fordyce professor and director
of geriatric psychiatry in the department of psychiatry and
behavioral neuroscience at Saint Louis University.
He disclosed that he is a consultant for Acadia, Alkahest,
Avanir, Axovant, Axsome Therapeutics, Biogen, BioXcel, Genentech,
Karuna, Lundbeck, Novartis, Otsuka, Roche, and Takeda; receives
research support from the National Institute on Aging, Janssen, and
Genentech/Roche; performs safety monitoring for ANAVEX, EryDel,
Intra-Cellular Therapies, Merck, and Newron; and serves on the data
monitoring committee of ITI Therapeutics. Dr. Grossberg also serves
on the speakers’ bureau of Acadia.
Take-home points
- Dr. Grossberg discusses burgeoning research about treatment of
Alzheimer’s disease (AD) by altering the microbiota using diet and
medications.
- The microbiome refers to the entirety of microorganisms that
live throughout the body. Microbiota are those organisms that live
within the gut. Dysbiosis refers to a microbial imbalance, which
has been linked to numerous disorders, including inflammatory
diseases, psychiatric illness, obesity, diabetes, and more
recently, AD.
- The gut-brain axis describes the impact of microbiota and GI
tract health on the brain. Periodontal disease, as a marker of
inflammation and as part of the microbiome, is linked to AD.
- Increasing research into the role of the microbiome,
inflammation, and AD has revealed promising treatments. Sodium
oligomannate, a drug approved for mild to moderate AD in China,
has been shown to slow the progression of AD by remodeling the
microbiota and suppressing the production of specific amino acids
that promote neuroinflammation.
Summary
- The microbiota has many purposes, including digestion,
communication with the immune system, generation of signaling
peptides, refining vitamins, and producing antioxidants. Many
factors influence the microbiome, including diet, use of
antibiotics, exposure to breast milk as an infant, stress, and old
age.
- The gut microbiota can be altered by consuming “prebiotics,”
which are food sources that influence the composition of the
microbiota. These foods include fermented foods such as yogurt,
kombucha, sauerkraut, and kimchi. The Mediterranean diet also has
good sources of prebiotics.
- Birthing method (C-section versus vaginal birth) also
influences the microbiota; a recent study shows that an infant’s
microbiota after C-section can be altered by giving them an early
fecal transplantation from the mother.
- As further proof of the link between periodontal disease and
AD, a recent study identified the presence of Porphyromonas
gingivalis, a bacteria that causes gum disease, in the
brain in close proximity to the tau tangles of AD. Gingipain, the
toxin secreted by this bacteria, is found in high concentrations in
brains of individuals with AD.
- Dr. Grossberg reviewed his “recipe” for AD prevention and
treatment:
- Recommend adequate activity in four spheres: Physical, mental,
social, and spiritual.
- Treat and control all cardiovascular risk factors, including
smoking, obesity, diabetes, hypertension, and hyperlipidemia.
- Recommend good oral hygiene based on the increasing research
about the link of periodontal disease and AD.
- Recommend dietary changes, including a prebiotic or probiotic,
and the Mediterranean diet. Dietary changes may also include
supplements such as curcumin, B-complex multivitamin, and vitamin
E.
- Control exposure to air pollution as possible.
- Use a combination pharmacotherapy of an
N-methyl-D-aspartate antagonist and a cholinesterase
inhibitor for individuals with AD.
References
Jones ML et al. Gut
Microbes. 2014 Jul 1;5(4):446-57.
Askarova S et al. Front Cell
Infect Microbiol. 2020;10:104.
Beydoun MA et al.
J Alzheimers Dis. 2020;75(1):157-72.
Wang X et al. Cell Res.
2019 Oct;29(10):787-803.
Korpela K et al.
Cell. 2020 Oct 15;183(2):324-34.
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Show notes by Jacqueline Posada, MD, associate producer of the
Psychcast; assistant clinical professor in the department of
psychiatry and behavioral sciences at George Washington University,
Washington; and staff physician at George Washington Medical
Faculty Associates, also in Washington. Dr. Posada has no conflicts
of interest.
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