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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