Affiliations: [a] Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| [b] AZTherapies, Inc., Boston, MA, USA
| [c] Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| [d] Department of Radiology, Emek Medical Center, Afula, Israel
| [e] Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
| [f] Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel
| [g] Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
Correspondence:
[*]
Correspondence to: David R. Elmaleh, PhD, Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. Tel.:+1 617 318 3430; Fax:+1 617 848 8703; E-mails: delmaleh@mgh.harvard.edu and delmaleh@aztherapies.com.
Abstract: Progressive neurodegenerative diseases represent some of the largest growing treatment challenges for public health in modern society. These diseases mainly progress due to aging and are driven by microglial surveillance and activation in response to changes occurring in the aging brain. The lack of efficacious treatment options for Alzheimer’s disease (AD), as the focus of this review, and other neurodegenerative disorders has encouraged new approaches to address neuroinflammation for potential treatments. Here we will focus on the increasing evidence that dysbiosis of the gut microbiome is characterized by inflammation that may carry over to the central nervous system and into the brain. Neuroinflammation is the common thread associated with neurodegenerative diseases, but it is yet unknown at what point and how innate immune function turns pathogenic for an individual. This review will address extensive efforts to identify constituents of the gut microbiome and their neuroactive metabolites as a peripheral path to treatment. This approach is still in its infancy in substantive clinical trials and requires thorough human studies to elucidate the metabolic microbiome profile to design appropriate treatment strategies for early stages of neurodegenerative disease. We view that in order to address neurodegenerative mechanisms of the gut, microbiome and metabolite profiles must be determined to pre-screen AD subjects prior to the design of specific, chronic titrations of gut microbiota with low-dose antibiotics. This represents an exciting treatment strategy designed to balance inflammatory microglial involvement in disease progression with an individual’s manifestation of AD as influenced by a coercive inflammatory gut.
