Title:Gut Microbiome and Circadian Interactions with Platelets Across Human
Diseases, including Alzheimer’s Disease, Amyotrophic Lateral Sclerosis,
and Cancer
Volume: 23
Issue: 28
Author(s): George Anderson*
Affiliation:
- Department of Research, CRC Scotland & London, Eccleston Square, London, SW1V 1PG, UK
Keywords:
Platelets, Mitochondria, Melatonin, N-acetylserotonin, Aryl hydrocarbon receptor, Gut microbiome, Circadian, Neurodegeneration, Cancer, PLAU.
Abstract: Platelets have traditionally been investigated for their role in clot formation in the
course of cardiovascular diseases and strokes. However, recent work indicates platelets to be an integral
aspect of wider systemic processes, with relevance to the pathophysiology of a host of diverse
medical conditions, including neurodegenerative disorders and cancer. This article reviews
platelet function and interactions with the gut microbiome and circadian systems, highlighting the
role of the platelet mitochondrial melatonergic pathway in determining platelet activation, fluxes
and plasticity. This provides a number of novel conceptualizations of platelet function and mode
of interaction with other cell types, including in the pathoetiology and pathophysiology of diverse
medical conditions, such as cancer, Alzheimer’s disease, and amyotrophic lateral sclerosis. It is
proposed that a platelet-gut axis allows platelets to contribute to many of the pathophysiological
processes linked to gut dysbiosis and gut permeability. This is at least partly via platelet sphingosine-
1-phosphate release, which regulates enteric glial cells and lymphocyte chemotaxis, indicating
an etiological role for platelets in a wide array of medical conditions linked to alterations in
the gut microbiome. Platelets are also an important regulator of the various microenvironments
that underpin most human medical conditions, including the tumor microenvironment, neurodegenerative
diseases, and autoimmune disorders. Platelet serotonin release regulates the availability
of the mitochondrial melatonergic pathway systemically, thereby being an important determinant
of the dynamic metabolic interactions occurring across cell types that underpin the pathoetiology
of many medical conditions. In addition, a number of novel and diverse future research directions
and treatment implications are proposed.