The microbiota-gut-brain-axis (MGBA) is a bidirectional communication network between gut microbes and their
host. Many environmental and host-related factors affect the gut microbiota. Dysbiosis is defined as compositional and
functional alterations of the gut microbiota that contribute to the pathogenesis, progression and treatment responses to
disease. Dysbiosis occurs when perturbations of microbiota composition and function exceed the ability of microbiota and its
host to restore a symbiotic state. Dysbiosis leads to dysfunctional signaling of the MGBA, which regulates the development
and the function of the host’s immune, metabolic, and nervous systems. Dysbiosis-induced dysfunction of the MGBA is
seen with aging and stroke, and is linked to the development of common stroke risk factors such as obesity, diabetes, and
atherosclerosis. Changes in the gut microbiota are also seen in response to stroke, and may impair recovery after injury.
This review will begin with an overview of the tools used to study the MGBA with a discussion on limitations and potential
experimental confounders. Relevant MGBA components are introduced and summarized for a better understanding of agerelated changes in MGBA signaling and its dysfunction after stroke. We will then focus on the relationship between the
MGBA and aging, highlighting that all components of the MGBA undergo age-related alterations that can be influenced by
or even driven by the gut microbiota. In the final section, the current clinical and preclinical evidence for the role of MGBA
signaling in the development of stroke risk factors such as obesity, diabetes, hypertension, and frailty are summarized, as
well as microbiota changes with stroke in experimental and clinical populations. We conclude by describing the current
understanding of microbiota-based therapies for stroke including the use of pre-/pro-biotics and supplementations with
bacterial metabolites. Ongoing progress in this new frontier of biomedical sciences will lead to an improved understanding
of the MGBA’s impact on human health and disease. CLICK TO REVIEW
Key Words: aging ◼ brain-gut axis ◼ dysbiosis ◼ microbiota ◼ risk factors ◼ stroke