Perspektywa osi jelitowo-mózgowej w kontekście wpływu kwiatów konopi na barierę krew-mózg

Gut-brain-axis perspective on the impact of Cannabis flos on the blood-brain-barrier
Inflammation within the central nervous system (CNS), known as neuroinflammation, is a critical factor in the
pathogenesis of neurodegenerative diseases such as Parkinson's and Alzheimer's disease, mood disorders, e.g.
depression, anxiety, and cognitive dysfunctions. The development of inflammation in the CNS is multifaceted, but the
most commonly mentioned factors include a decline in the integrity of the blood-brain barrier and inflammation initiated
by non-neuronal microglial cells.
Recently, the bidirectional communication pathway between the gut microbiota and the CNS, known as the microbiotagut-
brain axis, has attracted increasing attention. Moreover, recent reports indicate significant changes in the diversity of
the gut microbiota in the course of neurodegenerative diseases and depression.
The diversity of the gut microbiota largely depends on many factors, not only dietary components and synthetic drugs but
also natural products and specialised plant metabolites used for their medicinal properties. On the other hand, in recent
years, more attention has been paid to the role of the gut microbiota in assessing the efficacy and mechanisms of action
of established therapies, including those based on plant-derived products. An essential aspect of research on the
pharmacokinetics and bioavailability of orally administered herbal medicines is the formation of postbiotic metabolites,
often with greater therapeutic potential compared to the parent compounds. From this perspective, including the gut
microbiota as a critical factor influencing the medicinal properties of herbal remedies offers an opportunity to fill the
knowledge gap resulting from inconsistencies between the pharmacokinetics of individual specialised plant metabolites
and the effects observed in vivo.

Natural raw materials offer promising therapeutic opportunities due to their complex structure and interaction with gut
microbiota. Cannabis sativa L. has gained particular attention due to its multifaceted therapeutic effects attributed to
cannabinoids, terpenes and flavonoids. Due to the chemical profile of Cannabis flos (CF) specialised metabolites, recent
researches focus on the potential use of this plant material in neurodegenerative diseases, e.g. Parkinson's disease, as
well as mood disorders - anxiety and depression. Although vaporisation is the most common route of CF administration,
current estimates suggest that a significant proportion (25%) of cannabis users use “edible” preparations, which may
include infusions and tinctures, as well as plant material in the form of tablets or capsules. This is especially common in
patients who cannot inhale due to lung disease, trouble handling vaporiser devices, or due to their personal preferences.
Nevertheless, the interactions of oral Cannabis flos formulations with the gut microbiota and the pharmacological
potential of their gut metabolites have not been elucidated.
Considering the unresolved question of the participation of gut microbiota in the metabolism of orally administered CF
preparations (micronised raw material, infusions, tinctures), the proposed project aims to conduct a metabolomic
assessment of postbiotic metabolites derived from oral CF formulations, produced by ex vivo intestinal microbiota
cultures and to clarify their potential in vitro activity.
This will allow us to verify the research hypothesis that Cannabis flowers may be a source of various postbiotic
metabolites that affect the blood-brain barrier and modulate neuroinflammation.
Through a comprehensive range of experimental approaches, our scientific project will allow us to understand previously
unexplored aspects concerning the chemical structures of postbiotic CF metabolites, the effect of this plant material on
the diversity and metabolism of human gut microbiota, as well as the effect of CF gut metabolites on the blood-brain
barrier and microglial cell functions. The obtained results will allow us to better understand the mechanisms of action of
CF plant material and its formulations in the context of neuroinflammatory-based diseases. Moreover, the
implementation of the project assumptions will also allow us to assess whether any of the postbiotic CF metabolites can
be used as a matrix for the development of new therapeutic agents for neuroinflammatory-based diseases.