The neuromodulatory effects of flavonoids and gut Microbiota through the gut-brain axis

Abstract

Recent investigations show that dietary consumption of flavonoids could potentially confer neuroprotective effects through a variety of direct and indirect mechanisms. Numerous flavonoids have been shown to cross the BBB and accumulate within the central nervous system (CNS). Some of these compounds purportedly counteract the accumulation and deleterious effects of reactive oxygen species, fostering neuronal survival and proliferation by inhibiting neuroinflammatory and oxidative stress responses. Moreover, several studies suggest that gut microbiota may participate in regulating brain function and host behavior through the production and modulation of bioactive metabolites. Flavonoids may shape gut microbiota composition by acting as carbon substrates to promote the growth of beneficial bacteria that produce these neuroprotective metabolites, consequently antagonizing or suppressing potential pathogens. By influencing the microbiota-gut-brain axis through this selection process, flavonoids may indirectly improve brain health. This review examines the current state of research into the relationship between bioactive flavonoids, gut microbiota, and the gut-brain axis.

Modulatory Effects of Phytochemicals on Gut–Brain Axis: Therapeutic Implication

“…Several studies in animal models have demonstrated that flavonoids reduce oxidative stress, decrease neuroinflammation, stimulate neurogenesis, activate neuronal regeneration, and protect the nervous system through several various mechanisms [ 70 , 71 ]. Some specific flavonoids have the ability to cross the BBB and provide direct neuroprotective effects by inhibiting oxidative stress, reducing inflammatory responses, regulating neuronal metabolism, and promoting neuronal regeneration [ 72 ]. Additionally, some studies suggest that flavonoids can indirectly protect the nervous system by modulating the composition and metabolites of gut microbiota that have an impact on the function of the GBA [ 73 , 74 ].…”

“…The indirect effects of flavonoids, such as their ability to modulate gut microbiota and the GBA, may have a more significant impact than their direct effects on the CNS [ 72 ]. Research has shown that flavonoids have the ability to control the growth of specific bacterial groups and modify the structure and function of gut microbiota [ 75 ].…”

Flavonoids as anxiolytics in animal tests: Bibliometry and meta-analysis of the effects of flavonoids on anxiety-like behavior in animal tests

“…Experimental results show that flavonoids and their conjugates derivatives may cross the bloodbrain barrier and exert pharmacological action on the central nervous system (Jäger & Saaby, 2011;Youdim et al, 2003) by activating neuronal signaling pathways (Spencer, 2007) and neurotransmitter systems (i.e., serotonergic, GABAergic, noradrenergic, and dopaminergic, among others) involved in neuropsychiatric disorders as anxiety and depression (German-Ponciano et al, 2018;C. Wang et al, 2023;H. Wang et al, 2023).…”