Stefania Blasa MicrobiotaMi

MicrobiotaMi Comment 05_21  by Stefania Blasa

Related Journal Article: Diet-dependent gut microbiota impacts on adult neurogenesis through mitochondrial stress modulation

Brain Commun. 2020 Oct 6;2(2):fcaa165. doi: 10.1093/braincomms/fcaa165. eCollection 2020

Dietary changes induce alterations in adult neurogenesis via mitochondrial pathways

 

The importance of diet in brain health and neurological function has gained increasing interest in the last years. Dietary factors are well known to influence the composition of gut microbiota, which regulates several brain functions through the gut microbiota-brain axis and whose imbalance lead to pathological disorders such as depression, anxiety, autism and neurodegenerative diseases; in fact, it was largely demonstrated that unbalanced diet such as calorie-dense foods could impair cognitive functions and induces anxiety and depressive-like behaviours in mice.

In this study, Ribeiro and colleagues have investigated how changes in diet-dependent microbiota and its metabolites could impact adult neurogenesis, revealing a mitochondria-dependent pathway as a novel mediator of this process.

Microbiota composition is highly dynamic and sensitive to nutritional factors, environment and lifecycle. For these reasons, microbial metabolism adjusts to surrounding fluctuations, leading to different bacterial products such as short-chain fatty acids (SCFA). SCFAs include propionate, butyrate and acetate, which control mitochondrial biogenesis and bioenergetics.

Neurogenesis in adult mammalian occurs in a mitochondria-dependent manner in two niches, the sub-ventricular zone (SVZ) and the sub-granular zone (SGZ) of the hippocampus, where neural stem cells (NSCs) self-renew, proliferate and differentiate into various type of neural cells. Mitochondrial metabolism finely tunes this process, increasing the production of reactive oxygen species (ROS) and oxidative metabolism during differentiation in response to higher cellular energetic demands, and promoting transcription of neurogenic genes.

To explore the relationship between diet-dependent gut microbiota and adult neurogenesis, mice fed with high fat, choline deficient (HFCD) diet for 14 and 24 weeks were used.

Results showed that dietary changes induced alterations in NSC dynamics and metabolic syndrome in mice, which trigger proliferation and premature neuronal differentiation in both adult niches, leading to exhaustion of the NSC pool and impairment of neurogenesis. Moreover, it has been shown that gut dysbiosis induced by diet associates with SCFAs metabolic pathways as butyrate and propionate, and these metabolites could induce alterations in mitochondrial biogenesis and oxidative stress, increasing mt-DNA copy number, mitochondrial ROS production and the number of mitochondria in NSCs. Therefore, in these contexts, NCSs may be further exposed to elevated ROS levels and triggered to a premature differentiation.

These data demonstrate a molecular link between diet, gut dysbiosis and adult neurogenesis. HFCD mice display increased cell death and oxidative stress in different brain regions, increased levels of pro-inflammatory cytokines and inhibition of hippocampal neurogenesis with memory impairment and depressive-like behavior. Moreover, the production of SCFAs like propionate and butyrate lead to an increase of mitochondrial biogenesis and ROS production, that can promote premature differentiation of NSCs, exhausting the NSC pool. Taken together, these findings add novel understandings of gut-brain axis role in adult neurogenesis and highlights a mitochondrial stress-dependent pathway as a key mediator in this crosstalk.

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