Neurobiological effects of food fermentation-derived metabolites for metabolic and mental health

Carey, Nathan

Neurobiological effects of food fermentation-derived metabolites for metabolic and mental health

cbnd

Date

2023

Authors

Carey, Nathan

Publisher

University College Cork

Abstract

Nutrition and diet are becoming increasingly popular therapeutic interventions as we discover more about the complex roles the foods we consume play in maintaining our health status. It is now clear that foods we ingest daily and their metabolites interact with systems both within and outside the gastrointestinal tract including the gut microbiome, the nervous system, immune system and hormonal system. Each of these play essential roles in the bi-directional communication pathway of the microbiota-gut-brain axis. Interactions between our food and this axis can potentially influence centrally mediated processes such as cognition, mood and even appetite. While several foods have been identified as being beneficial to our health, there is one food group that remains under investigated and holds promise as a reservoir of both beneficial bacteria and bioactive compounds – fermented foods. Fermented foods are created through the controlled enzymatic conversion of foods to simpler organics substances by microorganisms. Common examples include foods like kimchi (a fermented cabbage product), kefir (a fermented milk product) and kombucha (a fermented sweet tea beverage). While human studies on fermented foods remain sparce, one recent finding recorded lower perceived stress in human adults who underwent a dietary intervention that included fermented food intake. Recent findings in rodents suggest that fermented foods can alter social behaviour, reduce body weight and lead to reduced anxiety in animals. The mechanism by which fermented foods act is still unknown but it likely due to a number of factors such as their probiotic bacteria content, their metabolite content including short chain fatty acids (SCFA), and the ability to breakdown their starter compounds into simpler molecules and increase their bioavailability such as phenolic compounds in fruits and vegetables. The research conducted in this thesis aims to investigate the ability of food-fermentation derived metabolites, with a specific focus on SCFAs and polyphenols, to alter the neurobiological functions associated with central appetite regulation (hypothalamus) and cognition (hippocampus). Using in vitro assays, we tested the selected panel of metabolites shown to be found in fermented foods, and capable of crossing the blood brain barrier, on both immortal cell lines (hypothalamic and hippocampal) and on primary neurosphere cultures (hippocampal). A panel of SCFA were administered to hippocampal and hypothalamic cell lines and were capable of altering brain-derived neurotrophic factor (BDNF) gene expression. These metabolites were also tested on primary hippocampal cells using a neurosphere assay of proliferation. Positive trends were observed across many of the treatments, however these trends were not significant. Perhaps most interesting were our findings when submitting the same hippocampal neurosphere assay to a panel of phenolic compounds. Apigenin and kaempferol (both flavonoids) significantly increased hippocampal cell proliferation. Moreover, to enhance the efficiency of data analysis, a semi-automatic quantification pipeline was developed for high-throughput screening of primary neurosphere cultures. This pipeline offers a systematic and reliable method for evaluating neurosphere proliferation, providing a valuable tool for future studies in the field. Our results highlight the modulatory effects of SCFA and phenolic compounds on hypothalamic and hippocampal cells in vitro, emphasising the potential role of dietary metabolites and fermented foods as a whole on brain function related to metabolic and mental health. These findings also highlight the need for more in depth analysis of fermented foods and their neuromodulator effects both in vivo.

Description

Controlled Access

Keywords

Neuroscience , Food fermentation , Metabolits , Neurospheres

Citation

Carey, N. 2023. Neurobiological effects of food fermentation-derived metabolites for metabolic and mental health. MSc Thesis, University College Cork.