Periodic Reporting for period 2 - GutBrainGABA (Mapping the impact of gut microbiota on brain and behaviour through the lens of GABA)
Periodo di rendicontazione: 2022-03-01 al 2023-08-31
Human beings are over 99% genetically identical. It seems striking therefore, that 1% of this genetic difference accounts for the large extent of individual variations seen in human behaviour and brain function. One promising alternative source of individual differences is the resident bacteria in the gastrointestinal tract,which is 40-90% distinct between different individuals. Bacteria in the human gut outnumber human cells, and account for nearly 10 times as much DNA as that from human cells. Some gut bacteria have been shown to produce Gamma Amino Butyric Acid (GABA) and serotonin (5-HT), molecules that function as neurotransmitters in the human brain. However, it is not known whether their production in the gut has any impact on behavioural and brain function. This project focuses on GABA, a neurotransmitter that often serves as the 'brakes' in the communication between neurons.
The overall objective of the project is to test if GABA produced by bacteria in the gut can influence brain levels of GABA or behaviours that depend on GABA. If the project finds evidence to support this possibility it can open up a new frontier of research on how diet can influence brain functioning. At a more fundamental level, it can point to processes outside the brain through which brain levels of GABA are maintained.
The overall objective of the project is to test if GABA produced by bacteria in the gut can influence brain levels of GABA or behaviours that depend on GABA. If the project finds evidence to support this possibility it can open up a new frontier of research on how diet can influence brain functioning. At a more fundamental level, it can point to processes outside the brain through which brain levels of GABA are maintained.
The project has obtained full ethical approval from the university and the NHS UK ethics boards, and all experimental protocols have been extensively piloted and finalised. For the choice of the probiotic to be used in WP2, a number of commercially available probiotics were assessed for their ability to produce GABA under different laboratory conditions. This study identified one bacterial strain that produced significantly more GABA than all others, and accordingly this probiotic was chosen to be used in WP2. This laboratory study comparing different probiotics has been published in a peer-reviewed journal (Monteagudo-Mera et al., 2023).
Despite early delays due to the COVID pandemic, data collection for both work packages has been progressing steadily since March 2022. Since WP2 involves a double-blind cross-over trial, the results will be analysed only after the data collection has completed.
Despite early delays due to the COVID pandemic, data collection for both work packages has been progressing steadily since March 2022. Since WP2 involves a double-blind cross-over trial, the results will be analysed only after the data collection has completed.
The project identified an important role for the acidity of the environment in the production of GABA by the probiotic bacteria (Monteagudo-Mera et al., 2023). While this study was not part of the original set of planned outputs for the project, we realised that the results from a comparative assay of different commercially available probiotics, under different laboratory conditions, might be useful for the larger field of study.
The main results of the project will be analysed only after the data collection period is over, and test whether the abundance of bacteria capable of producing GABA can influence brain levels of GABA, which is measured through both direct brain based measures as well as more indirect behaviour-based measures.
The main results of the project will be analysed only after the data collection period is over, and test whether the abundance of bacteria capable of producing GABA can influence brain levels of GABA, which is measured through both direct brain based measures as well as more indirect behaviour-based measures.