Periodic Reporting for period 2 - MoodBugs (How our gut microbes influence how we feel – bacterial metabolites and inflammation as mediators of human microbiota-affect relationships)
Okres sprawozdawczy: 2023-03-01 do 2024-08-31
Do our gut microbes influence our emotions? This sounded far-fetched a decade ago, but rodent research has shown that
the microbial ecosystem in the gut (the gut microbiota) causally impacts affective processes. The underlying microbiota-gut-brain
signalling mechanisms include the capacity of the microbiota to produce short-chain fatty acids (SCFA) from dietary
fiber and to regulate inflammation.
These rodent findings have great potential to identify new modifiable players in the (patho)physiology of affective processes
and disorders, which is urgently needed given the stalled revolution in affective science, but human translation is needed to
fulfill this potential.
MoodBugs aims to fill this gap by investigating the relationship between the gut microbiota and stress sensitivity and fear
learning, two affective endophenotypes, and the microbiota-gut-brain (SCFA, inflammation) and neur(ochemic)al
mechanisms underlying it, in an interdisciplinary hypothesis-driven fashion.
In a population-based study, my team showed a cross-sectional association beteen a specific microbiota profile (B2
enterotype) and mental well-being. To test directionality of this association, I propose a longitudinal and mechanistic
population-based study [WP1]. To test causality, I will study the effect of depleting the gut microbiota using an antibiotic
intervention on stress responses, fear learning and their brain basis [WP2].
In a placebo-controlled trial, I showed that SCFA administration (1 week) attenuates the cortisol response to psychosocial
stress. To test for whom and how SCFA work, I will investigate microbiota composition as a predictor of response to SCFA,
and gene expression in affective circuits as the neural mechanism mediating their effect [WP3]. I will induce systemic
inflammation to test its causal effect on stress and fear, and on neuroinflammation in the underlying neural circuitry as
hypothesized mediator. I will also test the potential of SCFA to dampen these inflammation-induced effects [WP4].
the microbial ecosystem in the gut (the gut microbiota) causally impacts affective processes. The underlying microbiota-gut-brain
signalling mechanisms include the capacity of the microbiota to produce short-chain fatty acids (SCFA) from dietary
fiber and to regulate inflammation.
These rodent findings have great potential to identify new modifiable players in the (patho)physiology of affective processes
and disorders, which is urgently needed given the stalled revolution in affective science, but human translation is needed to
fulfill this potential.
MoodBugs aims to fill this gap by investigating the relationship between the gut microbiota and stress sensitivity and fear
learning, two affective endophenotypes, and the microbiota-gut-brain (SCFA, inflammation) and neur(ochemic)al
mechanisms underlying it, in an interdisciplinary hypothesis-driven fashion.
In a population-based study, my team showed a cross-sectional association beteen a specific microbiota profile (B2
enterotype) and mental well-being. To test directionality of this association, I propose a longitudinal and mechanistic
population-based study [WP1]. To test causality, I will study the effect of depleting the gut microbiota using an antibiotic
intervention on stress responses, fear learning and their brain basis [WP2].
In a placebo-controlled trial, I showed that SCFA administration (1 week) attenuates the cortisol response to psychosocial
stress. To test for whom and how SCFA work, I will investigate microbiota composition as a predictor of response to SCFA,
and gene expression in affective circuits as the neural mechanism mediating their effect [WP3]. I will induce systemic
inflammation to test its causal effect on stress and fear, and on neuroinflammation in the underlying neural circuitry as
hypothesized mediator. I will also test the potential of SCFA to dampen these inflammation-induced effects [WP4].
Work Package 1: Data collection for this work package began on the 31st of October 2022 and so far, 106 of the foreseen 240 participants have started the study, and 60 have completed the longitudinal follow-up (6 months).
Work Package 2: Data collection has started on the 19th of January 2023. Currently, 40 out of the foreseen participants have completed the study.
Work Package 3:
For WP 3.1 data collection has been finished, and all samples have been analysed (n=220). Data analysis is currently ongoing, part of the results have been presented in abstract form, and submission of the full paper is planned for Q4 of 2024.
For WP. 3.2 the files have been submitted to all relevant instances (including the Federal Agency for Nuclear Control since this involves a new radiotracer) in April 2024, we expect approval in Q2 2024 and start of data collection in Q3 2024.
Work Package 4:
For WP 4.1 data collection will start on May 7th 2024.
For WP 4.2 files for submission to the relevant instances are currently being prepared, with approval expected in Q3 2024 and start of data collection in Q4 2024.
Work Package 2: Data collection has started on the 19th of January 2023. Currently, 40 out of the foreseen participants have completed the study.
Work Package 3:
For WP 3.1 data collection has been finished, and all samples have been analysed (n=220). Data analysis is currently ongoing, part of the results have been presented in abstract form, and submission of the full paper is planned for Q4 of 2024.
For WP. 3.2 the files have been submitted to all relevant instances (including the Federal Agency for Nuclear Control since this involves a new radiotracer) in April 2024, we expect approval in Q2 2024 and start of data collection in Q3 2024.
Work Package 4:
For WP 4.1 data collection will start on May 7th 2024.
For WP 4.2 files for submission to the relevant instances are currently being prepared, with approval expected in Q3 2024 and start of data collection in Q4 2024.