Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

The microbiota-gut-brain (MGB) axis is a bidirectional communication system with multiple signaling routes between the microbiota, the gut and the brain. Evidence suggests that the gut and the brain can influence another, and the MGB axis is being investigated as a link between stress sensitivity and gastrointestinal disorders. An important signaling route of the MGB-axis is via the immune system, which can transmit inflammatory signals bidirectionally between the gut and the brain. This signaling route represents a potential mechanism through which stress-induced inflammation and gut inflammation may be linked, highlighting the intricate interplay between psychological stress, the immune system, and gut health. Although previous studies in specific populations have demonstrated a correlation between systemic inflammation and stress-related outcomes, evidence for an association in the general population remains limited. Given the increasing recognition of the importance of the MGB axis in mental health, the relationship between gut inflammation, systemic inflammation, and stress-related outcomes should be explored. The aim of this thesis was to investigate the association between gut and systemic inflammation with subjective stress, mood indices, and vagus nerve activity in the general population. A cross-sectional study was conducted and preliminary analyses included 37 participants (81.08% female) who were recruited between October 2022 and April 2023. Included participants had a mean age of 28.2 years (SD = 9.86), and a mean body mass index (BMI) of 23.9 kg/m2 (SD = 3.84). Stool samples were collected to measure fecal calprotectin levels as a marker of gut inflammation, while high-sensitive C-reactive protein (hs-CRP) was measured in serum as an indicator of systemic inflammation. Participants completed psychological questionnaires to evaluate subjective stress and affective states, and electrocardiogram (ECG) recordings were obtained to assess resting-state heart rate variability (HRV) as a measurement of vagus nerve activity. Simple linear regression and general linear models (GLM) were employed to assess the association between fecal calprotectin, hs-CRP and stress outcomes, including HRV and psychological questionnaires. Participants were grouped according to their fecal calprotectin level (below quantification (<4mg/kg), low (4-12 mg/kg), low-to-moderate (13-50 mg/kg)) and assessed for group differences in stress outcomes. Participants in the low-to-moderate fecal calprotectin group had higher hs-CRP levels compared to those in the low fecal calprotectin group (p = 0.0195), but caution is warranted, as the association may be BMI-dependent. We did not detect significant associations between hs-CRP and physiological questionnaires and we were unable to replicate previously established significant associations between hs-CRP levels and HRV indices. Participants in the low-to-moderate fecal calprotectin group had lower State-Trait Anxiety Inventory (STAI) state scores than participants in the low fecal calprotectin group (p = 0.0164). There was no significant association between fecal calprotectin and HRV indices. In conclusion, these findings suggest a complex relationship between gut and systemic inflammation, subjective stress, and vagus nerve activity in the general population. Further research is needed to confirm these preliminary findings and elucidate their underlying mechanisms.

Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

The global increase in depression represents a significant public health burden, emphasizing the need to identify modifiable risk factors for Major Depressive Disorder (MDD). Over the past two decades, evidence has suggested systemic inflammation as a potential risk factor. Crucially, gut inflammation and disruptions in gut microbiota composition have been shown to influence systemic inflammation. It is hypothesized that dietary interventions could positively impact this disruption and through the microbiota-gut-brain (MGB) axis impact depression-related-inflammation. However, results from previous studies investigating this relationship are inconsistent or may lack important mediators. Specifically, a fiber-rich diet may offer therapeutic benefits for depression by promoting the production of short-chain fatty acids (SCFAs), known for their anti-inflammatory properties. Therefore, this thesis aimed to explore the immune-modulating effects of dietary fiber on stress and affective state as an endophenotype for depression in the general population and the effect of putative mediators SCFAs, gut inflammation and systemic inflammation. A cross-sectional study involving 83 participants from the general Belgian population was conducted, utilizing the Perceived Stress Scale, 10-items (PSS-10), and momentary measures of stress, positive affect (PA), and negative affect (NA) as indicators of mental well-being. Serum hs-CRP levels served as a marker of systemic inflammation, while fecal calprotectin levels indicated gut inflammation. Daily dietary fiber intake was assessed using a Food Frequency Questionnaire (FFQ), and fecal SCFA levels were measured as a representative marker of colonic concentrations. Spearman correlations and mediation analysis were performed to assess direct and indirect effects. Our findings did not reveal significant associations between dietary fiber intake, stress and affective state, aligning with inconsistent findings in existing literature on this relationship. Interestingly, we observed a significant negative association between hs-CRP and acute momentary stress (p = 0.042) and NA (p < 0.0001). However, caution is needed in interpreting this result due to the absence of controlled confounders. Furthermore, mediation analysis did not identify significant indirect effects, but a direct negative effect of dietary fiber on momentary NA (95% CI [-0.50; -0.0031]). Future research should include taxonomic analyses of the microbiome and serum SCFAs with a larger sample size to deepen our understanding of the relationship between dietary fiber and depressive symptoms and possible mediators.

Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

Introduction: The gut microbiome has been identified as a key player in the gut-brain axis (GBA), affecting our psychological functioning, particularly stress sensitivity. To investigate this relationship, the gut microbiome can be manipulated, including with the aid of antibiotics such as rifaximin. Previous studies have demonstrated that rifaximin intervention reduces depressive-like behaviour in rats and mitigates psychological stress responses in a small number of healthy volunteers. However, most evidence about the microbiome GBA has been studied in rodents, with limited studies conducted in humans. Therefore, our study aims to investigate whether administering rifaximin can improve stress sensitivity in healthy men. Methods: Each participant was administered either 550 mg rifaximin or placebo twice daily for 2 weeks. All participants were subjected to the Maastricht Acute Stress Test (MAST) at preand post-intervention. Cardiovascular parameters, including systolic (SBP) and diastolic blood pressure (DBP), and pulse rate (PR) were measured at 12 time points before, during, and after the MAST, along with subjective stress responses using visual analogue scales (VAS) and State-Trait Anxiety inventory (STAI). The 12 time points were reduced to peak, peak-baseline, and peak-end for SBP, DBP, PR and VAS. High sensitive C-reactive protein (hs-CRP), a marker for inflammation, was measured at 4 time points before and after the MAST from which data was reduced to end-baseline. In addition to the primary endpoints, The root mean square of the successive differences (RMSSD) between heart rates was measured as an index for resting heart rate variability (HRV). Furthermore, emotional states were evaluated using affective questionnaires, including GAD-7, PHQ-9, PSS, GSRS, PANAS, LEIDS-R, and BFI10. Finally, macronutrient intake and the Bristol Stool Score (BSS) were assessed as well. Results: Group 1 consisted of 2 men whereas the median age was 32 and median BMI was 21.298, while Group 2 comprised 5 men whereas the median age was 22 and the median BMI was 22.635. In both groups, there was no significant difference observed in macronutrient intake, BSS, and affective questionnaires at post-intervention compared to pre-intervention. Resting HRV was increased at post-intervention compared to pre-intervention in Group 2, but without significant difference in both groups. In terms of the response to the MAST, only Group 2 exhibited reductions in peak (SBP), peak-baseline (SBP and DBP), and peak-end (SBP and DBP) at post-intervention compared to pre-intervention. However, none of the results were statistically significant. Furthermore, no significant difference in PR, subjective stress, and hsCRP was found in both groups at post-intervention compared to pre-intervention. Discussion: This study did not offer more insight into the relation between rifaximin intervention and stress sensitivity in healthy men as none of the parameters reported a significant difference at post-intervention. More work with a larger study population will need to be performed. Gut microbiome analysis and short-chain fatty acids measurements could provide more information about the mechanism of rifaximin-induced gut microbiota alterations on stress sensitivity. Other indicators to measure stress, such as brain activity, salivary cortisol, Interleukin-6, and HRV need to be taken into account in future research.

Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

According to the World Health Organization (WHO), 1 in 13 globally suffers from anxiety. Anxiety disorders are common and pervasive mental disorders, yet they are hard to treat. Lately, there has been a growing interest in the role of the microbiota-gut-brain axis in mental disorders, more specifically, in anxiety disorders. Alterations in the gut microbiota can exert influences on the gut-brain axis and one specific group of microbial metabolites, short chain fatty acids (SCFAs) are speculated to play a dominant role in this interaction. Thus, understanding these interactions may be of great importance regarding treatment and prevention. Over the past years, researches tried to manipulate mice in order to develop suitable models and make a translation to human research possible. However, the complexity of these interactions makes it very hard to translate these findings from mice to humans. This study aimed to answer the question if SCFAs could influence fear in humans. More specifically, we hypothesized a decrease in fear expression across conditioning, extinction, recall and renewal. Furthermore, we expected a decline in self-reported negative mood and distress. These hypotheses were tested in a double blind, randomized, placebo-controlled trial. A pre-posttest design with a one-week intervention of SCFAs was performed in three conditions (placebo, SCFA equivalent to 10gr of fiber, SCFAs equivalent to 20gr of fiber) during which participants adhered to a low-fiber diet. 66 healthy male participants were included in the study. The aim was to look at the physiological role of SCFAs by looking at the site of production, using colon delivery capsules. Participants engaged in a fear task on two test days, which measured fear processes such as acquisition, extinction learning, extinction recall and fear renewal. Negative mood and distress were assessed using self-reported questionnaires. Linear mixed models were used to examine if the intervention influenced the different phases and trials of fear learning across test days. Additionally, to investigate differences in subjective ratings of fear, participants’ affect ratings of the fear task were explored. This study found no evidence for the hypotheses that SCFAs can decrease fear reaction across acquisition, extinction learning, extinction recall and fear renewal in healthy humans. Furthermore, no evidence was found for a decline in self-reported mood and distress. However, translating animal models to human models is difficult for several reasons. With this study being one of the first making the translation to healthy humans, it offers useful insights for further research. Furthermore, research in animals proposed an important role for SCFAs in fear, suggesting that further research in humans should be considered.