Gut microbiota transplantation drives the adoptive transfer of colonic genotype-phenotype characteristics between mice lacking catestatin and their wild type counterparts

The gut microbiota is in continuous interaction with the intestinal mucosa via metabolic, neuro-immunological, and neuroendocrine pathways. Disruption in levels of antimicrobial peptides produced by the enteroendocrine cells, such as catestatin, has been associated with changes in the gut microbiota and imbalance in intestinal homeostasis. However, whether the changes in the gut microbiota have a causational role in intestinal dyshomeostasis has remained elusive. To this end, we performed reciprocal fecal microbial transplantation in wild-type mice and mice with a knockout in the catestatin coding region of the chromogranin-A gene (CST-KO mice). Combined microbiota phylogenetic profiling, RNA sequencing, and transmission electron microscopy were employed. Fecal microbiota transplantation from mice deficient in catestatin (CST-KO) to microbiota-depleted wild-type mice induced transcriptional and physiological features characteristic of a distorted colon in the recipient animals, including impairment in tight junctions, as well as an increased collagen area fraction indicating colonic fibrosis. In contrast, fecal microbiota transplantation from wild-type mice to microbiota-depleted CST-KO mice reduced collagen fibrotic area, restored disrupted tight junction morphology, and altered fatty acid metabolism in recipient CST-KO mice. This study provides a comprehensive overview of the murine metabolic- and immune-related cellular pathways and processes that are co-mediated by the fecal microbiota transplantation and supports a prominent role for the gut microbiota in the colonic distortion associated with the lack of catestatin in mice. Overall, the data show that the gut microbiota may play a causal role in the development of features of intestinal inflammation and metabolic disorders, known to be associated with altered levels of catestatin and may, thus, provide a tractable target in the treatment and prevention of these disorders

Is the High Probability of Type II Error an Issue in Error Awareness ERP Studies?

When researchers began addressing the electrophysiology of conscious error awareness more than a decade ago, the role of the error-related negativity (ERN), alongside the subsequently occurring error positivity (Pe), was an obvious locus of attention given the fact that they are taken as indices of cortical error processing. In contrast to the clear-cut findings that link the amplitude of the Pe to error awareness, the association between the ERN amplitude and error awareness is vastly unclear, with a range of studies reporting significant differences in the ERN amplitude with respect to error awareness, while others observing no modulation of the ERN amplitude. One problem in the studies obtaining null findings is the fact that conclusions are drawn based on small sample sizes, increasing the probability of type II error, especially given the fact that the ERN elicited using various error awareness paradigms tends to be small. The aim of the present study was to therefore address the issue of type II error in order to draw more certain conclusions about the modulation of the ERN amplitude by conscious error awareness. Forty participants performed a manual response inhibition task optimised to examine error awareness. While the early and late Pe amplitudes showed the expected sensitivity to error awareness, the ERN results depicted a more complex picture. The ERN amplitude for unaware errors appeared more negative than that of aware errors, both numerically and on the grand average ERP. The unexpected findings were explained in terms of (a) latency issues in the present data, (b) characteristics of the manual response inhibition task used and the possibility that it elicits variation in neurocognitive processing, and (c), in relation to possible contamination by the contingent negative variation (CNV), an ERP component elicited during response preparation. Suggestions for future research on how to address the issues raised in the present paper are also discussed

The ‘microbiota-gut-brain axis’ – between hype and revolution?

status: publishe

Short chain fatty acids: The microbiome’s route to the brain?

status: publishe

Nourishing the gut microbiota: The potential of prebiotics in microbiota-gut-brain axis research

Dietary fiber and prebiotics consistently modulate microbiota composition and function and hence may constitute a powerful tool in microbiota-gut-brain axis research. However, this is largely ignored in Hooks et al.’s analysis, which highlights the limitations of probiotics in establishing microbiome-mediated effects on neurobehavioural functioning and neglects discussing the potential of prebiotics in warranting the microbiota’s role in such effects.status: Published onlin

The role of short-chain fatty acids (SCFAs) in regulating stress responses, eating behavior, and nutritional state in anorexia nervosa: protocol for a randomized controlled trial

Abstract Objective This protocol proposes investigating the effects of short-chain fatty acids (SCFAs)—namely acetate, propionate, and butyrate—as mediators of microbiota-gut-brain interactions on the acute stress response, eating behavior, and nutritional state in malnourished patients with anorexia nervosa (AN). SCFAs are produced by bacterial fermentation of dietary fiber in the gut and have recently been proposed as crucial mediators of the gut microbiota's effects on the host. Emerging evidence suggests that SCFAs impact human psychobiology through endocrine, neural, and immune pathways and may regulate stress responses and eating behavior. Method We will conduct a randomized, triple-blind, placebo-controlled trial in 92 patients with AN. Patients will receive either a placebo or a mixture of SCFAs (acetate propionate, butyrate) using pH-dependent colon-delivery capsules for six weeks. This clinical trial is an add-on to the standard inpatient psychotherapeutic program focusing on nutritional rehabilitation. Hypotheses We hypothesize that colonic SCFAs delivery will modulate neuroendocrine, cardiovascular, and subjective responses to an acute laboratory psychosocial stress task. As secondary outcome measures, we will assess alterations in restrictive eating behavior and nutritional status, as reflected by changes in body mass index. Additionally, we will explore changes in microbiota composition, gastrointestinal symptoms, eating disorder psychopathology, and related comorbidities. Discussion The findings of this study would enhance our understanding of how gut microbiota-affiliated metabolites, particularly SCFAs, impact the stress response and eating behavior of individuals with AN. It has the potential to provide essential insights into the complex interplay between the gut, stress system, and eating behavior and facilitate new therapeutic targets for stress-related psychiatric disorders. This protocol is prospectively registered with ClinicalTrials.gov, with trial registration number NCT06064201

LaBGAS General Info

General info for LaBGAS members & friend

Catestatin selects for colonization of antimicrobial-resistant gut bacterial communities

The gut microbiota is in continuous interaction with the innermost layer of the gut, namely the epithelium. One of the various functions of the gut epithelium, is to keep the microbes at bay to avoid overstimulation of the underlying mucosa immune cells. To do so, the gut epithelia secrete a variety of antimicrobial peptides, such as chromogranin A (CgA) peptide catestatin (CST: hCgA352-372). As a defense mechanism, gut microbes have evolved antimicrobial resistance mechanisms to counteract the killing effect of the secreted peptides. To this end, we treated wild-type mice and CST knockout (CST-KO) mice (where only the 63 nucleotides encoding CST have been deleted) with CST for 15 consecutive days. CST treatment was associated with a shift in the diversity and composition of the microbiota in the CST-KO mice. This effect was less prominent in WT mice. Levels of the microbiota-produced short-chain fatty acids, in particular, butyrate and acetate were significantly increased in CST-treated CST-KO mice but not the WT group. Both CST-treated CST-KO and WT mice showed a significant increase in microbiota-harboring phosphoethanolamine transferase-encoding genes, which facilitate their antimicrobial resistance. Finally, we show that CST was degraded by Escherichia coli via an omptin-protease and that the abundance of this gene was significantly higher in metagenomic datasets collected from patients with Crohn's disease but not with ulcerative colitis. Overall, this study illustrates how the endogenous antimicrobial peptide, CST, shapes the microbiota composition in the gut and primes further research to uncover the role of bacterial resistance to CST in disease states such as inflammatory bowel disease

Laboratory for Brain-Gut Axis Studies

Interdisciplinary lab of microbiota-gut-brain axis research enthusiasts headed by Prof. Lukas Van Oudenhov

The EAT–Lancet reference diet and cognitive function across the life course

The EAT–Lancet Commission devised a sustainable reference diet with the aim of reducing the incidence of non-communicable diseases and mortality globally while improving food system sustainability. The extent to which the reference diet supports cognitive function across the life course, however, has not yet been evaluated. This Review assesses the evidence for diet supporting cognitive function from childhood into old age. A comprehensive but non-exhaustive literature search was done, synthesising studies that investigated the effect of whole foods on cognition in healthy, community-dwelling human participants. We found that the current evidence base is weak with mixed conclusions and multiple methodological caveats, which precludes strong conclusions pertaining to the suitability of dietary recommendations for each food group per age group. Long-term intervention and prospective cohort studies are needed to reduce this knowledge deficit. Revising dietary recommendations with the aim of maintaining an adequate nutrient intake to sustain healthy cognitive function across the life course could be worthwhile. This Review outlines recommendations for future work to help improve the current knowledge deficit regarding dietary intake and cognitive function across the life course and its implications for dietary guidelines such as the EAT–Lancet Commission