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- Rode, Julia, 1992-, et al.
(författare)
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Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses Toward an Emotional Task in Healthy Subjects : A Randomized Clinical Trial
- 2022
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Ingår i: Frontiers in nutrition. - : Frontiers Media S.A.. - 2296-861X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence from preclinical studies suggests that probiotics affect brain function via the microbiome-gut-brain axis, but evidence in humans remains limited.Objective: The present proof-of-concept study investigated if a probiotic product containing a mixture of Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 (in total 3 × 109 CFU/day) affected functional brain responses in healthy subjects during an emotional attention task.Design: In this double-blinded, randomized, placebo-controlled crossover study (Clinicaltrials.gov, NCT03615651), 22 healthy subjects (24.2 ± 3.4 years, 6 males/16 females) were exposed to a probiotic intervention and a placebo for 4 weeks each, separated by a 4-week washout period. Subjects underwent functional magnetic resonance imaging while performing an emotional attention task after each intervention period. Differential brain activity and functional connectivity were assessed.Results: Altered brain responses were observed in brain regions implicated in emotional, cognitive and face processing. Increased activation in the orbitofrontal cortex, a region that receives extensive sensory input and in turn projects to regions implicated in emotional processing, was found after probiotic intervention compared to placebo using a cluster-based analysis of functionally defined areas. Significantly reduced task-related functional connectivity was observed after the probiotic intervention compared to placebo. Fecal microbiota composition was not majorly affected by probiotic intervention.Conclusion: The probiotic intervention resulted in subtly altered brain activity and functional connectivity in healthy subjects performing an emotional task without major effects on the fecal microbiota composition. This indicates that the probiotic effects occurred via microbe-host interactions on other levels. Further analysis of signaling molecules could give possible insights into the modes of action of the probiotic intervention on the gut-brain axis in general and brain function specifically. The presented findings further support the growing consensus that probiotic supplementation influences brain function and emotional regulation, even in healthy subjects. Future studies including patients with altered emotional processing, such as anxiety or depression symptoms are of great interest.Clinical Trial Registration: [http://clinicaltrials.gov/], identifier [NCT03615651].
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| 4. |
- Edebol Carlman, Hanna M. T., et al.
(författare)
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Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses to an Arithmetic Stress Task in Healthy Subjects : A Randomised Clinical Trial and Proof-of-Concept Study
- 2022
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- Probiotics are suggested to impact physiological and psychological stress responses by acting on the gut-brain axis. We investigated if a probiotic product containing Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 affected stress processing in a double-blinded, randomised, placebo-controlled, crossover proof-of-concept study (NCT03615651). Twenty-two healthy subjects (24.2 ± 3.4 years, 6 men/16 women) underwent a probiotic and placebo intervention for 4 weeks each, separated by a 4-week washout period. Subjects were examined by functional magnetic resonance imaging while performing the Montreal Imaging Stress Task (MIST) as well as an autonomic nervous system function assessment during the Stroop task. Reduced activation in regions of the lateral orbital and ventral cingulate gyri was observed after probiotic intervention compared to placebo. Significantly increased functional connectivity was found between the upper limbic region and medioventral area. Interestingly, probiotic intervention seemed to predominantly affect the initial stress response. Salivary cortisol secretion during the task was not altered. Probiotic intervention did not affect cognitive performance and autonomic nervous system function during Stroop. The probiotic intervention was able to subtly alter brain activity and functional connectivity in regions known to regulate emotion and stress responses. These findings support the potential of probiotics as a non-pharmaceutical treatment modality for stress-related disorders.
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| 7. |
- Holster, Savanne, et al.
(författare)
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Faecal microbiota transfer in patients with microscopic colitis : a pilot study in collagenous colitis
- 2020
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 55:12, s. 1454-1466
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of patients with the aim to restore a disturbed gut microbiota. Methods: In this pilot study (NCT03275467), the effect of three repeated FMTs (day 0, two weeks, four weeks) was studied and followed up for six months in nine collagenous colitis (CC) patients, using two stool donors. Results: Five patients had an active disease at the time of baseline sampling. The primary endpoint (remission at six weeks, defined as <3 stools whereof <1 watery stool per day) was achieved by two of these patients, and by one at eight weeks. Overall, in all nine patients, FMT did not result in a significant reduction of watery stools, assessed by daily diary. However, diarrhoea (assessed by gastrointestinal symptom rating scale) was significantly improved at four (p = .038) and eight weeks (p = .038), indigestion at eight (p = .045) and 12 weeks (p = .006), disease-related worries at four (p = .027) and eight weeks (p = .027), and quality of life at six months (p = .009). FMT resulted in an increased number of lamina propria lymphocytes, possibly indicating an initial mucosal immune activation. No serious adverse events, no systemic effects, and no changes in faecal calprotectin and psychological symptoms were observed. Conclusions: FMT is able to improve symptoms in a yet undefined subset of CC patients. Further studies could help to characterise this subset and to understand if these results can be generalised to all microscopic colitis patients.
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- Rode, Julia, 1992-, et al.
(författare)
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Butyrate Rescues Oxidative Stress-Induced Transport Deficits of Tryptophan : Potential Implication in Affective or Gut-Brain Axis Disorders.
- 2021
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Ingår i: Neuropsychobiology. - : S. Karger. - 0302-282X .- 1423-0224. ; 80, s. 253-263
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Butyrate is a short-chain fatty acid metabolite produced by microbiota in the colon. With its antioxidant properties, butyrate has also been shown to alter the neurological functions in affective disorder models, suggesting it as a key mediator in gut-brain interactions.OBJECTIVE: Here, we evaluated the negative effect of oxidative stress on the transport of the serotonin precursor tryptophan as present in affective disorders. Butyrate was hypothesized to be able to rescue these deficits due to its antioxidative capacities and its effect on transmembrane transport of tryptophan. Human skin-derived fibroblasts were used as cellular models to address these objectives.METHODS: Human fibroblasts were treated with hydrogen peroxide to induce oxidative stress. Stressed as well as control cells were treated with different concentrations of butyrate. Tryptophan (3H) was used as a tracer to measure the transport of tryptophan across the cell membranes (n = 6). Furthermore, gene expression profiles of different amino acid transporters were analyzed (n = 2).RESULTS: As hypothesized,oxidative stress significantly decreased the uptake of tryptophan in fibroblast cells, while butyrate counteracted this effect. Oxidative stress did not alter the gene expression profile of amino acid transporters. However, treatment of stressed and control cells with different concentrations of butyrate differentially regulated the gene expression of large amino acid transporters 1 and 2, which are the major transporters of tryptophan.CONCLUSIONS: Gut microbiota-derived butyrate may have therapeutic potential in affective disorders characterized by either aberrant serotonergic activity or neuroinflammation due to its role in rescuing the oxidative stress-induced perturbations of tryptophan transport.
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| 10. |
- Rode, Julia, 1992-
(författare)
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Gut microbiota, its modifications and the gut-brain axis
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The human intestinal microbiota has a major impact on host physiology and might play an important role in several diseases. Therapeutic interventions aimed at modifying the gut microbiota might exert their effects locally as well as systemically, for example via the gut-brain axis, a bidirectional communication system.The overall aim of this thesis was to investigate potential modes of action via which modifications of the gut microbiota might influence health and disease. Paper I shows that faecal microbiota transfer could improve gastrointestinal symptoms in a subset of patients with collagenous colitis– a chronic low-grade inflammation of the large intestine. Papers II – IV describe the effects of an oral probiotic intervention on different aspects of the gut-brain axis in young, healthy adults. Paper II shows that brainactivity and functional connectivity during negative emotional stimuli were altered after probiotic intervention without major effects on the gut microbiota composition itself. Paper III shows that brain response patterns to an acute stressor were altered, whereas cortisol stress response, autonomic nervous system function and cognitive performance were not affected by the probiotic intervention. Paper IV describes the effect of the probiotic intervention on mental health in daily life. Amongst others, altered resting state brain function, slight improvements in depression symptoms and sleep quality were observed. Furthermore, serum levels of serotonin were slightly altered, indicating a potential mechanism of how probiotics might affect brain function. Paper V is an in vitro study that aimed to further elucidate a potential mechanism behind the microbiota-gut-brain axis. The short-chain fatty acid butyrate, an important microbial metabolite, rescued the disturbed uptake of the serotonin precursor tryptophan into fibroblasts mimicking cells of the nervous system.This thesis provides insights into whether and how gut microbiota modifications could improve health by affecting the gut-brain axis. Uncovering the underlying mechanisms might facilitate the development of personalised medicine.
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