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Thunberg, P., Reingardt, M., Rode, J. & Msghina, M. (2024). Categorical and dimensional aspects of stimulant medication effects in adult patients with ADHD and healthy controls. Frontiers in Pharmacology, 15, Article ID 1412178.
Åpne denne publikasjonen i ny fane eller vindu >>Categorical and dimensional aspects of stimulant medication effects in adult patients with ADHD and healthy controls
2024 (engelsk)Inngår i: Frontiers in Pharmacology, E-ISSN 1663-9812, Vol. 15, artikkel-id 1412178Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Psychiatric disorders are categorized on the basis of presence and absence of diagnostic criteria using classification systems such as the international classification of diseases (ICD) and the diagnostic and statistical manual for mental disorders (DSM). The research domain criteria (RDoC) initiative provides an alternative dimensional framework for conceptualizing mental disorders. In the present paper, we studied neural and behavioral effects of central stimulant (CS) medication in adults with attention deficit hyperactivity disorder (ADHD) and healthy controls using categorical and dimensional stratifications. AX-Continuous Performance Task (AX-CPT) was utilized for the later purpose, and participants were classified as "reactive" or "proactive" based on their baseline proactive behavioral index (PBI). Out of the 65 individuals who participated (33 healthy controls and 32 patients with ADHD), 53 were included in the final analysis that consisted of 31 healthy controls and 22 ADHD patients. For the dimensional stratification, a median split of PBI scores divided participants into "reactive" and "proactive" groups irrespective of whether they had ADHD or not. Participants performed AX-CPT in conjunction with functional magnetic resonance imaging (fMRI) before and after CS medication. We found no significant within or between group CS effect when participants were categorically assigned as healthy controls and ADHD patients. For the dimensional stratification, however, CS selectively increased activation in frontoparietal cognitive areas and induced a shift towards proactive control mode in the reactive group, without significantly affecting the proactive group. In conclusion, the neural and behavioral effects of CS were more clear-cut when participants were stratified into dimensional groups rather than diagnostic categories.

sted, utgiver, år, opplag, sider
Frontiers Media S.A., 2024
Emneord
cognitive control, central stimulants, ADHD, AX-CPT, proactive behavioral index
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-115210 (URN)10.3389/fphar.2024.1412178 (DOI)001274860000001 ()39050752 (PubMedID)2-s2.0-85199411820 (Scopus ID)
Forskningsfinansiär
Nyckelfonden, OLL 935421Region Örebro County, OLL 973230
Tilgjengelig fra: 2024-08-03 Laget: 2024-08-03 Sist oppdatert: 2024-08-15bibliografisk kontrollert
Vumma, R., Rode, J., Yang, L., Montero, J., König, J., Wall, R., . . . Rangel, I. (2024). Exploring Therapeutic Strategies for Neuropsychiatric Disorders: Modulating Inflammation, Gut-Brain Interactions, and the Role of Butyrate. Paper presented at ASPET 2024 Annual Meeting - Neuropharmacology, Arlington, VA, USA, May 16-19, 2024.. Journal of Pharmacology and Experimental Therapeutics, 387(S3), Article ID 336.127906.
Åpne denne publikasjonen i ny fane eller vindu >>Exploring Therapeutic Strategies for Neuropsychiatric Disorders: Modulating Inflammation, Gut-Brain Interactions, and the Role of Butyrate
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2024 (engelsk)Inngår i: Journal of Pharmacology and Experimental Therapeutics, ISSN 0022-3565, E-ISSN 1521-0103, Vol. 387, nr S3, artikkel-id 336.127906Artikkel i tidsskrift, Meeting abstract (Fagfellevurdert) Published
sted, utgiver, år, opplag, sider
American Society for Pharmacology and Experimental, 2024
Emneord
Neuropsychiatric Disorders
HSV kategori
Forskningsprogram
Psykiatri
Identifikatorer
urn:nbn:se:oru:diva-114769 (URN)10.1124/jpet.336.127906 (DOI)
Konferanse
ASPET 2024 Annual Meeting - Neuropharmacology, Arlington, VA, USA, May 16-19, 2024.
Tilgjengelig fra: 2024-07-12 Laget: 2024-07-12 Sist oppdatert: 2024-08-28bibliografisk kontrollert
Rode, J., Brengesjö Johnson, L., König, J., Rangel, I., Engstrand, L., Repsilber, D. & Brummer, R. J. (2024). Fecal samples and rectal swabs adequately reflect the human colonic luminal microbiota. Gut microbes, 16(1), Article ID 2416912.
Åpne denne publikasjonen i ny fane eller vindu >>Fecal samples and rectal swabs adequately reflect the human colonic luminal microbiota
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2024 (engelsk)Inngår i: Gut microbes, ISSN 1949-0976, E-ISSN 1949-0984, Vol. 16, nr 1, artikkel-id 2416912Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The appropriateness of the fecal microbiota to adequately reflect the gut microbiota composition from more difficult to access luminal content at different colonic locations has been debated. Here, in a healthy population, luminal samples were collected from terminal ileum to rectum using an unique sampling technique without the need of prior bowel cleansing/preparation. Rectal swabs were collected immediately prior colonoscopy by an experienced physician, and fecal samples were collected at home by the participants themselves. Microbiota composition was evaluated as relative abundance, α-diversity and Bray-Curtis dissimilarities. Our data suggest that fecal samples and rectal swabs present noninvasive, easily accessible, low-cost sampling tools that are accurate proxies to characterize luminal large intestinal microbiota composition.

sted, utgiver, år, opplag, sider
Taylor & Francis, 2024
Emneord
Gut microbiota, aspiration, feces, gut microbiome, intraluminal, rectal, sampling technique
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-117026 (URN)10.1080/19490976.2024.2416912 (DOI)001339702800001 ()39439236 (PubMedID)2-s2.0-85207174680 (Scopus ID)
Forskningsfinansiär
Swedish Research Council, 20230004-H-01
Tilgjengelig fra: 2024-10-24 Laget: 2024-10-24 Sist oppdatert: 2025-02-11bibliografisk kontrollert
Tingö, L., Bergh, C., Rode, J., Roca Rubio, M. F., Persson, J., Brengesjö Johnson, L., . . . Hutchinson, A. (2024). The effect of whole-diet interventions on memory and cognitive function in healthy older adults: a systematic review. Advances in nutrition (Bethesda, Md.), 15(9), Article ID 100291.
Åpne denne publikasjonen i ny fane eller vindu >>The effect of whole-diet interventions on memory and cognitive function in healthy older adults: a systematic review
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2024 (engelsk)Inngår i: Advances in nutrition (Bethesda, Md.), ISSN 2161-8313, Vol. 15, nr 9, artikkel-id 100291Artikkel, forskningsoversikt (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: An increasing number of cross-sectional studies suggests that diet may impact memory and cognition in healthy older adults. However, randomized, controlled trials investigating the effects of whole-diet interventions on memory and cognition in healthy older adults are rather rare and conflicting results are often reported.

OBJECTIVE: Therefore, a systematic review was conducted to compile the current evidence regarding the potential effects of whole-diet interventions on 1) memory and, 2) other cognitive outcomes in older adults.

METHODS: Studies that reported on randomized, controlled trials with dietary interventions in healthy older adults (60 yrs. and older) were included. Studies utilizing supplements, single food items or trials in specific patient groups (ie neurodegenerative diagnoses) were excluded.

RESULTS: For the 23 included articles, the main outcomes examined fell into one or more of the following categories: cognitive task-based outcomes related to memory, other cognitive task-based outcomes, and additional outcomes related to cognitive function or disease risk. Three of the studies that investigated dietary interventions alone and two multi-domain study showed positive effects on memory function, whereas five multi-domain interventions and one intervention that focused on diet alone showed positive effects on other cognitive outcomes.

CONCLUSIONS: The effect of randomized, controlled whole-diet interventions on memory and cognitive function in healthy older adults is modest and inconclusive, highlighting the need for more well-designed, sufficiently powered studies. Furthermore, the potential mechanisms by which diet impacts cognition in healthy aging need to be elucidated.

REGISTRY AND REGISTRY NUMBER FOR SYSTEMATIC REVIEWS OR META-ANALYSES: This systematic review is registered in PROSPERO under ID CRD42022329759.

sted, utgiver, år, opplag, sider
Oxford University Press, 2024
Emneord
cognitive decline, diet, elderly, memory, nutrition, prevention
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-115530 (URN)10.1016/j.advnut.2024.100291 (DOI)001309135400001 ()39154864 (PubMedID)2-s2.0-85202915953 (Scopus ID)
Tilgjengelig fra: 2024-08-21 Laget: 2024-08-21 Sist oppdatert: 2024-11-05bibliografisk kontrollert
Forsgård, R. A., Rode, J., Lobenius Palmér, K., Kamm, A., Patil, S., Tacken, M. G. J., . . . Brummer, R. J. (2023). Limosilactobacillus reuteri DSM 17938 supplementation and SARS-CoV-2 specific antibody response in healthy adults: a randomized, triple-blinded, placebo-controlled trial. Gut microbes, 15(1), Article ID 2229938.
Åpne denne publikasjonen i ny fane eller vindu >>Limosilactobacillus reuteri DSM 17938 supplementation and SARS-CoV-2 specific antibody response in healthy adults: a randomized, triple-blinded, placebo-controlled trial
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2023 (engelsk)Inngår i: Gut microbes, ISSN 1949-0976, E-ISSN 1949-0984, Vol. 15, nr 1, artikkel-id 2229938Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Studies have shown that probiotics can decrease the symptoms of respiratory tract infections as well as increase antibody responses following certain vaccinations. We examined the effect of probiotic supplementation on anti-SARS-CoV-2 specific antibody responses upon SARS-CoV-2 infection as well as after COVID-19 vaccination. In this randomized, triple-blinded, placebo-controlled intervention study with a parallel design, 159 healthy adults without prior SARS-CoV-2 infection or COVID-19 vaccination and any known risk factors for severe COVID-19 were randomly allocated into two study arms. The active treatment arm consumed a probiotic product containing a minimum of 1 × 108 colony-forming units of Limosilactobacillus reuteri DSM 17938 + 10 μg vitamin D3 twice daily for 6 months. The placebo arm consumed identical tablets containing only 10 μg vitamin D3. Anti-SARS-CoV-2 specific antibodies and virus neutralizing antibody titers were analyzed from blood samples collected at baseline, after 3 months, and after 6 months. Differences in serum antibody titers between the two study arms were tested with independent t-test using log-transformed values. In the intention-to-treat (ITT) analysis, SARS-CoV-2 infected individuals in the active treatment arm (n = 6) tended to have higher serum anti-spike IgG (609 [168-1480] BAU/ml vs 111 [36.1-1210] BAU/ml, p = 0.080) and anti-receptor binding domain (RBD) IgG (928 [212-3449] BAU/ml vs (83.7 [22.8-2094] BAU/ml, p = 0.066) levels than individuals in the placebo arm (n = 6). Considering individuals who were fully vaccinated with mRNA-based COVID-19 vaccines, the active treatment arm (n = 10) exhibited significantly higher serum levels of anti-RBD IgA (135 [32.9-976] BAU/ml vs 61.3 [26.7-97.1] BAU/ml, p = 0.036) than the placebo arm (n = 7) >28 days postvaccination. Supplementation with specific probiotics might improve the long-term efficacy of mRNA-based COVID-19 vaccines via enhanced IgA response.

sted, utgiver, år, opplag, sider
Taylor & Francis, 2023
Emneord
COVID-19, Probiotics, SARS-CoV-2, antibody, immunology
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-106943 (URN)10.1080/19490976.2023.2229938 (DOI)001020016900001 ()37401761 (PubMedID)2-s2.0-85164011823 (Scopus ID)
Tilgjengelig fra: 2023-07-05 Laget: 2023-07-05 Sist oppdatert: 2023-08-01bibliografisk kontrollert
Rode, J., Runnamo, R., Thunberg, P. & Msghina, M. (2023). Salience and hedonic experience as predictors of central stimulant treatment response in ADHD: A resting state fMRI study. Journal of Psychiatric Research, 163, 378-385
Åpne denne publikasjonen i ny fane eller vindu >>Salience and hedonic experience as predictors of central stimulant treatment response in ADHD: A resting state fMRI study
2023 (engelsk)Inngår i: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 163, s. 378-385Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: Roughly 20-30% of patients with Attention-deficit/hyperactivity disorder (ADHD) fail to respond to central stimulant (CS) medication. Genetic, neuroimaging, biochemical and behavioral biomarkers for CS response have been investigated, but currently there are no biomarkers available for clinical use that help identify CS responders and non-responders.

METHODS: In the present paper, we studied if incentive salience and hedonic experience evaluated after a single-dose CS medication could predict response and non-response to CS medication. We used a bipolar visual analogue 'wanting' and 'liking' scale to gauge incentive salience and hedonic experience in 25 healthy controls (HC) and 29 ADHD patients. HC received 30 mg methylphenidate (MPH) and ADHD patients received either MPH or lisdexamphetamine (LDX) as selected by their clinician, with dosage individually determined for optimal effect. Clinician-evaluated global impression - severity (CGI-S) and improvement (CGI-I) and patient-evaluated improvement (PGI-I) were used to assess response to CS medication. Resting state functional magnetic resonance imaging (fMRI) was conducted before and after single-dose CS to correlate wanting and liking scores to changes in functional connectivity.

RESULTS: Roughly 20% of the ADHD patients were CS non-responders (5 of 29). CS responders had significantly higher incentive salience and hedonic experience scores compared to healthy controls and CS non-responders. Resting state fMRI showed that wanting scores were significantly associated to changes in functional connectivity in ventral striatum including nucleus accumbens.

CONCLUSION: Incentive salience and hedonic experience evaluated after a single-dose CS medication segregate CS responders and non-responders, with corresponding neuroimaging biomarkers in the brain reward system.

sted, utgiver, år, opplag, sider
Elsevier, 2023
Emneord
Attention-deficit/hyperactivity disorder, Central stimulant treatment, Incentive salience, Pharmacological challenge, Resting state, Treatment prediction
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-106174 (URN)10.1016/j.jpsychires.2023.05.073 (DOI)001013035000001 ()37269772 (PubMedID)2-s2.0-85160538869 (Scopus ID)
Forskningsfinansiär
Nyckelfonden, 93542Region Örebro County, OLL-787911
Tilgjengelig fra: 2023-06-05 Laget: 2023-06-05 Sist oppdatert: 2024-01-02bibliografisk kontrollert
Rode, J., Edebol Carlman, H. M. T., König, J., Hutchinson, A., Thunberg, P., Persson, J. & Brummer, R. J. (2022). Multi-Strain Probiotic Mixture Affects Brain Morphology and Resting State Brain Function in Healthy Subjects: An RCT. Cells, 11(18), Article ID 2922.
Åpne denne publikasjonen i ny fane eller vindu >>Multi-Strain Probiotic Mixture Affects Brain Morphology and Resting State Brain Function in Healthy Subjects: An RCT
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2022 (engelsk)Inngår i: Cells, E-ISSN 2073-4409, Vol. 11, nr 18, artikkel-id 2922Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Probiotics can alter brain function via the gut-brain axis. We investigated the effect of a probiotic mixture containing Bifidobacterium longum, Lactobacillus helveticus and Lactiplantibacillus plantarum. In a randomized, placebo-controlled, double-blinded crossover design, 22 healthy subjects (6 m/16 f; 24.2 ± 3.4 years) underwent four-week intervention periods with probiotics and placebo, separated by a four-week washout period. Voxel-based morphometry indicated that the probiotic intervention affected the gray matter volume of a cluster covering the left supramarginal gyrus and superior parietal lobule (p < 0.0001), two regions that were also among those with an altered resting state functional connectivity. Probiotic intervention resulted in significant (FDR < 0.05) functional connectivity changes between regions within the default mode, salience, frontoparietal as well as the language network and several regions located outside these networks. Psychological symptoms trended towards improvement after probiotic intervention, i.e., the total score of the Hospital Anxiety and Depression Scale (p = 0.056) and its depression sub-score (p = 0.093), as well as sleep patterns (p = 0.058). The probiotic intervention evoked distinct changes in brain morphology and resting state brain function alongside slight improvements of psycho(bio)logical markers of the gut-brain axis. The combination of those parameters may provide new insights into the modes of action by which gut microbiota can affect gut-brain communication and hence brain function.

sted, utgiver, år, opplag, sider
MDPI, 2022
Emneord
CO2 inhalation challenge, autonomic nervous system, brain-derived neurotrophic factor (BDNF), cortisol awakening response, gut microbiota, mental health, resting state functional connectivity, serotonin, sleep quality, structural changes
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-101446 (URN)10.3390/cells11182922 (DOI)000858164900001 ()36139496 (PubMedID)2-s2.0-85138356660 (Scopus ID)
Merknad

Funding agencies:

Global Medical Innovation

Pfizer Consumer Healthcare

General Electric 20150081

Tilgjengelig fra: 2022-09-24 Laget: 2022-09-24 Sist oppdatert: 2022-10-05bibliografisk kontrollert
Edebol Carlman, H. M. T., Rode, J., König, J., Repsilber, D., Hutchinson, A., Thunberg, P., . . . Brummer, R. J. (2022). 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. Nutrients, 14(7), Article ID 1329.
Åpne denne publikasjonen i ny fane eller vindu >>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
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2022 (engelsk)Inngår i: Nutrients, E-ISSN 2072-6643, Vol. 14, nr 7, artikkel-id 1329Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
MDPI, 2022
Emneord
Montreal Imaging Stress Task (MIST), autonomic nervous system, brain activity, functional magnetic resonance imaging (fMRI), gut microbiota, gut-brain axis
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-98559 (URN)10.3390/nu14071329 (DOI)000781150400001 ()35405944 (PubMedID)2-s2.0-85126989886 (Scopus ID)
Merknad

Funding agencies:

Global Medical Innovation

Pfizer Consumer Healthcare

General Electric 20150081

Tilgjengelig fra: 2022-04-13 Laget: 2022-04-13 Sist oppdatert: 2025-02-11bibliografisk kontrollert
Rode, J., Edebol Carlman, H. M. T., König, J., Repsilber, D., Hutchinson, A., Thunberg, P., . . . Brummer, R. J. (2022). Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses Toward an Emotional Task in Healthy Subjects: A Randomized Clinical Trial. Frontiers in nutrition, 9, Article ID 827182.
Åpne denne publikasjonen i ny fane eller vindu >>Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses Toward an Emotional Task in Healthy Subjects: A Randomized Clinical Trial
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2022 (engelsk)Inngår i: Frontiers in nutrition, E-ISSN 2296-861X, Vol. 9, artikkel-id 827182Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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].

sted, utgiver, år, opplag, sider
Frontiers Media S.A., 2022
Emneord
Brain activity, emotional attention task (EAT), functional connectivity, functional magnetic resonance imaging (fMRI), gut microbiota, gut-brain axis, probiotics, task-related
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-99027 (URN)10.3389/fnut.2022.827182 (DOI)000796705800001 ()35571902 (PubMedID)2-s2.0-85130241273 (Scopus ID)
Merknad

Funding agencies:

Global Medical Innovation 

Pfizer Consumer Healthcare 

General Electric

Tilgjengelig fra: 2022-05-17 Laget: 2022-05-17 Sist oppdatert: 2025-02-11bibliografisk kontrollert
Rode, J., Yang, L., König, J., Hutchinson, A., Wall, R., Venizelos, N., . . . Vumma, R. (2021). Butyrate Rescues Oxidative Stress-Induced Transport Deficits of Tryptophan: Potential Implication in Affective or Gut-Brain Axis Disorders. Neuropsychobiology, 80(3), 253-263
Åpne denne publikasjonen i ny fane eller vindu >>Butyrate Rescues Oxidative Stress-Induced Transport Deficits of Tryptophan: Potential Implication in Affective or Gut-Brain Axis Disorders
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2021 (engelsk)Inngår i: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 80, nr 3, s. 253-263Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
S. Karger, 2021
Emneord
Affective disorders, Butyrate, Gut-brain interactions, Oxidative stress, Tryptophan transport
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-86759 (URN)10.1159/000510886 (DOI)000657413400006 ()33075780 (PubMedID)2-s2.0-85094634419 (Scopus ID)
Tilgjengelig fra: 2020-10-23 Laget: 2020-10-23 Sist oppdatert: 2022-09-12bibliografisk kontrollert
Organisasjoner
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0001-9402-4756