Saffron extract interferes with lipopolysaccharide-induced brain activation of the kynurenine pathway and impairment of monoamine neurotransmission in mice

BackgroundAlthough activation of inflammatory processes is essential to fight infections, its prolonged impact on brain function is well known to contribute to the pathophysiology of many medical conditions, including neuropsychiatric disorders. Therefore, identifying novel strategies to selectively counter the harmful effects of neuroinflammation appears as a major health concern. In that context, this study aimed to test the relevance of a nutritional intervention with saffron, a spice known for centuries for its beneficial effect on health.MethodsFor this purpose, the impact of an acute oral administration of a standardized saffron extract, which was previously shown to display neuromodulatory properties and reduce depressive-like behavior, was measured in mice challenged with lipopolysaccharide (LPS, 830 μg/kg, ip).ResultsPretreatment with saffron extract (6.5 mg/kg, per os) did not reduce LPS-induced sickness behavior, preserving therefore this adaptive behavioral response essential for host defense. However, it interfered with delayed changes of expression of cytokines, chemokines and markers of microglial activation measured 24 h post-LPS treatment in key brain areas for behavior and mood control (frontal cortex, hippocampus, striatum). Importantly, this pretreatment also counteracted by that time the impact of LPS on several neurobiological processes contributing to inflammation-induced emotional alterations, in particular the activation of the kynurenine pathway, assessed through the expression of its main enzymes, as well as concomitant impairment of serotonergic and dopaminergic neurotransmission.ConclusionAltogether, this study provides important clues on how saffron extract interferes with brain function in conditions of immune stimulation and supports the relevance of saffron-based nutritional interventions to improve the management of inflammation-related comorbidities

Microbiota and Metabolite Profiling as Markers of Mood Disorders: A Cross-Sectional Study in Obese Patients

Obesity is associated with an increased risk of several neurological and psychiatric diseases, but few studies report the contribution of biological features in the occurrence of mood disorders in obese patients. The aim of the study is to evaluate the potential links between serum metabolomics and gut microbiome, and mood disturbances in a cohort of obese patients. Psychological, biological characteristics and nutritional habits were evaluated in 94 obese subjects from the Food4Gut study stratified according to their mood score assessed by the Positive and Negative Affect Schedule (PANAS). The fecal gut microbiota and plasma non-targeted metabolomics were analysed. Obese subjects with increased negative mood display elevated levels of Coprococcus as well as decreased levels of Sutterella and Lactobacillus. Serum metabolite profile analysis reveals in these subjects altered levels of several amino acid-derived metabolites, such as an increased level of L-histidine and a decreased in phenylacetylglutamine, linked to altered gut microbiota composition and function rather than to differences in dietary amino acid intake. Regarding clinical profile, we did not observe any differences between both groups. Our results reveal new microbiota-derived metabolites that characterize the alterations of mood in obese subjects, thereby allowing to propose new targets to tackle mood disturbances in this context. Food4gut, clinicaltrial.gov: NCT03852069

Gut microbiota, biological and psychological alterations in alcohol use disorder

Alcohol use disorder (AUD) is a major public health problem affecting 5 to 10% of the population. Chronic alcohol abuse induces alterations in the composition of the gut microbiota, which are correlated with psychological symptoms, suggesting the involvement of the gut-brain axis in the development of addiction. Among dietary component able to modulate the microbiota, dietary fibers are of particular interest. In a first study we investigated the link between dietary fiber intake and psychological symptoms in AUD patients. We found that only a proportion of AUD patients displays alterations in the gut microbiota composition. This dysbiosis is associated with higher craving scores and impaired sociability. Finally, our intervention study aiming to supplement AUD patients with inulin shows that 1) it does not lead to gastro-intestinal intolerance, 2) it induces specific changes in the gut microbiota, 3) it has limited impact on biological and behavioural outcomes, 4) it increases sociability score. If our results show the importance of prebiotic dietary fiber in AUD patients, further studies are needed to define an adapted strategy targeting the gut microbiota to improve metabolic and behavioural alterations in these patients.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 202

Improving the acceptability to enhance the efficiency of stroke rehabilitation procedures based on brain-computer interfaces: General public results

International audienceStroke leaves around 40% of surviving patients dependent in their activities of daily living, notably due to severe motor disabilities [Inserm, 2019]. Brain-Computer Interfaces (BCIs) have been shown to be efficient for improving motor recovery after stroke [Cervera et al., 2018], but this efficiency is still far from the level required to achieve the clinical breakthrough expected by both clinicians and patients. While technical levers of improvement have been identified, they are insufficient: fully optimised BCIs are pointless if patients and clinicians do not want to use them [Blain-Moraes et al., 2012].We hypothesise that improving BCI acceptability and acceptance, by better informing stakeholders about BCI functioning and by personalising the BCI-based rehabilitation procedures to each patient, respectively, will favour engagement in the rehabilitation process and result in an increased efficiency.Our first objective was to identify the factors influencing the intention to use (IU) BCIs [Davis, 1989]. Based on the literature, we constructed a model of BCI acceptability and adapted it in questionnaires addressed to the general population (n=753) and post-stroke patients (n=33). Videos were included, one about the general functioning of BCIs, the second about their relevance for rehabilitation.We used random forest algorithms to explain IU based on our model's factors. After the first video, IU was mainly explained by subjective and personal factors, i.e., perceived usefulness (PU), perceived ease of use (PEOU) and BCI playfulness for the general population, and PU, autonomy and engagement in the rehabilitation for the patients. After the second video, the explanatory factors became more scientific/rational, with PU, cost-benefits ratio and scientific relevance for the general population, and PU, scientific relevance and ease of learning for patients.The shift of main explanatory factors (before/after second video) from subjective representations to scientific arguments highlights the impact of providing patients with clear information regarding BCIs

Improving the acceptability to enhance the efficiency of stroke rehabilitation procedures based on brain-computer interfaces: General public results

International audienceStroke leaves around 40% of surviving patients dependent in their activities of daily living, notably due to severe motor disabilities [Inserm, 2019]. Brain-Computer Interfaces (BCIs) have been shown to be efficient for improving motor recovery after stroke [Cervera et al., 2018], but this efficiency is still far from the level required to achieve the clinical breakthrough expected by both clinicians and patients. While technical levers of improvement have been identified, they are insufficient: fully optimised BCIs are pointless if patients and clinicians do not want to use them [Blain-Moraes et al., 2012].We hypothesise that improving BCI acceptability and acceptance, by better informing stakeholders about BCI functioning and by personalising the BCI-based rehabilitation procedures to each patient, respectively, will favour engagement in the rehabilitation process and result in an increased efficiency.Our first objective was to identify the factors influencing the intention to use (IU) BCIs [Davis, 1989]. Based on the literature, we constructed a model of BCI acceptability and adapted it in questionnaires addressed to the general population (n=753) and post-stroke patients (n=33). Videos were included, one about the general functioning of BCIs, the second about their relevance for rehabilitation.We used random forest algorithms to explain IU based on our model's factors. After the first video, IU was mainly explained by subjective and personal factors, i.e., perceived usefulness (PU), perceived ease of use (PEOU) and BCI playfulness for the general population, and PU, autonomy and engagement in the rehabilitation for the patients. After the second video, the explanatory factors became more scientific/rational, with PU, cost-benefits ratio and scientific relevance for the general population, and PU, scientific relevance and ease of learning for patients.The shift of main explanatory factors (before/after second video) from subjective representations to scientific arguments highlights the impact of providing patients with clear information regarding BCIs

[What is the role of the gut microbiota in the development of alcohol use disorders?]

Alcohol addiction is a complex and multifactorial disease influenced by social, psychological and biological aspects. The current pharmacological drugs used in the management of alcohol dependence have shown only a modest efficacy and the relapse rate remains high in this disease. Recently, the gut microbiota, a huge and dynamic ecosystem made up of billions of microorganisms living in our intestine, has been shown to regulate many important functions for human health. Indeed, the gut microbiota is known to influence our metabolism, our immune system as well as our nervous system with consequences for brain functions, mood and behaviour. We have shown that heavy and chronic alcohol consumption induced important changes in the composition of the gut microbiota. Furthermore, the microbial changes are associated with the severity of depression, anxiety and alcohol craving that are important factors predicting the risk of relapse. This suggests the existence of a gut-brain axis in alcohol dependence and supports the development of new therapeutic alternatives, targeting the gut microbiota, in the management of alcohol dependence

Modelling the Acceptance of BCI-based Stroke Rehabilitation Procedures: Heading for Efficiently Personalised Therapies

International audienc

Troubles liés à l’usage d’alcool : et si l’addiction trouvait son origine dans l’intestin ?

L’addiction à l’alcool est une maladie complexe, impliquant à la fois des facteurs sociaux, psychologiques et biologiques. La prise en charge des patients alcoolo-dépendants est difficile car les médicaments actuels ont une efficacité limitée dans le maintien de l’abstinence, et le taux de rechute reste très élevé. Récemment, le microbiote intestinal, un écosystème constitué de milliards de micro-organismes vivant dans notre intestin, est devenu un acteur clé de la santé humaine. Il est connu pour réguler notre métabolisme, notre système immunitaire, mais également notre système nerveux, et donc notre comportement et notre humeur. Nos études récentes ont montré que la consommation abusive d’alcool entraîne des modifications importantes de la composition du microbiote intestinal. Nous avons également montré que ces altérations microbiennes étaient associées à la sévérité des symptômes de dépression, d’anxiété et d’appétence à l’alcool, suggérant ainsi l’existence d’un dialogue entre l’intestin et le cerveau. Ces résultats encouragent la recherche de nouvelles pistes thérapeutiques, ciblant le microbiote intestinal, dans le traitement de la dépendance à l’alcool.[What is the role of the gut microbiota in the development of alcohol use disorders?]. Alcohol addiction is a complex and multifactorial disease influenced by social, psychological and biological aspects. The current pharmacological drugs used in the management of alcohol dependence have shown only a modest efficacy and the relapse rate remains high in this disease. Recently, the gut microbiota, a huge and dynamic ecosystem made up of billions of microorganisms living in our intestine, has been shown to regulate many important functions for human health. Indeed, the gut microbiota is known to influence our metabolism, our immune system as well as our nervous system with consequences for brain functions, mood and behaviour. We have shown that heavy and chronic alcohol consumption induced important changes in the composition of the gut microbiota. Furthermore, the microbial changes are associated with the severity of depression, anxiety and alcohol craving that are important factors predicting the risk of relapse. This suggests the existence of a gut-brain axis in alcohol dependence and supports the development of new therapeutic alternatives, targeting the gut microbiota, in the management of alcohol dependence

Which factors affect patients' acceptability of BCIs for functional rehabilitation after stroke? A questionnaire study among 140 patients and a comparison with the general public

International audienceAlthough motor imagery-based BCIs have been demonstrated to be relevant for improving motor recovery after stroke, they remain barely used in rehabilitation services. We hypothesise that acceptability (assessed in terms of perceived usefulness (PU), ease of use (PEOU) and behavioural intention (BI)) could serve as a lever for fostering the adoption of BCIs through the improvement of their efficacy. More precisely, we suggest that improving BCIs acceptability could alleviate post-stroke patients’ anxiety, stimulate their engagement in the BCI process, and thereby, favour skill acquisition (self-regulation abilities), which will have positive effects on motor recovery.We created a model of acceptability of BCIs for functional rehabilitation after stroke, and designed an associated questionnaire that we used to empirically assess the weight each factor of the model had on acceptability. We obtained 140 responses from post-stroke patients, and compared them with data collected in the general public (N=753) by using T-tests, χ² tests and regressions.Results showed that patients and general public have high acceptability levels (BI: 8.48/10 and 8.23/10, respectively; PU: 8.34/10 and 8.28/10, respectively), but PEOU was significantly lower in patients (6.43/10 and 7.17/10). For both, PU, scientific relevance and ease of learning were the most influential acceptability factors. Nonetheless, the perceived benefits on risk balance is more positive for the patients than it is for the general public; patients also consider that their close relatives will be more in favour of BCI rehabilitation; in addition, patients want human guidance when using a BCI, whereas the general public prefer a computerised help system.Globally, results highlight the importance of better informing on the scientific evidence related to BCIs and of personalising rehabilitation procedures to facilitate learning. One next step will consist in applying this approach with clinicians

Which factors affect patients' acceptability of BCIs for functional rehabilitation after stroke? A questionnaire study among 140 patients and a comparison with the general public

International audienceAlthough motor imagery-based BCIs have been demonstrated to be relevant for improving motor recovery after stroke, they remain barely used in rehabilitation services. We hypothesise that acceptability (assessed in terms of perceived usefulness (PU), ease of use (PEOU) and behavioural intention (BI)) could serve as a lever for fostering the adoption of BCIs through the improvement of their efficacy. More precisely, we suggest that improving BCIs acceptability could alleviate post-stroke patients’ anxiety, stimulate their engagement in the BCI process, and thereby, favour skill acquisition (self-regulation abilities), which will have positive effects on motor recovery.We created a model of acceptability of BCIs for functional rehabilitation after stroke, and designed an associated questionnaire that we used to empirically assess the weight each factor of the model had on acceptability. We obtained 140 responses from post-stroke patients, and compared them with data collected in the general public (N=753) by using T-tests, χ² tests and regressions.Results showed that patients and general public have high acceptability levels (BI: 8.48/10 and 8.23/10, respectively; PU: 8.34/10 and 8.28/10, respectively), but PEOU was significantly lower in patients (6.43/10 and 7.17/10). For both, PU, scientific relevance and ease of learning were the most influential acceptability factors. Nonetheless, the perceived benefits on risk balance is more positive for the patients than it is for the general public; patients also consider that their close relatives will be more in favour of BCI rehabilitation; in addition, patients want human guidance when using a BCI, whereas the general public prefer a computerised help system.Globally, results highlight the importance of better informing on the scientific evidence related to BCIs and of personalising rehabilitation procedures to facilitate learning. One next step will consist in applying this approach with clinicians