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Background: Brainstem nuclei play a critical role in both ascending monoaminergic modulation of cortical function and arousal, and in descending bulbospinal pain modulation. Even though sex-related differences in the function of both systems have been reported in animal models, a complete understanding of sex differences, as well as menopausal effects, in brainstem connectivity in humans is lacking. This study evaluated resting-state connectivity of the dorsal raphe nucleus (DRN), right and left locus coeruleus complex (LCC), and periaqueductal gray (PAG) according to sex and menopausal status in healthy individuals. In addition, relationships between systemic estrogen levels and brainstem-network connectivity were examined in a subset of participants. Methods: Resting-state fMRI was performed in 50 healthy men (age, 31.2 ± 8.0 years), 53 healthy premenopausal women (age, 24.7 ± 7.3 years; 22 in the follicular phase, 31 in the luteal phase), and 20 postmenopausal women (age, 54.6 ± 7.2 years). Permutation Analysis of Linear Models (5000 permutations) was used to evaluate differences in brainstem-network connectivity according to sex and menopausal status, controlling for age. In 10 men and 17 women (9 premenopausal; 8 postmenopausal), estrogen and estrogen metabolite levels in plasma and stool were determined by liquid chromatography-mass spectrometry/mass spectrometry. Relationships between estrogen levels and brainstem-network connectivity were evaluated by partial least squares analysis. Results: Left LCC-executive control network (ECN) connectivity showed an overall sex difference (p = 0.02), with higher connectivity in women than in men; however, this was mainly due to differences between men and pre-menopausal women (p = 0.008). Additional sex differences were dependent on menopausal status: PAG-default mode network (DMN) connectivity was higher in postmenopausal women than in men (p = 0.04), and PAG-sensorimotor network (SMN) connectivity was higher in premenopausal women than in men (p = 0.03) and postmenopausal women (p = 0.007). Notably, higher free 2-hydroxyestrone levels in stool were associated with higher PAG-SMN and PAG-DMN connectivity in premenopausal women (p < 0.01). Conclusions: Healthy women show higher brainstem-network connectivity involved in cognitive control, sensorimotor function, and self-relevant processes than men, dependent on their menopausal status. Further, 2-hydroxyestrone, implicated in pain, may modulate PAG connectivity in premenopausal women. These findings may relate to differential vulnerabilities to chronic stress-sensitive disorders at different life stages.
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BACKGROUND: Neuropathic pain is a complex chronic condition resulting from the damage or dysfunction of the nervous system. Conventional therapies offer limited success and often come with various adverse effects. Therefore, the exploration of alternative therapies, such as phytoconstituents, may be of substantial interest for their potential to alleviate neuropathic pain. OBJECTIVES: This review systematically examines the diverse roles and mechanisms of various phytoconstituents in modulating neuropathic pain. In this study, a comprehensive analysis of phytoconstituents in neuropathic pain is carried out to understand their mechanism in preventing the disease. METHOD: The current search is done in the databases of Google Scholar, PubMed Central, ScienceDirect, and Scopus using the keywords: neuropathic pain, phytoconstituents as analgesics, physiological effects of medicinal plants, and natural products, to find the most relevant articles of the last 10 years. RESULT: Out of 125 articles, 112 were included in this study, which revealed that several phytoconstituents inhibit several biomarkers responsible for neuropathic pain. Moreover, this review highlights the underlying molecular pathways and targets through which these bioactive compounds exert their therapeutic effects, emphasizing their potential as novel pharmacological agents. CONCLUSION: This study concludes that phytoconstituents may possess potential applications in managing neuropathic pain and could be effectively used as an alternative approach to mitigate the condition with enhanced risk of safety and tolerability.
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Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic-associated fatty liver disease (MAFLD), is the most common liver disease worldwide. The progression to fibrosis, occurring against a backdrop of hepatic steatosis and inflammation, critically determines liver-related morbidity and mortality. Inflammatory processes contribute to various stages of MAFLD and thought to instigate hepatic fibrosis. For this reason, targeting inflammation has been heavily nominated as a strategy to mitigate liver fibrosis. Lipopolysaccharide binding protein (LBP) is a secreted protein that plays an established role in innate immune responses. Here, using adoptive transfer studies and tissue-specific deletion models we show that hepatocytes are the dominant contributors to circulating LBP. In a murine model of MAFLD, hepatocyte-specific deletion of LBP restrained hepatic inflammation and improved liver function abnormalities, but not measures of fibrosis. Human studies, including genetic evidence, corroborate an important role for LBP in hepatic inflammation with minimal impact on fibrosis. Collectively, our data argues against the idea that targeting hepatic inflammation is a viable approach to reducing fibrosis.
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Proteínas de Fase Aguda , Cirrose Hepática , Humanos , Cirrose Hepática/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/imunologia , Proteínas de Fase Aguda/metabolismo , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Inflamação/patologia , Inflamação/metabolismo , Fígado/patologia , Fígado/metabolismo , Fígado/imunologia , Animais , Camundongos , Masculino , Proteínas de TransporteRESUMO
Obesity and food addiction are associated with distinct brain signatures related to reward processing, and early life adversity (ELA) also increases alterations in these same reward regions. However, the neural mechanisms underlying the effect of early life adversity on food addiction are unknown. Therefore, the aim of this study was to examine the interactions between ELA, food addiction, and brain morphometry in individuals with obesity. 114 participants with high body mass index (BMI) underwent structural MRIs, and completed several questionnaires (e.g., Yale Food Addiction Scale (YFAS), Brief Resilience Scale (BRS), Early Traumatic Inventory (ETI)). Freesurfer 6 was applied to generate the morphometry of brain regions. A multivariate pattern analysis was used to derive brain morphometry patterns associated with food addiction. General linear modeling and mediation analyses were conducted to examine the effects of ELA and resilience on food addiction in individuals with obesity. Statistical significance was determined at a level of p < 0.05. High levels of ELA showed a strong association between reward control brain signatures and food addiction (p = 0.03). Resilience positively mediated the effect of ELA on food addiction (B = 0.02, p = 0.038). Our findings suggest that food addiction is associated with brain signatures in motivation and reward processing regions indicative of dopaminergic dysregulation and inhibition of cognitive control regions. These mechanistic variabilities along with early life adversity suggest increased vulnerability to develop food addiction and obesity in adulthood, which can buffer by the neuroprotective effects of resilience, highlighting the value of incorporating cognitive appraisal into obesity therapeutic regimens.
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Índice de Massa Corporal , Encéfalo , Dependência de Alimentos , Imageamento por Ressonância Magnética , Obesidade , Humanos , Feminino , Masculino , Dependência de Alimentos/psicologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Adulto , Obesidade/psicologia , Obesidade/patologia , Experiências Adversas da Infância/psicologia , Recompensa , Adulto Jovem , Pessoa de Meia-Idade , Inquéritos e Questionários , Resiliência PsicológicaRESUMO
BACKGROUND & AIMS: Adverse childhood experiences (ACE) are associated with increased risk of irritable bowel syndrome (IBS), a female-predominant chronic abdominal disorder. Factors contributing to this association have not been well-studied. We compared sex differences in ACE for adults with and without IBS and evaluated the impact of anxiety and resilience on the relationship between ACE and IBS. METHODS: Sex and disease differences in total score and ACE subtypes from the ACE Questionnaire in subjects with IBS and control subjects were assessed. Cross-sectional mediation analysis determined if anxiety (Hospital Anxiety and Depression Scale) and resilience (Connor-Davidson Resilience Scale or Brief Resilience Scale) mediated the relationship between ACE and IBS. RESULTS: Of 798 participants studied, 368 met IBS diagnostic criteria (265 women, 103 men) and 430 were healthy control subjects (277 women, 153 men). Prevalence and number of ACE were higher in IBS versus control subjects (P < .001) but similar between IBS women and men. Household mental illness increased odds of having IBS in women (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.35-2.85; false discovery rate [FDR], 0.002) and men (OR, 2.32; 95% CI, 1.26-4.33; FDR, 0.014). Emotional abuse increased odds of having IBS in women (OR, 1.94; 95% CI, 1.23-3.09; FDR, 0.019) and sexual abuse increased odds of IBS in men (OR, 3.54; 95% CI, 1.35-10.38; FDR, 0.027). Anxiety mediated 54% (P < .001) of ACE's effect on IBS risk and resilience mediated 12%-14% (Connor-Davidson Resilience Scale, P = .008; Brief Resilience Scale, P = .018). CONCLUSIONS: Both men and women with a history of ACE are twice as likely to have IBS than those without an ACE. Anxiety mediated the relationship between ACE and IBS in men and women and resilience mediated this relationship only in women.
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Importance: Perceived social isolation is associated with negative health outcomes, including increased risk for altered eating behaviors, obesity, and psychological symptoms. However, the underlying neural mechanisms of these pathways are unknown. Objective: To investigate the association of perceived social isolation with brain reactivity to food cues, altered eating behaviors, obesity, and mental health symptoms. Design, Setting, and Participants: This cross-sectional, single-center study recruited healthy, premenopausal female participants from the Los Angeles, California, community from September 7, 2021, through February 27, 2023. Exposure: Participants underwent functional magnetic resonance imaging while performing a food cue viewing task. Main Outcomes and Measures: The main outcomes included brain reactivity to food cues, body composition, self-reported eating behaviors (food cravings, reward-based eating, food addiction, and maladaptive eating behaviors), and mental health symptoms (anxiety, depression, positive and negative affect, and psychological resilience). Results: The study included 93 participants (mean [SD] age, 25.38 [7.07] years). Participants with higher perceived social isolation reported higher fat mass percentage, lower diet quality, increased maladaptive eating behaviors (cravings, reward-based eating, uncontrolled eating, and food addiction), and poor mental health (anxiety, depression, and psychological resilience). In whole-brain comparisons, the higher social isolation group showed altered brain reactivity to food cues in regions of the default mode, executive control, and visual attention networks. Isolation-related neural changes in response to sweet foods correlated with various altered eating behaviors and psychological symptoms. These altered brain responses mediated the connection between social isolation and maladaptive eating behaviors (ß for indirect effect, 0.111; 95% CI, 0.013-0.210; P = .03), increased body fat composition (ß, -0.141; 95% CI, -0.260 to -0.021; P = .02), and diminished positive affect (ß, -0.089; 95% CI, -0.188 to 0.011; P = .09). Conclusions and Relevance: These findings suggest that social isolation is associated with altered neural reactivity to food cues within specific brain regions responsible for processing internal appetite-related states and compromised executive control and attentional bias and motivation toward external food cues. These neural responses toward specific foods were associated with an increased risk for higher body fat composition, worsened maladaptive eating behaviors, and compromised mental health. These findings underscore the need for holistic mind-body-directed interventions that may mitigate the adverse health consequences of social isolation.
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Sinais (Psicologia) , Saúde Mental , Feminino , Humanos , Adulto , Estudos Transversais , Encéfalo/diagnóstico por imagem , Isolamento Social , Comportamento Alimentar , ObesidadeRESUMO
BACKGROUND: Chronic pain affects nearly 20% of the U.S. POPULATION: It is a leading cause of disability globally and is associated with a heightened risk for suicide. The role of the central nervous system in the perception and maintenance of chronic pain has recently been accepted, but specific brain circuitries involved have yet to be mapped across pain types in a large-scale study. METHODS: We used data from the UK Biobank (N = 21,968) to investigate brain structural alterations in individuals reporting chronic pain compared with pain-free control participants and their mediating effect on history of suicide attempt. RESULTS: Chronic pain and, more notably, chronic multisite pain was associated with, on average, lower surface area throughout the cortex after adjusting for demographic, clinical, and neuropsychiatric confounds. Only participants with abdominal pain showed lower subcortical volumes, including the amygdala and brainstem, and lower cerebellum volumes. Participants with chronic headaches showed a widespread thicker cortex compared with control participants. Mediation analyses revealed that precuneus thickness mediated the relationship of chronic multisite pain and history of suicide attempt. Mediating effects were also identified specific to localized pain, with the strongest effect being amygdala volume in individuals with chronic abdominal pain. CONCLUSIONS: Results support a widespread effect of chronic pain on brain structure and distinct brain structures underlying chronic musculoskeletal pain, visceral pain, and headaches. Mediation effects of regions in the extended ventromedial prefrontal cortex subsystem suggest that exacerbated negative internal states, negative self-referencing, and impairments in future planning may underlie suicidal behaviors in individuals with chronic pain.
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Dor Crônica , Tentativa de Suicídio , Humanos , Tentativa de Suicídio/psicologia , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Dor AbdominalRESUMO
BACKGROUND & AIMS: Low adherence to Mediterranean diet (MD) has been shown to be associated with a higher prevalence of irritable bowel syndrome (IBS), but its association with IBS symptoms is not established. We aim to assess the association between MD and IBS symptoms, identify components of MD associated with IBS symptoms, and determine if a symptom-modified MD is associated with changes in the gut microbiome. METHODS: One hundred and six Rome +IBS and 108 health control participants completed diet history and gastrointestinal symptom questionnaires. Adherence to MD was measured using Alternate Mediterranean Diet and Mediterranean Diet Adherence Screener. Sparse partial least squares analysis identified MD food items associated with IBS symptoms. Stool samples were collected for 16S ribosomal RNA gene sequencing and microbial composition analysis in IBS subjects. RESULTS: Alternate Mediterranean Diet and Mediterranean Diet Adherence Screener scores were similar between IBS and health control subjects and did not correlate with Irritable Bowel Syndrome Severity Scoring System, abdominal pain, or bloating. Among IBS participants, a higher consumption of fruits, vegetables, sugar, and butter was associated with a greater severity of IBS symptoms. Multivariate analysis identified several MD foods to be associated with increased IBS symptoms. A higher adherence to symptom-modified MD was associated with a lower abundance of potentially harmful Faecalitalea, Streptococcus, and Intestinibacter, and higher abundance of potentially beneficial Holdemanella from the Firmicutes phylum. CONCLUSIONS: A standard MD was not associated with IBS symptom severity, although certain MD foods were associated with increased IBS symptoms. Our study suggests that standard MD may not be suitable for all patients with IBS and likely needs to be personalized in those with increased symptoms.
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Dieta Mediterrânea , Gastroenteropatias , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Humanos , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/diagnóstico , Alimentos , DietaRESUMO
Nutrition and diet quality play key roles in preventing and slowing cognitive decline and have been linked to multiple brain disorders. This review compiles available evidence from preclinical studies and clinical trials on the impact of nutrition and interventions regarding major psychiatric conditions and some neurological disorders. We emphasize the potential role of diet-related microbiome alterations in these effects and highlight commonalities between various brain disorders related to the microbiome. Despite numerous studies shedding light on these findings, there are still gaps in our understanding due to the limited availability of definitive human trial data firmly establishing a causal link between a specific diet and microbially mediated brain functions and symptoms. The positive impact of certain diets on the microbiome and cognitive function is frequently ascribed with the anti-inflammatory effects of certain microbial metabolites or a reduction of proinflammatory microbial products. We also critically review recent research on pro- and prebiotics and nondietary interventions, particularly fecal microbiota transplantation. The recent focus on diet in relation to brain disorders could lead to improved treatment outcomes with combined dietary, pharmacological, and behavioral interventions.
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Encefalopatias , Microbioma Gastrointestinal , Transtornos Mentais , Humanos , Dieta , Encéfalo , Encefalopatias/metabolismoRESUMO
BACKGROUND: Patients with irritable bowel syndrome (IBS) show lower resilience than healthy controls (HCs), associated with greater symptom severity and worse quality of life. However, little is known about affected markers of resilience or the influence of sex. Furthermore, as resilience is complex, a comprehensive assessment, with multiple resilience measures, is needed. Therefore, we aimed to evaluate perceived and relative resilience and their neural correlates in men and women with IBS. METHODS: In 402 individuals (232 IBS [73.3% women] and 170 HCs [61.2% women]), perceived resilience was assessed by the Connor-Davidson Resilience Scale (CDRISC) and Brief Resilience Scale (BRS); relative resilience was assessed by the standardized residual of the Short Form-12 mental component summary score predicted by the Adverse Childhood Experiences score. Non-rotated partial least squares analysis of region-to-region resting-state connectivity data was used to define resilience-related signatures in HCs. Disease and sex-related differences within these signatures were investigated. KEY RESULTS: Scores on all resilience measures were lower in IBS than in HCs (p's < 0.05). In all three resilience-related signatures, patients with IBS showed reduced connectivity largely involving the central autonomic network (p's < 0.001). Men with IBS showed lower CDRISC scores than women with IBS, and greater reductions in CDRISC-related connectivity, associated with worse symptom severity (p < 0.05). CONCLUSIONS AND INFERENCES: Individuals with IBS show reduced perceived and relative resilience, with reduced connectivity suggesting impaired homeostasis maintenance. Men with IBS may show additional impairment in specific aspects of resilience. Treatments aimed at improving resilience may benefit patients with IBS, especially men with IBS.
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Síndrome do Intestino Irritável , Testes Psicológicos , Resiliência Psicológica , Humanos , Masculino , Feminino , Qualidade de Vida , Índice de Gravidade de DoençaRESUMO
Experiences of discrimination are associated with adverse health outcomes, including obesity. However, the mechanisms by which discrimination leads to obesity remain unclear. Utilizing multi-omics analyses of neuroimaging and fecal metabolites, we investigated the impact of discrimination exposure on brain reactivity to food images and associated dysregulations in the brain-gut-microbiome system. We show that discrimination is associated with increased food-cue reactivity in frontal-striatal regions involved in reward, motivation and executive control; altered glutamate-pathway metabolites involved in oxidative stress and inflammation as well as preference for unhealthy foods. Associations between discrimination-related brain and gut signatures were skewed towards unhealthy sweet foods after adjusting for age, diet, body mass index, race and socioeconomic status. Discrimination, as a stressor, may contribute to enhanced food-cue reactivity and brain-gut-microbiome disruptions that can promote unhealthy eating behaviors, leading to increased risk for obesity. Treatments that normalize these alterations may benefit individuals who experience discrimination-related stress.
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BACKGROUND: Living in a disadvantaged neighborhood is associated with worse health outcomes, including brain health, yet the underlying biological mechanisms are incompletely understood. We investigated the relationship between neighborhood disadvantage and cortical microstructure, assessed as the T1-weighted/T2-weighted ratio (T1w/T2w) on magnetic resonance imaging, and the potential mediating roles of body mass index (BMI) and stress, as well as the relationship between trans-fatty acid intake and cortical microstructure. METHODS: Participants comprised 92 adults (27 men; 65 women) who underwent neuroimaging and provided residential address information. Neighborhood disadvantage was assessed as the 2020 California State area deprivation index (ADI). The T1w/T2w ratio was calculated at four cortical ribbon levels (deep, lower-middle, upper-middle, and superficial). Perceived stress and BMI were assessed as potential mediating factors. Dietary data was collected in 81 participants. RESULTS: Here, we show that worse ADI is positively correlated with BMI (r = 0.27, p = .01) and perceived stress (r = 0.22, p = .04); decreased T1w/T2w ratio in middle/deep cortex in supramarginal, temporal, and primary motor regions (p < .001); and increased T1w/T2w ratio in superficial cortex in medial prefrontal and cingulate regions (p < .001). Increased BMI partially mediates the relationship between worse ADI and observed T1w/T2w ratio increases (p = .02). Further, trans-fatty acid intake (high in fried fast foods and obesogenic) is correlated with these T1w/T2w ratio increases (p = .03). CONCLUSIONS: Obesogenic aspects of neighborhood disadvantage, including poor dietary quality, may disrupt information processing flexibility in regions involved in reward, emotion regulation, and cognition. These data further suggest ramifications of living in a disadvantaged neighborhood on brain health.
Neighborhood disadvantage (a combination of low average income, more people leaving education earlier, crowding, lack of complete plumbing, etc.) is known to impact the health of people's brains. We evaluated whether neighborhood disadvantage was associated with differences in the structure of people's brains, and whether any differences were related to an unhealthily high weight and a high intake of trans-fatty acids, a component of fried fast food, on the structure of people's brains. Based on our results, regions of the brain that are involved in reward, emotion and gaining knowledge and understanding might be affected by aspects of neighborhood disadvantage that contribute to obesity, such as poor dietary quality. This suggests that it might be important to make healthier food more readily available in disadvantaged neighborhoods to improve the health of people's brains.
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The Specialized Center of Research Excellence (SCORE) on sex differences at University of California, Los Angeles (UCLA) has a long track record studying bidirectional interactions between different organs and the brain in health and disease with a strong focus on sex as a biological variable (SABV). While the initial focus was on brain-gut interactions in irritable bowel syndrome (IBS), one of the most common disorders of gut-brain interaction, the scope of our Center's research has expanded to a range of different diseases, including inflammatory bowel disease, alcohol use disorder, obesity, urological chronic pelvic pain syndrome, and vulvodynia. This expansion of research focused on the role of brain-body and brain-gut microbiome interactions in these various disorders, aligning well with the increasing importance of multidisciplinary and interdisciplinary team science. The SCORE's Career Enhancement Core (CEC) has modeled team science as applied to SABV research, with educational and training opportunities, a mentoring program, seed grant funding, and other career development experiences that enable mentees to work across the disciplines involved in brain body research. The CEC goals are: (1) To provide seed grant funds for innovative research relevant to the overall SCORE mission and research program; (2) to recruit and foster the career development of students, trainees, and junior investigators who conduct research focused on sex differences or women's health in IBS and chronic constipation and other brain-gut disorders; (3) to facilitate and promote collaboration between the UCLA SCORE and other academic programs involved in women's health education and research; and (4) to promote the importance of SABV through community outreach using collaborative and innovative approaches. These goals focus on establishing the leading research center in sex differences in basic, translational, and clinical aspects of brain-body interactions and on providing women and underrepresented individuals with research opportunities needed to become independent investigators.
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Síndrome do Intestino Irritável , Tutoria , Humanos , Feminino , Masculino , Mentores , Saúde da Mulher , EncéfaloRESUMO
Obesity contributes to physical comorbidities and mental health consequences. We explored whether physical activity could influence more than metabolic regulation and result in psychological benefits through the brain-gut microbiome (BGM) system in a population with high BMI. Fecal samples were obtained for 16 s rRNA profiling and fecal metabolomics, along with psychological and physical activity questionnaires. Whole brain resting-state functional MRI was acquired, and brain connectivity metrics were calculated. Higher physical activity was significantly associated with increased connectivity in inhibitory appetite control brain regions, while lower physical activity was associated with increased emotional regulation network connections. Higher physical activity was also associated with microbiome and metabolite signatures protective towards mental health and metabolic derangements. The greater resilience and coping, and lower levels of food addiction seen with higher physical activity, may be explained by BGM system differences. These novel findings provide an emphasis on the psychological and resilience benefits of physical activity, beyond metabolic regulation and these influences seem to be related to BGM interactions.
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Microbioma Gastrointestinal , Microbiota , Humanos , Microbioma Gastrointestinal/genética , Encéfalo/fisiologia , Obesidade , Exercício FísicoRESUMO
Neuroticism is one of the most robust risk factors for addictive behaviors including food addiction (a key contributor to obesity), although the associated mechanisms are not well understood. A transdiagnostic approach was used to identify the neuroticism-related neuropsychological and gut metabolomic patterns associated with food addiction. Predictive modeling of neuroticism was implemented using multimodal features (23 clinical, 13,531 resting-state functional connectivity (rsFC), 336 gut metabolites) in 114 high body mass index (BMI ≥25 kg/m2) (cross-sectional) participants. Gradient boosting machine and logistic regression models were used to evaluate classification performance for food addiction. Neuroticism was significantly associated with food addiction (P < 0.001). Neuroticism-related features predicted food addiction with high performance (89% accuracy). Multimodal models performed better than single-modal models in predicting food addiction. Transdiagnostic alterations corresponded to rsFC involved in the emotion regulation, reward, and cognitive control and self-monitoring networks, and the metabolite 3-(4-hydroxyphenyl) propionate, as well as anxiety symptoms. Neuroticism moderated the relationship between BMI and food addiction. Neuroticism drives neuropsychological and gut microbial signatures implicated in dopamine synthesis and inflammation, anxiety, and food addiction. Such transdiagnostic models are essential in identifying mechanisms underlying food addiction in obesity, as it can help develop multiprong interventions to improve symptoms.
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Comportamento Aditivo , Dependência de Alimentos , Microbioma Gastrointestinal , Humanos , Neuroticismo , Estudos Transversais , Encéfalo/diagnóstico por imagem , Obesidade , Comportamento Aditivo/psicologiaRESUMO
Investigating sex as a biological variable is key to determine obesity manifestation and treatment response. Individual neuroimaging modalities have uncovered mechanisms related to obesity and altered ingestive behaviours. However, few, if any, studies have integrated data from multi-modal brain imaging to predict sex-specific brain signatures related to obesity. We used a data-driven approach to investigate how multi-modal MRI and clinical features predict a sex-specific signature of participants with high body mass index (overweight/obese) compared to non-obese body mass index in a sex-specific manner. A total of 78 high body mass index (55 female) and 105 non-obese body mass index (63 female) participants were enrolled in a cross-sectional study. All participants classified as high body mass index had a body mass index greater than 25â kg/m2 and non-obese body mass index had a body mass index between 19 and 20â kg/m2. Multi-modal neuroimaging (morphometry, functional resting-state MRI and diffusion-weighted scan), along with a battery of behavioural and clinical questionnaires were acquired, including measures of mood, early life adversity and altered ingestive behaviours. A Data Integration Analysis for Biomarker discovery using Latent Components was conducted to determine whether clinical features, brain morphometry, functional connectivity and anatomical connectivity could accurately differentiate participants stratified by obesity and sex. The derived models differentiated high body mass index against non-obese body mass index participants, and males with high body mass index against females with high body mass index obtaining balanced accuracies of 77 and 75%, respectively. Sex-specific differences within the cortico-basal-ganglia-thalamic-cortico loop, the choroid plexus-CSF system, salience, sensorimotor and default-mode networks were identified, and were associated with early life adversity, mental health quality and greater somatosensation. Results showed multi-modal brain signatures suggesting sex-specific cortical mechanisms underlying obesity, which fosters clinical implications for tailored obesity interventions based on sex.
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A growing body of preclinical and clinical literature suggests that brain-gut-microbiota interactions may contribute to obesity pathogenesis. In this study, we use a machine learning approach to leverage the enormous amount of microstructural neuroimaging and fecal metabolomic data to better understand key drivers of the obese compared to overweight phenotype. Our findings reveal that although gut-derived factors play a role in this distinction, it is primarily brain-directed changes that differentiate obese from overweight individuals. Of the key gut metabolites that emerged from our model, many are likely at least in part derived or influenced by the gut-microbiota, including some amino-acid derivatives. Remarkably, key regions outside of the central nervous system extended reward network emerged as important differentiators, suggesting a role for previously unexplored neural pathways in the pathogenesis of obesity.
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Microbioma Gastrointestinal , Sobrepeso , Humanos , Sobrepeso/metabolismo , Obesidade/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Microbioma Gastrointestinal/genética , Metabolômica , Fezes/químicaRESUMO
We investigated the relationship between neighborhood disadvantage (area deprivation index [ADI]) and intracortical myelination (T1-weighted/T2-weighted ratio at deep to superficial cortical levels), and the potential mediating role of the body mass index (BMI) and perceived stress in 92 adults. Worse ADI was correlated with increased BMI and perceived stress (p's<.05). Non-rotated partial least squares analysis revealed associations between worse ADI and decreased myelination in middle/deep cortex in supramarginal, temporal, and primary motor regions and increased myelination in superficial cortex in medial prefrontal and cingulate regions (p<.001); thus, neighborhood disadvantage may influence the flexibility of information processing involved in reward, emotion regulation, and cognition. Structural equation modelling revealed increased BMI as partially mediating the relationship between worse ADI and observed myelination increases (p=.02). Further, trans-fatty acid intake was correlated with observed myelination increases (p=.03), suggesting the importance of dietary quality. These data further suggest ramifications of neighborhood disadvantage on brain health.