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1.
Vaccines (Basel) ; 12(6)2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38932366

RESUMEN

Although vaccines address critical public health needs, inter-individual differences in responses are not always considered in their development. Understanding the underlying basis for these differences is needed to optimize vaccine effectiveness and ultimately improve disease control. In this pilot study, pre- and post-antiviral immunological and gut microbiota features were characterized to examine inter-individual differences in SARS-CoV-2 mRNA vaccine response. Blood and stool samples were collected before administration of the vaccine and at 2-to-4-week intervals after the first dose. A cohort of 14 adults was separated post hoc into two groups based on neutralizing antibody levels (high [HN] or low [LN]) at 10 weeks following vaccination. Bivariate correlation analysis was performed to examine associations between gut microbiota, inflammation, and neutralization capacity at that timepoint. These analyses revealed significant differences in gut microbiome composition and inflammation states pre-vaccination, which predicted later viral neutralization capacity, with certain bacterial taxa, such as those in the genus Prevotella, found at higher abundance in the LN vs HN group that were also negatively correlated with a panel of inflammatory factors such as IL-17, yet positively correlated with plasma levels of the high mobility group box 1 (HMGB-1) protein at pre-vaccination. In particular, we observed a significant inverse relationship (Pearson = -0.54, p = 0.03) between HMGB-1 pre-vaccination and neutralization capacity at 10 weeks post-vaccination. Consistent with known roles as mediators of inflammation, our results altogether implicate HMGB-1 and related gut microbial signatures as potential biomarkers in predicting SARS-CoV-2 mRNA vaccine effectiveness measured by the production of viral neutralization antibodies.

2.
Nutrients ; 16(10)2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38794639

RESUMEN

In this interventional pilot study, we investigated the effects of a modified ketogenic diet (KD) on children with autism spectrum disorder (ASD). We previously observed improved behavioral symptoms in this cohort following the KD; this trial was registered with Clinicaltrials.gov (NCT02477904). This report details the alterations observed in the microbiota, inflammation markers, and microRNAs of seven children following a KD for a duration of 4 months. Our analysis included blood and stool samples, collected before and after the KD. After 4 months follow up, we found that the KD led to decreased plasma levels of proinflammatory cytokines (IL-12p70 and IL-1b) and brain-derived neurotrophic factor (BDNF). Additionally, we observed changes in the gut microbiome, increased expression of butyrate kinase in the gut, and altered levels of BDNF-associated miRNAs in the plasma. These cohort findings suggest that the KD may positively influence ASD sociability, as previously observed, by reducing inflammation, reversing gut microbial dysbiosis, and impacting the BDNF pathway related to brain activity.


Asunto(s)
Trastorno del Espectro Autista , Factor Neurotrófico Derivado del Encéfalo , Citocinas , Dieta Cetogénica , Microbioma Gastrointestinal , MicroARNs , Niño , Preescolar , Femenino , Humanos , Masculino , Trastorno del Espectro Autista/microbiología , Trastorno del Espectro Autista/dietoterapia , Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/sangre , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Citocinas/sangre , Disbiosis , Inflamación , MicroARNs/sangre , MicroARNs/metabolismo , Proyectos Piloto
4.
Am J Hum Genet ; 111(3): 456-472, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38367619

RESUMEN

The impact of tobacco exposure on health varies by race and ethnicity and is closely tied to internal nicotine dose, a marker of carcinogen uptake. DNA methylation is strongly responsive to smoking status and may mediate health effects, but study of associations with internal dose is limited. We performed a blood leukocyte epigenome-wide association study (EWAS) of urinary total nicotine equivalents (TNEs; a measure of nicotine uptake) and DNA methylation measured using the MethylationEPIC v1.0 BeadChip (EPIC) in six racial and ethnic groups across three cohort studies. In the Multiethnic Cohort Study (discovery, n = 1994), TNEs were associated with differential methylation at 408 CpG sites across >250 genomic regions (p < 9 × 10-8). The top significant sites were annotated to AHRR, F2RL3, RARA, GPR15, PRSS23, and 2q37.1, all of which had decreasing methylation with increasing TNEs. We identified 45 novel CpG sites, of which 42 were unique to the EPIC array and eight annotated to genes not previously linked with smoking-related DNA methylation. The most significant signal in a novel gene was cg03748458 in MIR383;SGCZ. Fifty-one of the 408 discovery sites were validated in the Singapore Chinese Health Study (n = 340) and the Southern Community Cohort Study (n = 394) (Bonferroni corrected p < 1.23 × 10-4). Significant heterogeneity by race and ethnicity was detected for CpG sites in MYO1G and CYTH1. Furthermore, TNEs significantly mediated the association between cigarettes per day and DNA methylation at 15 sites (average 22.5%-44.3% proportion mediated). Our multiethnic study highlights the transethnic and ethnic-specific methylation associations with internal nicotine dose, a strong predictor of smoking-related morbidities.


Asunto(s)
MicroARNs , Fumadores , Humanos , Nicotina , Epigénesis Genética/genética , Epigenoma , Estudios de Cohortes , Estudios Prospectivos , Estudio de Asociación del Genoma Completo , Metilación de ADN/genética , Islas de CpG/genética , Receptores de Péptidos/genética , Receptores Acoplados a Proteínas G/genética
5.
Sci Rep ; 14(1): 355, 2024 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-38172612

RESUMEN

While obesity is a risk factor for post-acute sequelae of SARS-CoV-2 infection (PASC, "long-COVID"), the mechanism(s) underlying this phenomenon remains poorly understood. To address this gap in knowledge, we performed a 6-week longitudinal study to examine immune activity and gut microbiome dysbiosis in post-acute stage patients recovering from SARS-CoV-2 infection. Self-reported symptom frequencies and blood samples were collected weekly, with plasma assessed by ELISA and Luminex for multiple biomarkers and immune cell profiling. DNA from stool samples were collected at the early stage of recovery for baseline assessments of gut microbial composition and diversity using 16S-based metagenomic sequencing. Multiple regression analyses revealed obesity-related PASC linked to a sustained proinflammatory immune profile and reduced adaptive immunity, corresponding with reduced gut microbial diversity. In particular, enhanced signaling of the high mobility group box 1 (HMGB1) protein was found to associate with this dysregulation, with its upregulated levels in plasma associated with significantly impaired viral neutralization that was exacerbated with obesity. These findings implicate HMGB1 as a candidate biomarker of PASC, with potential applications for risk assessment and targeted therapies.


Asunto(s)
COVID-19 , Proteína HMGB1 , Microbiota , Humanos , COVID-19/complicaciones , Progresión de la Enfermedad , Proteína HMGB1/genética , Estudios Longitudinales , Obesidad/complicaciones , Síndrome Post Agudo de COVID-19 , SARS-CoV-2
6.
Health Promot Pract ; 24(6): 1087-1090, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37877635

RESUMEN

Indigenous peoples, including Native Hawaiians and Pacific Islanders (NHPIs), experience significant cardiometabolic health disparities arising in large part from rapid changes to their diets and food systems. Innovative food sovereignty initiatives led by NHPIs are needed to address these disparities. This article describes a community-based participatory research study that incorporates social and biological measures to examine the impact of an Indigenous-led land-based food sovereignty youth leadership program on health disparities among NHPI youth in Hawai'i. Grounded in the Indigenous knowledge that holistic health and wellbeing of people is inseparable from that of the environment and to counter rampant food insecurity in their community of Wai'anae, O'ahu, MA'O Organic Farms developed a Youth Leadership Training (YLT) program that offers education, nutrition, physical activity, and access to health care. The program also engages YLT interns and their social networks in health education and research in the ongoing Mauli Ola study. Preliminary data from this study affirm the need to address the disproportionately high rates of obesity, type 2 diabetes mellitus (T2D), and poor mental health conditions among young NHPIs in the Wai'anae community, and how the YLT program may provide an effective approach to address this need. Our unique academic-community partnership underscores the importance of social and biomedical research to understand health disparities in the NHPI population, which present novel avenues to enable disease prevention. The outcomes of the Mauli Ola study may serve as a valuable model for health disparities research while leveraging ongoing social programs that support Indigenous food sovereignty.


Asunto(s)
Diabetes Mellitus Tipo 2 , Inequidades en Salud , Nativos de Hawái y Otras Islas del Pacífico , Adolescente , Humanos , Hawaii/epidemiología , Agricultura Orgánica , Pueblos Isleños del Pacífico
8.
Eur J Biomed Res ; 2(3): 17-23, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37525697

RESUMEN

Whole-genome SARS-CoV-2 sequencing tools are crucial for tracking the COVID-19 pandemic. However, current techniques require sampling of actively infectious patients following COVID-19 testing to recover enough SARS-CoV-2 RNA from the nasopharyngeal passage, which rapidly clears during the first few weeks of infection. A prospective assessment of the viral genome sourced from recovered non-infectious patients would greatly facilitate epidemiological tracking. Thus, we developed a protocol to isolate and sequence the genome of SARS-CoV-2 from stool samples of post-acute SARS-CoV-2 patients, at timepoints ranging from 10-120 days after onset of symptoms. Stool samples were collected from patients at varying timepoints post-convalescence, and viral DNA was isolated and sequenced using the QIAamp Viral RNA Mini Kit (Qiagen Inc.) and Ion Ampliseq™ Library Kit Plus (Life Technologies Corporation). Capacity of neutralizing antibodies in patient plasma was tested using a Luminex panel (Coronavirus Ig Total Human 11-Plex ProcartaPlex™ Panel, ThermoFisher). Of 64 samples obtained from post-acute patients, 21 (32.8%) yielded sufficient material for whole-genome sequencing. This allowed us to identify widely divergent phylogenetic relativity of the SARS-CoV-2 genome from post-acute patients living in the same households and infected around the same time. Additionally, we observed that individuals who recovered from infection expressed varying degrees of antibodies against SARS-CoV-2 structural proteins that corresponded to distinct variants. Interestingly, we identified a novel point mutation in the viral genome where infected patients expressed antibodies with a significantly reduced capacity to neutralize the virus in vitro relative to that of those infected with the wild-type strain. Altogether, we demonstrate a protocol to successfully sequence the SARS-CoV-2 genome from stool samples from patients up to 4 months post-infection, which can be applied to studies that assess the relationship between variants and immune response post-hoc and safe monitoring of the SARS-CoV-2 genome during the pandemic.

9.
Front Genet ; 14: 1125217, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37152987

RESUMEN

Introduction: Native Hawaiian and other Pacific Islander (NHPI) populations experience higher rates of immunometabolic diseases compared to other racial-ethnic groups in Hawaii. As annual NHPI mortality rates for suicide and type 2 diabetes mellitus (T2DM) exceed those of the state as a whole, understanding the social and biological mechanisms underlying these disparities are urgently needed to enable preventive strategies. Methods: A community-based approach was used to investigate the immunoepigenetic-gut microbiome axis in an NHPI-enriched cohort of Oahu residents (N = 68). Self-esteem (SE) data was collected using a modified Rosenberg self-esteem (SE) assessment as a proxy measure for mental wellbeing in consideration for cultural competency. T2DM status was evaluated using point-of-care A1c (%) tests. Stool samples were collected for 16s-based metagenomic sequencing analyses. Plasma from blood samples were isolated by density-gradient centrifugation. Peripheral blood mononuclear cells (PBMCs) were collected from the same samples and enriched for monocytes using negative selection techniques. Flow-cytometry was used for immunoprofiling assays. Monocyte DNA was extracted for Illumina EPIC array-based methylation analysis. Results: Compared to individuals with normal SE (NSE), those with low SE (LSE) exhibited significantly higher plasma concentrations (pg/ml) of proinflammatory cytokines IL-8 (p = 0.051) and TNF-α (p = 0.011). Metagenomic analysis revealed that the relative abundance (%) of specific gut bacteria significantly differed between SE groups - some of which directly correlated with SE scores. Gene ontology analysis revealed that 104 significantly differentially methylated loci (DML) between SE groups were preferentially located at genes involved in immunometabolic processes. Horvath clock analyses indicated epigenetic age (Epi-Age) deceleration in individuals with LSE and acceleration in individuals with NSE (p = 0.042), yet was not reproduced by other clocks. Discussion: These data reveal novel differences in the immunoepigenetic-gut microbiome axis with respect to SE, warranting further investigation into its relationship to brain activity and mental health in NHPI. Unexpected results from Epi-Age analyses warrant further investigation into the relationship between biological age and disparate health outcomes among the NHPI population. The modifiable component of epigenetic processes and the gut microbiome makes this axis an attractive target for potential therapeutics, biomarker discovery, and novel prevention strategies.

11.
Am J Public Health ; 112(S9): S896-S899, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36108254

RESUMEN

Native Hawaiians and other Pacific Islanders (NHPIs) across the country have experienced significant disparities because of the COVID-19 pandemic. The Pacific Alliance Against COVID-19 used a community-based participatory approach involving academic and community partners to expand sustainable COVID-19 testing capacity and mitigate the severe consequences among NHPI communities in Hawaii. We describe the approach of this one-year study, some of the results, and how the data are being used to inform next steps for the communities. Clinical Trials.gov identifier: NCT04766333. (Am J Public Health. 2022;112(S9):S896-S899. https://doi.org/10.2105/AJPH.2022.306973).


Asunto(s)
COVID-19 , Vacunas , Humanos , Hawaii/epidemiología , Nativos de Hawái y Otras Islas del Pacífico , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Prueba de COVID-19 , Pandemias
12.
Vaccines (Basel) ; 10(9)2022 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-36146513

RESUMEN

Vaccine hesitancy remains a significant barrier to achieving herd immunity and preventing the further spread of COVID-19. Understanding contributors to vaccine hesitancy and how they change over time may improve COVID-19 mitigation strategies and public health policies. To date, no mechanism explains how trust in and consumption of different sources of information affect vaccine uptake. A total of 1594 adults enrolled in our COVID-19 testing program completed standardized surveys on demographics, vaccination status, use, reliance, and trust in sources of COVID-19 information, from September to October 2021, during the COVID-19 Delta wave. Of those, 802 individuals (50.3%) completed a follow-up survey, from January to February 2022, during the Omicron-wave. Regression analyses were performed to understand contributors to vaccine and booster uptake over time. Individuals vaccinated within two months of eligibility (early vaccinees) tended to have more years of schooling, with greater trust in and consumption of official sources of COVID-19 information, compared to those who waited 3-6 months (late vaccinees), or those who remained unvaccinated at 6 months post-eligibility (non-vaccinees). Most (70.1%) early vaccinees took the booster shot, compared to only 30.5% of late vaccinees, with the latter group gaining trust and consumption of official information after four months. These data provide the foundation for a mechanism based on the level of trust in and consumption of official information sources, where those who increased their level of trust in and consumption of official information sources were more likely to receive a booster. This study shows that social factors, including education and individual-level degree of trust in (and consumption of) sources of COVID-19 information, interact and change over time to be associated with vaccine and booster uptakes. These results are critical for the development of effective public health policies and offer insights into hesitancy over the course of the COVID-19 vaccine and booster rollout.

13.
Clin Epigenetics ; 14(1): 91, 2022 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-35851422

RESUMEN

BACKGROUND: Native Hawaiians are disproportionately affected by type 2 diabetes mellitus (DM), a chronic metabolic, non-communicable disease characterized by hyperglycemia and systemic inflammation. Unrelenting systemic inflammation  frequently leads to a cascade of multiple comorbidities associated with DM, including cardiovascular disease, microvascular complications, and renal dysfunction. Yet few studies have examined the link between chronic inflammation at a cellular level and its relationship to standard DM therapies such as diabetes-specific lifestyle and social support education, well recognized as the cornerstone of clinical standards of diabetes care. This pilot study was initiated to explore the association of monocyte inflammation using epigenetic, immunologic, and clinical measures following a 3-month diabetes-specific social support program among high-risk Native Hawaiian adults with DM. RESULTS: From a sample of 16 Native Hawaiian adults with DM, monocytes enriched from peripheral blood mononuclear cells (PBMCs) of 8 individuals were randomly selected for epigenomic analysis. Using the Illumina HumanMethylation450 BeadChip microarray, 1,061 differentially methylated loci (DML) were identified in monocytes of participants at baseline and 3 months following a DM-specific social support program (DM-SSP). Gene ontology analysis showed that these DML were enriched within genes involved in immune, metabolic, and cardiometabolic pathways, a subset of which were also significantly differentially expressed. Ex vivo analysis of immune function showed improvement post-DM-SSP compared with baseline, characterized by attenuated interleukin 1ß and IL-6 secretion from monocytes. Altered cytokine secretion in response to the DM-SSP was significantly associated with changes in the methylation and gene expression states of immune-related genes in monocytes between intervention time points. CONCLUSIONS: Our pilot study provides preliminary evidence of changes to inflammatory monocyte activity, potentially driven by epigenetic modifications, 3 months following a DM-specific SSP intervention. These novel alterations in the trajectory of monocyte inflammatory states were identified at loci that regulate transcription of immune and metabolic genes in high-risk Native Hawaiians with DM, suggesting a relationship between improvements in psychosocial behaviors and shifts in the immunoepigenetic patterns following a diabetes-specific SSP. Further research is warranted to investigate how social support influences systemic inflammation via immunoepigenetic modifications in chronic inflammatory diseases such as DM.


Asunto(s)
Diabetes Mellitus Tipo 2 , Monocitos , Adulto , Metilación de ADN , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Inflamación/genética , Inflamación/metabolismo , Leucocitos Mononucleares/metabolismo , Nativos de Hawái y Otras Islas del Pacífico/genética , Proyectos Piloto , Apoyo Social
14.
Vaccines (Basel) ; 10(6)2022 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-35746577

RESUMEN

Native Hawaiians and other Pacific Islanders (NHPIs) were disproportionately impacted by COVID-19 and remain significantly under-vaccinated against SARS-CoV-2. To understand vaccine hesitancy, we surveyed 1124 adults residing in a region with one of the lowest vaccination rates in Hawaii during our COVID-19 testing program. Probit regression analysis revealed that race/ethnicity was not directly associated with the probability of vaccine uptake. Instead, a higher degree of trust in official sources of COVID-19 information increased the probability of vaccination by 20.68%, whereas a higher trust in unofficial sources decreased the probability of vaccination by 12.49% per unit of trust. These results revealed a dual and opposing role of trust on vaccine uptake. Interestingly, NHPIs were the only racial/ethnic group to exhibit a significant positive association between trust in and consumption of unofficial sources of COVID-19 information, which explained the vaccine hesitancy observed in this indigenous population. These results offer novel insight relevant to COVID-19 mitigation efforts in minority populations.

15.
Infect Dis Clin North Am ; 36(2): 295-308, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35636901

RESUMEN

The violence and victimization brought by colonization and slavery and justified for over a century by race-based science have resulted in enduring inequities for black, Indigenous and people of color (BIPOC) across the United States. This is particularly true if BIPOC individuals have other intersecting devalued identities. We highlight how such longstanding inequities paved the way for the disproportionate burdens of coronavirus disease 2019 (COVID-19) among the BIPOC populations across the country and provide recommendations on how to improve COVID-19 mitigation strategies with the goal of eliminating disparities.


Asunto(s)
COVID-19 , Pandemias , COVID-19/epidemiología , Humanos , Pandemias/prevención & control , Estados Unidos/epidemiología
16.
Vaccines (Basel) ; 10(5)2022 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-35632529

RESUMEN

Having been affected by the highest increase in COVID-19 cases since the start of the pandemic, Honolulu and Maui counties in Hawaii implemented vaccine passport mandates for select industries in September 2021. However, the degree to which such mandates impacted COVID-19 mitigation efforts and economics remains poorly understood. Herein, we describe the effects of these mandates on changes in three areas using difference-in-difference regression models: (1) business foot traffic; (2) number of COVID-19 cases per 100,000 individuals, and (3) COVID-19 vaccination rates across counties affected or unaffected by the mandates. We observed that although businesses affected by mandates experienced a 6.7% decrease in foot traffic over the 14 weeks after the mandates were implemented, the number of COVID-19 cases decreased by 19.0%. Notably, the vaccination rate increased by 1.41% in counties that implemented mandates. In addition, towards the end of the studied period, the level of foot traffic at impacted businesses converged towards the level of that of non-impacted businesses. As such, the trade-off in temporary losses at businesses was met with significant gains in public health and safety.

17.
Front Cell Infect Microbiol ; 12: 1035641, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36619744

RESUMEN

Native Hawaiians and Pacific Islanders (NHPIs) suffer from higher prevalence of and mortality to type 2 diabetes mellitus (T2DM) than any other major race/ethnic group in Hawaii. Health inequities in this indigenous population was further exacerbated by the SARS-CoV-2 pandemic. T2DM progression and medical complications exacerbated by COVID-19 are partially regulated by the gut microbiome. However, there is limited understanding of the role of gut bacteria in the context of inflammation-related diseases of health disparities including T2DM and obesity. To address these gaps, we used a community-based research approach from a cohort enriched with NHPI residents on the island of Oahu, Hawaii (N=138). Gut microbiome profiling was achieved via 16s rDNA metagenomic sequencing analysis from stool DNA. Gut bacterial capacity for butyrate-kinase (BUK)-mediated fiber metabolism was assessed using quantitative PCR to measure the abundance of BUK DNA and RNA relative to total bacterial load per stool sample. In our cohort, age positively correlated with hemoglobin A1c (%; R=0.39; P<0.001) and body mass index (BMI; R=0.28; P<0.001). The relative abundance of major gut bacterial phyla significantly varied across age groups, including Bacteroidetes (P<0.001), Actinobacteria (P=0.007), and Proteobacteria (P=0.008). A1c was negatively correlated with the relative levels of BUK DNA copy number (R=-0.17; P=0.071) and gene expression (R=-0.33; P=0.003). Interestingly, we identified specific genera of gut bacteria potentially mediating the effects of diet on metabolic health in this cohort. Additionally, α-diversity among gut bacterial genera significantly varied across T2DM and BMI categories. Together, these results provide insight into age-related differences in gut bacteria that may influence T2DM and obesity in NHPIs. Furthermore, we observed overlapping patterns between gut bacteria and T2DM risk factors, indicating more nuanced, interdependent interactions among these factors as partial determinants of health outcomes. This study adds to the paucity of NHPI-specific data to further elucidate the biological characteristics associated with pre-existing health inequities in this racial/ethnic group that is significantly underrepresented in biomedical research.


Asunto(s)
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Obesidad , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/microbiología , Hemoglobina Glucada , Hawaii/epidemiología , Nativos de Hawái y Otras Islas del Pacífico , Obesidad/epidemiología , Obesidad/microbiología
18.
Front Neurosci ; 16: 1023665, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36817099

RESUMEN

Introduction: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction, communication and repetitive, restrictive behaviors, features supported by cortical activity. Given the importance of the subventricular zone (SVZ) of the lateral ventrical to cortical development, we compared molecular, cellular, and structural differences in the SVZ and linked cortical regions in specimens of ASD cases and sex and age-matched unaffected brain. Methods: We used magnetic resonance imaging (MRI) and diffusion tractography on ex vivo postmortem brain samples, which we further analyzed by Whole Genome Bisulfite Sequencing (WGBS), Flow Cytometry, and RT qPCR. Results: Through MRI, we observed decreased tractography pathways from the dorsal SVZ, increased pathways from the posterior ventral SVZ to the insular cortex, and variable cortical thickness within the insular cortex in ASD diagnosed case relative to unaffected controls. Long-range tractography pathways from and to the insula were also reduced in the ASD case. FACS-based cell sorting revealed an increased population of proliferating cells in the SVZ of ASD case relative to the unaffected control. Targeted qPCR assays of SVZ tissue demonstrated significantly reduced expression levels of genes involved in differentiation and migration of neurons in ASD relative to the control counterpart. Finally, using genome-wide DNA methylation analyses, we identified 19 genes relevant to neurological development, function, and disease, 7 of which have not previously been described in ASD, that were significantly differentially methylated in autistic SVZ and insula specimens. Conclusion: These findings suggest a hypothesis that epigenetic changes during neurodevelopment alter the trajectory of proliferation, migration, and differentiation in the SVZ, impacting cortical structure and function and resulting in ASD phenotypes.

19.
Cereb Cortex ; 32(6): 1200-1211, 2022 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-34455432

RESUMEN

Early interventions for autism spectrum disorder (ASD) are increasingly available, while only 42-50% of ASD children are diagnosed before 3 years old (YO). To identify neuroimaging biomarkers for early ASD diagnosis, we evaluated surface- and voxel-based brain morphometry in participants under 3YO who were later diagnosed with ASD. Magnetic resonance imaging data were retrospectively obtained from patients later diagnosed with ASD at Boston Children's Hospital. The ASD participants with comorbidities such as congenital disorder, epilepsy, and global developmental delay/intellectual disability were excluded from statistical analyses. Eighty-five structural brain magnetic resonance imaging images were collected from 81 participants under 3YO and compared with 45 images from 45 gender- and age-matched nonautistic controls (non-ASD). Using an Infant FreeSurfer pipeline, 236 regionally distributed measurements were extracted from each scan. By t-tests and linear mixed models, the smaller nucleus accumbens and larger bilateral lateral, third, and fourth ventricles were identified in the ASD group. Vertex-wise t-statistical maps showed decreased thickness in the caudal anterior cingulate cortex and increased thickness in the right medial orbitofrontal cortex in ASD. The smaller bilateral accumbens nuclei and larger cerebral ventricles were independent of age, gender, or gestational age at birth, suggesting that there are MRI-based biomarkers in prospective ASD patients before they receive the diagnosis and that the volume of the nucleus accumbens and cerebral ventricles can be key MRI-based early biomarkers to predict the emergence of ASD.


Asunto(s)
Trastorno del Espectro Autista , Trastorno del Espectro Autista/diagnóstico por imagen , Trastorno del Espectro Autista/patología , Biomarcadores , Ventrículos Cerebrales/patología , Preescolar , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Núcleo Accumbens/diagnóstico por imagen , Estudios Prospectivos , Estudios Retrospectivos
20.
BMC Pregnancy Childbirth ; 21(1): 558, 2021 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-34399704

RESUMEN

BACKGROUND: Consumption of a diet with high adherence to a Mediterranean diet pattern (MDP) has been associated with a favorable gastrointestinal tract (GIT) microbiome. A healthy GIT microbiome in pregnancy, as defined by increased alpha diversity, is associated with lower chance of adverse perinatal outcomes. This study aimed to evaluate the impact of adherence to an MDP on GIT microbial diversity longitudinally throughout pregnancy. METHODS: Adherence to MDP was scored by the Alternate Mediterranean (aMED) Diet Quality Score, after being applied to a validated Food Frequency Questionnaire. Association of aMED Scores with GIT alpha diversity profiles were compared linearly and across time using a linear mixed model, including covariates of age, body mass index (BMI), ethnicity, and parity. RESULTS: Forty-one participants of Filipino, Japanese, Native Hawaiian, and Non-Hispanic White descent provided dietary information and microbiome samples during each trimester of pregnancy. Alpha diversity profiles changed over gestation, with decreased microbial diversity in the third trimester. aMED scores positively correlated with Chao1 Index and Observed Species Number (r = 0.244, p = 0.017, and r = 0.233, p = 0.023, respectively). The strongest association was detected in the third trimester (Chao 1: r = 0.43, p = 0.020, Observed Species Number: r = 0.41, p = 0.026). Participants with higher aMED scores had higher relative abundance of Acidaminoacaeae at the family level (p = 0.0169), as well as higher abundance of several species known to increase production of short chain fatty acids within the GIT. CONCLUSIONS: Adherence to MDP pattern is associated with increased maternal GIT microbial diversity, and promotes the abundance of bacteria that produce short chain fatty acids. Increased consumption of fruits, vegetables and legumes with low red meat consumption were key components driving this association. The effect of nutrition however, was less of an effect than pregnancy itself. Further studies are needed to determine if adherence to a Mediterranean diet translates not only into microbial health, but also into reduced risk of adverse pregnancy outcomes.


Asunto(s)
Dieta Mediterránea , Microbioma Gastrointestinal/fisiología , Adolescente , Adulto , Asiático , Femenino , Hawaii/epidemiología , Humanos , Japón/etnología , Persona de Mediana Edad , Filipinas/etnología , Embarazo , Complicaciones del Embarazo/epidemiología , Trimestres del Embarazo , Población Blanca , Adulto Joven
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