Examining the immunoepigenetic-gut microbiome axis in the context of self-esteem among Native Hawaiians and other Pacific Islanders.

Examining the immunoepigenetic-gut microbiome axis in the context of self-esteem among Native Hawaiians and other Pacific Islanders.
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DOI:
10.3389/fgene.2023.1125217
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发表时间:
2023
影响因子:
3.7
通讯作者:
Maunakea, Alika K. K.
Maunakea, Alika K. K.
中科院分区:
生物学3区
文献类型:
--
作者:
Becerra, Celyna Y. Y.;Wells, Riley K. K.;Kunihiro, Braden P. P.;Lee, Rosa H. H.;Umeda, Lesley;Allan, Nina P. P.;Rubas, Noelle C. C.;McCracken, Trevor A. A.;Nunokawa, Chandler K. L.;Lee, Ming-Hao;Pidlaoan, Felix Gerard S.;Phankitnirondorn, Krit;Dye, Christian K. K.;Yamamoto, Brennan Y.;Peres, Rafael;Juarez, Ruben;Maunakea, Alika K. K.

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简介:与夏威夷的其他种族相比,夏威夷土著和其他太平洋岛民(NHPI)人群的免疫代谢疾病发病率更高。由于自杀和2型糖尿病(T2 DM)的年度NHPI死亡率超过了整个国家,因此迫切需要了解这些差异背后的社会和生物学机制,以制定预防策略。 研究方法:使用基于社区的方法来研究Oakland居民(N = 68)的NHPI富集队列中的免疫表观遗传肠道微生物组轴。自尊(SE)的数据收集使用修改后的Rosenberg自尊(SE)评估作为一个代理措施,考虑到文化能力的心理健康。使用床旁A1 c(%)检测评价T2 DM状态。收集粪便样品用于基于16 s的宏基因组测序分析。通过密度梯度离心分离来自血液样品的血浆。从相同样品收集外周血单核细胞(PBMC),并使用阴性选择技术富集单核细胞。流式细胞术用于免疫分析测定。提取单核细胞DNA用于基于Illumina EPIC阵列的甲基化分析。 结果如下:与正常SE(NSE)个体相比,低SE(LSE)个体的促炎细胞因子IL-8(p = 0.051)和TNF-α(p = 0.011)血浆浓度(pg/ml)显著升高。宏基因组分析显示,特定肠道细菌的相对丰度(%)在SE组之间存在显著差异-其中一些与SE评分直接相关。基因本体分析显示,104个显着差异甲基化位点(DML)之间的SE组优先位于参与免疫代谢过程的基因。生物钟分析表明LSE个体的表观遗传年龄(Epi-Age)减速,NSE个体的表观遗传年龄(Epi-Age)加速(p = 0.042),但其他生物钟未再现。 讨论内容:这些数据揭示了免疫表观遗传肠道微生物组轴与SE的新差异,从而进一步研究了其与NHPI中大脑活动和心理健康的关系。意想不到的结果Epi-Age分析值得进一步调查NHPI人群的生物学年龄和不同的健康结果之间的关系。表观遗传过程和肠道微生物组的可修饰成分使该轴成为潜在治疗,生物标志物发现和新型预防策略的有吸引力的目标。
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.
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影响因子: 5.8
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