Integrative analysis of the oral microbiome of American Indian Infants and the impact of a childhood obesity-prevention home visiting program on early childhood caries

项目摘要/摘要 儿童早期龋病(ECC)具有破坏性和长期的健康后果。这些措施包括 更高的医疗费用、疼痛、感染、自尊降低、语言发育延迟、表现不佳 学校，以及随后不良的口腔和成年后的整体健康状况。儿童中ECC的患病率 与美国所有种族相比，美国印第安人(AI)家庭的比例要高得多，ECC 早在一岁时就会发生。儿童早期肥胖与健康差距密切相关 (ECO)，对于年幼的人工智能儿童来说至关重要，特别是在纳瓦霍社区，因为他们获得的机会有限 有营养的食物和干净安全的饮用水。饮食是ECC和ECO的关键贡献因素，其中高 含糖饮料(SSB)在六个月前的饮食糖摄入量和早期启动 这对纳瓦霍婴儿的这两种情况都有很大影响。频繁的糖类消费驱使人们选择 口腔微生物区系中最终导致龋病的致龋菌和相关代谢活动 发展。在两岁之前获得和增殖致龋菌与 会增加患龋齿的风险。然而，口腔微生物群的发展和糖的影响 纳瓦霍高危婴儿微生物区系模式的摄入量减少在很大程度上仍不清楚。 最近，在纳瓦霍实施了一项名为家庭精神培育的生态预防计划 希普罗克社区通过随机对照试验。干预的重点是婴儿喂养做法 减少SSB摄入量。这项试验招募了母婴二人组，并收集了来自 3至12个月的婴儿，母婴混淆因素，以及1岁时的ECC状况。这 试验为纳瓦霍婴儿早期的纵向调查提供了一个无与伦比的机会 两个重要的具体目标：1)评估纳瓦霍婴儿口腔微生物群发育与以下方面的关系 母婴混杂因素及降糖干预对口腔的潜在影响 微生物组特征与龋病结局及2)纳瓦霍婴儿口腔微生物代谢组的研究 12个月龄时社区与ECC结局的相关性。 我们假设1)降糖干预可能会影响口腔微生物群的组成 在12个月龄时减少ECC结局，2)将会有 无龋纳瓦霍族婴儿口腔微生物组的发育变化和口腔病原学的变化 最终发展成龋齿的婴儿的微生物群落，3)龋齿的微生物群落- 12个月龄受影响组可能有较高水平的碳水化合物代谢相关代谢物 与无龋组相比，4)存在纳瓦霍族婴儿的龋病相关代谢物特征。 这项研究的目的是评估是否可以使用纳瓦霍婴儿的口腔微生物和代谢谱 通过未来的研究计划预测ECC并开发治疗干预措施。

PROJECT SUMMARY/ABSTRACT Early childhood caries (ECC) has devastating and long-lasting health consequences. These include higher healthcare costs, pain, infection, lower self-esteem, delayed speech development, poor performance in school, and subsequent poor oral and overall health outcomes as adults. The prevalence of ECC in children of American Indian (AI) families is considerably higher compared to all races in the United States, with ECC occurrence as early as one year of age. ECC and the closely related health disparity early childhood obesity (ECO), are critical for young AI children, especially in the Navajo community that has limited access to nutritious food and clean, safe drinking water. Diet is a crucial contributing factor to ECC and ECO, where high dietary sugar intake and early initiation of sugar-sweetened beverages (SSBs) before six months of age contribute significantly to both conditions in Navajo infants. Frequent sugar consumption drives the selection of cariogenic bacteria and associated metabolic activities within the oral microbiota that ultimately results in caries development. Acquisition and proliferation of cariogenic bacteria before two years of age have been associated with an increased risk of caries. However, the development of the oral microbiome and the impact of the sugar intake reduction on the pattern of microbiota in high-risk Navajo infants remain largely unknown. Recently, an ECO prevention program, called Family Spirit Nurture, was implemented in the Navajo Shiprock community through a randomized controlled trial. The intervention focused on infant feeding practices and SSB intake reduction. The trial enrolled mother-infant dyads and collected longitudinal oral samples from infants aged 3 to 12 months, maternal and child confounding factors, and ECC status at 1 year of age. This trial provided an unparalleled opportunity for the longitudinal investigation of Navajo infants at an early age with two important specific aims: 1) evaluate the developing oral microbiome of Navajo infants in relation to maternal and child confounding factors and the potential impact of the sugar reduction intervention on the oral microbiome profiles and caries outcomes and 2) investigate the metabolome of Navajo infants’ oral microbial communities in correlation with ECC outcomes at 12 months of age. We hypothesize that 1) the sugar reduction intervention may influence the oral microbiome composition toward non-cariogenic species and reduce ECC outcome at 12 months of age, 2) there would be developmental changes in the oral microbiome of caries-free Navajo infants and pathogenic shifts in the oral microbiome pattern for those infants who eventually develop caries, 3) Microbial communities of the caries- affected group at 12 months of age may have a higher level of carbohydrate metabolism-related metabolites compared to the caries-free group, and 4) there exists caries-related metabolite signatures of Navajo infants. The goal of this study is to evaluate if the oral microbial and metabolic profiles of Navajo infants could be used to predict ECC and to develop a therapeutic intervention through future research plans.