Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas (IATA-CSIC), Valencia, Spain.
Hospital Universitario Sant Joan de Reus, Tarragona, Spain.
Gut. 2015 Mar;64(3):406-17. doi: 10.1136/gutjnl-2014-306931. Epub 2014 Jun 17.
Intestinal dysbiosis has been associated with coeliac disease (CD), but whether the alterations are cause or consequence of the disease is unknown. This study investigated whether the human leukocyte antigen (HLA)-DQ2 genotype is an independent factor influencing the early gut microbiota composition of healthy infants at family risk of CD.
As part of a larger prospective study, a subset (n=22) of exclusively breastfed and vaginally delivered infants with either high genetic risk (HLA-DQ2 carriers) or low genetic risk (non-HLA-DQ2/8 carriers) of developing CD were selected from a cohort of healthy infants with at least one first-degree relative with CD. Infant faecal microbiota was analysed by 16S rRNA gene pyrosequencing and real time quantitative PCR.
Infants with a high genetic risk had significantly higher proportions of Firmicutes and Proteobacteria and lower proportions of Actinobacteria compared with low-risk infants. At genus level, high-risk infants had significantly less Bifidobacterium and unclassified Bifidobacteriaceae proportions and more Corynebacterium, Gemella, Clostridium sensu stricto, unclassified Clostridiaceae, unclassified Enterobacteriaceae and Raoultella proportions. Quantitative real time PCR also revealed lower numbers of Bifidobacterium species in infants with high genetic risk than in those with low genetic risk. In high-risk infants negative correlations were identified between Bifidobacterium species and several genera of Proteobacteria (Escherichia/Shigella) and Firmicutes (Clostridium).
The genotype of infants at family risk of developing CD, carrying the HLA-DQ2 haplotypes, influences the early gut microbiota composition. This finding suggests that a specific disease-biased host genotype may also select for the first gut colonisers and could contribute to determining disease risk.
肠菌群失调与乳糜泻（CD）有关，但这些改变是疾病的原因还是后果尚不清楚。本研究旨在探讨人类白细胞抗原（HLA）-DQ2 基因型是否是影响 CD 家族高风险健康婴儿早期肠道微生物群组成的独立因素。
作为一项更大的前瞻性研究的一部分，从一个至少有一个一级亲属患有 CD 的健康婴儿队列中，选择了一组（n=22）纯母乳喂养和阴道分娩的婴儿，他们具有 CD 的高遗传风险（HLA-DQ2 携带者）或低遗传风险（非 HLA-DQ2/8 携带者）。采用 16S rRNA 基因焦磷酸测序和实时定量 PCR 分析婴儿粪便微生物群。
高遗传风险婴儿的厚壁菌门和变形菌门比例显著高于低遗传风险婴儿，放线菌门比例显著低于低遗传风险婴儿。在属水平上，高遗传风险婴儿双歧杆菌和未分类双歧杆菌科的比例显著较低，而 Corynebacterium、Gemella、Clostridium sensu stricto、未分类 Clostridiaceae、未分类 Enterobacteriaceae 和 Raoultella 的比例显著较高。定量实时 PCR 还显示，高遗传风险婴儿的双歧杆菌属数量低于低遗传风险婴儿。在高遗传风险婴儿中，双歧杆菌属与几种变形菌属（Escherichia/Shigella）和厚壁菌门（Clostridium）之间存在负相关。
具有 HLA-DQ2 单体型的 CD 家族高风险婴儿的基因型影响早期肠道微生物群组成。这一发现表明，特定的疾病偏向宿主基因型也可能选择最初的肠道定植菌，并可能有助于确定疾病风险。
