Data_Sheet_3_Malnourishment affects gene expression along the length of the small intestine.xlsx

Malnourishment is a risk factor for childhood mortality, jeopardizing the health of children by aggravating pneumonia/acute respiratory infections and diarrheal diseases. Malnourishment causes morphophysiological changes resulting in stunting and wasting that have long-lasting consequences such as cognitive deficit and metabolic dysfunction. Using a pig model of malnutrition, the interplay between the phenotypic data displayed by the malnourished animals, the gene expression pattern along the intestinal tract, microbiota composition of the intestinal contents, and hepatic metabolite concentrations from the same animals were correlated using a multi-omics approach. Samples from the duodenum, jejunum, and ileum of malnourished (protein and calorie-restricted diet) and full-fed (no dietary restrictions) piglets were subjected to RNA-seq. Gene co-expression analysis and phenotypic correlations were made with WGCNA, while the integration of transcriptome with microbiota composition and the hepatic metabolite profile was done using mixOmics. Malnourishment caused changes in tissue gene expression that influenced energetic balance, cell proliferation, nutrient absorption, and response to stress. Repression of antioxidant genes, including glutathione peroxidase, in coordination with induction of metal ion transporters corresponded to the hepatic metabolite changes. These data indicate oxidative stress in the intestine of malnourished animals. Furthermore, several of the phenotypes displayed by these animals could be explained by changes in gene expression.

营养不良是儿童死亡的危险因素，可通过加重肺炎、急性呼吸道感染与腹泻性疾病的病情，损害儿童健康。营养不良会引发形态生理变化，进而导致生长迟缓与消瘦，并带来认知缺陷、代谢功能障碍等长期后遗症。本研究采用营养不良猪模型，通过多组学方法，对营养不良仔猪的表型数据、肠道全段基因表达模式、肠道内容物菌群组成以及同一受试仔猪的肝脏代谢物浓度之间的相互关联进行分析。研究对营养不良组（饲喂蛋白与热量限制日粮）与自由采食组（无饮食限制）仔猪的十二指肠、空肠及回肠样本开展了RNA测序（RNA-seq）。采用加权基因共表达网络分析（WGCNA）进行基因共表达分析与表型关联分析，同时使用mixOmics工具整合转录组、菌群组成与肝脏代谢物谱数据。营养不良可引发组织基因表达变化，进而影响能量平衡、细胞增殖、营养吸收与应激响应。抗氧化基因（包括谷胱甘肽过氧化物酶）的表达抑制，与金属离子转运蛋白的表达诱导协同发生，与肝脏代谢物变化相契合。上述数据表明，营养不良个体的肠道存在氧化应激。此外，受试仔猪所表现出的多种表型可通过基因表达变化得到合理解释。