<b>Multi-omics analysis of gut liver axis reveals key microbial involved in inflammatory injury in malnutrition trail goat kids models</b>

Global healthcare system has made considerable advancements in addressing malnutrition stemming from imbalances in nutrient substrates. However, the association between non-nutrient substrates deficient malnutrition and the inflammatory status alongside the underlying pathological mechanisms of the body remains elusive. To elucidate the pathogenic factors and mechanisms related to the intestine, we delved into the intricate interplay between the gut microbiota of low-weight goat kids and serum proinflammatory cytokines, antioxidant enzyme activity indicators, as well as the expression of genes in gut-liver axis inflammation, thereby pinpointing the pathogenic microbiota involved. Our investigation revealed significant increases in systemic inflammation coupled with a decline in antioxidant capacity among low-weight goat kids, an occurrence intricately linked to intestinal inflammation. The exaggerated intestinal response to inflammatory stimuli primarily manifests in colon as opposed to the jejunum. We established that the intestinal inflammatory milieu is significantly influenced by the distinctive microbiota composition of the colon, which is correlated with an upregulation of inflammatory gene expression and IL-6 emerged as a core inflammatory gene in the liver. Our study emphasized a substantial enrichment of Escherichia-Shigella, Campylobacter, and Alistipes within the colon of low-weight goat kids, further supported by correlation analyses affirming the association between the expression of genes linked to gut-liver axis inflammation and the abundance of pathogenic microbiota. These pathogenic microbiotas stand as a hallmark feature signifying the onset of inflammation within malnutrition. These findings provide a theoretical foundation and novel pathway for future interventions aimed at targeting pathogenic microbiota to reduce the overuse of broad-spectrum antibiotics.全球医疗体系在应对因营养底物（nutrient substrates）失衡引发的营养不良方面已取得长足进展。然而，非营养底物（non-nutrient substrates）缺乏型营养不良与机体炎症状态及其潜在病理机制之间的关联仍不明确。为阐明与肠道相关的致病因素及机制，本研究深入探究了低体重山羊羔肠道菌群与血清促炎细胞因子、抗氧化酶活性指标以及肠-肝轴（gut-liver axis）炎症相关基因表达之间的复杂相互作用，进而明确了所涉及的致病菌群。本研究发现，低体重山羊羔存在显著的全身炎症反应升高与抗氧化能力下降，这一现象与肠道炎症密切相关。机体对炎症刺激的过度肠道反应主要表现于结肠，而非空肠。本研究证实，肠道炎症微环境显著受结肠独特菌群组成的影响，而该菌群组成与炎症基因表达上调相关，且白细胞介素6（IL-6，Interleukin 6）成为肝脏中的核心炎症基因。本研究明确，低体重山羊羔结肠内埃希氏菌-志贺氏菌属（Escherichia-Shigella）、弯曲杆菌属（Campylobacter）与另枝菌属（Alistipes）显著富集，相关性分析进一步证实，肠-肝轴炎症相关基因的表达与致病菌群丰度之间存在关联。这些致病菌群可作为营养不良相关炎症发生的标志性特征。本研究结果为未来以靶向致病菌群、减少广谱抗生素过度使用为目标的干预措施提供了理论基础与全新思路。