Gut Microbiota-bile acid-progesterone Axis Mediates White Matter Injury in Infant Chronic Hypoxia

Abstract about our study:
Adverse child development has been implicated to the systemic chronic hypoxia since infant stage. Lately research suggested chronic hypoxia could disturb gut microbial balance which is essential to the brain development. However, mechanisms underlying such association remain largely unknown. Here, we found a strong correlation between severe brain immature and white matter injury (WMI) in infants underwent chronic hypoxia. Mechanistically, in a neonatal rat model of chronic hypoxia, we characterized severe brain immature and WMI with the deficits of motor coordination and learning. By combining 16S rRNA gene sequencing with untargeted metabolic profiling, we identified a reduction of intestinal Bacteroides and Parabacteroides under chronic hypoxia which causes the low production of progesterone, which is mainly due to the impair of the synthesis of progesterone by the accumulation of cholic acid. Administration of either Bacteroides, Parabacteroides or progesterone rescues the brain immature and WMI in the chronic hypoxia neonatal rats. Notably, the decreased levels of Bacteroides, Parabacteroides and progesterone were also discovered in infant patients with chronic hypoxia, implicating a universal crosstalk between the gut and brain across human and rat species under chronic hypoxia and shedding lights on the clinical therapeutics targeting the Bacteroides, Parabacteroides and their microbial metabolic product of progesterone for patients with systemic chronic hypoxia.
In this dataset, you could find all my original data of all figures. It is named by the number of the figure order.

关于本研究之摘要：儿童发育不良与自婴儿期起之系统性慢性缺氧密切相关。近期研究提出，慢性缺氧可能扰乱肠道微生物平衡，而此平衡对大脑发育至关重要。然而，此类关联背后的机制尚不清楚。本研究中发现，在经历慢性缺氧的婴儿中，严重的大脑未成熟与白质损伤（WMI）之间存在强烈的关联。在慢性缺氧的新生大鼠模型中，我们通过运动协调和学习能力的缺陷来表征严重的大脑未成熟和WMI。通过结合16S rRNA基因测序与无靶向代谢组学分析，我们发现在慢性缺氧条件下，肠道中的Bacteroides和Parabacteroides数量减少，导致孕酮产量降低，这主要归因于胆汁酸积累导致的孕酮合成受损。给予Bacteroides、Parabacteroides或孕酮的干预可以挽救慢性缺氧新生大鼠的大脑未成熟和WMI。值得注意的是，在慢性缺氧的婴儿患者中，也发现了Bacteroides、Parabacteroides和孕酮水平的降低，这表明在慢性缺氧状态下，人类与大鼠物种之间肠道与大脑存在普遍的交互作用，为针对系统性慢性缺氧患者靶向Bacteroides、Parabacteroides及其微生物代谢产物孕酮的临床治疗提供了启示。在本数据集中，您将找到所有原始数据的所有图像数据。这些数据以图像顺序编号命名。