Huang Wei, Sha Yuzhu, Chen Qianling, Chen Xiaowei, Gao Min, Liu Xiu, He Yapeng, Gao Xu, Hu Jiang, Wang Jiqing, Li Shaobin, Hao Zhiyun, He Yanyu
College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, 730070, China.
School of Fundamental Sciences, Massey University, Palmerston North, 4410, New Zealand.
BMC Vet Res. 2025 May 26;21(1):373. doi: 10.1186/s12917-025-04823-8.
The gut-brain axis is regarded as the "second brain" of the host. Gut microbiota and their metabolites affect intestinal homeostasis, function, and phenotype by regulating bidirectional communication between the gut and brain. This serves as a vital strategy for understanding how gut microbiota regulate nutrient metabolism and adaptability in animals. This study explored the metabolic mechanisms through which Tibetan sheep adapt to high-altitude environments via the rumen microbiota-gut-brain axis across different phenological periods (returning-green period, fresh grass period and withered grass period). By analyzing metabolic indicators, neurotransmitters, and gene and protein expression in serum, rumen, adipose, and hypothalamic tissues, we discovered that energy metabolism markers (creatine kinase, lactate dehydrogenase, glucose) and immunoglobulins (IgG, IgM) in the serum were significantly elevated during the fresh grass period (P < 0.05). In contrast, thyroid hormones T3 and T4 were at higher levels during the returning-green period (P < 0.05). The density of rumen fiber-degrading bacteria was higher during the returning-green period (P < 0.05). Meanwhile, the densities of Butyrivibrio fibrisolvens, Selenomonas ruminantium, and Treponema bryantii microbiota significantly during the fresh grass period and were positively correlated with isovaleric acid concentration (P < 0.05). Neurotransmitters (5-HT, DOPAC, 5-HIAA, and NE) were significantly elevated in both the rumen epithelium and hypothalamus during the fresh grass period (P < 0.05). The analysis of the cAMP-PKA-pCREB pathway showed that the genes and proteins of UCP1, PKA, and CREB1 were highly expressed in adipose tissue during the fresh grass and withered grass periods, and there significant negative correlations to specific microbiota (P < 0.05). In summary, Tibetan sheep adapt to high-altitude environments through the rumen microbiota-gut-brain axis, regulating metabolic and neurotransmitter changes to establish a unique metabolic adaptation mechanism.
肠-脑轴被视为宿主的“第二大脑”。肠道微生物群及其代谢产物通过调节肠道与大脑之间的双向通讯来影响肠道内环境稳定、功能和表型。这是理解肠道微生物群如何调节动物营养代谢和适应性的重要策略。本研究通过瘤胃微生物群-肠-脑轴，探讨了藏羊在不同物候期（返青期、青草期和枯草期）适应高海拔环境的代谢机制。通过分析血清、瘤胃、脂肪和下丘脑组织中的代谢指标、神经递质以及基因和蛋白质表达，我们发现青草期血清中的能量代谢标志物（肌酸激酶、乳酸脱氢酶、葡萄糖）和免疫球蛋白（IgG、IgM）显著升高（P < 0.05）。相比之下，返青期甲状腺激素T3和T4水平较高（P < 0.05）。返青期瘤胃纤维降解菌的密度较高（P < 0.05）。同时，在青草期，溶纤维丁酸弧菌、反刍月形单胞菌和布氏密螺旋体微生物群的密度显著增加，且与异戊酸浓度呈正相关（P < 0.05）。青草期瘤胃上皮和下丘脑中的神经递质（5-羟色胺、二羟基苯乙酸、5-羟吲哚乙酸和去甲肾上腺素）显著升高（P < 0.05）。对cAMP-PKA-pCREB通路的分析表明，UCP1、PKA和CREB1的基因和蛋白质在青草期和枯草期的脂肪组织中高表达，且与特定微生物群存在显著负相关（P < 0.05）。综上所述，藏羊通过瘤胃微生物群-肠-脑轴适应高海拔环境，调节代谢和神经递质变化，建立独特的代谢适应机制。
