Gut microbiota mediates the inhibition of lymphopoiesis in dietary-restricted mice by suppressing glycolysis
Si Tao,
Yiting Wang,
Chenghui Yu,
Rongrong Qiu,
Yanjun Jiang,
Jie Jia,
Zhendong Tao,
Liu Zhang,
Bing Zou,
Duozhuang Tang
Affiliations
Si Tao
Jiangxi Key Laboratory of Clinical and Translational Cancer Research, Department of Oncology, The Second Affiliated Hospital of Nanchang University, Jiangxi, China
Yiting Wang
Department of Hematology, The Second Affiliated Hospital of Nanchang University, Jiangxi, China
Chenghui Yu
Department of Hematology, The Second Affiliated Hospital of Nanchang University, Jiangxi, China
Rongrong Qiu
Jiangxi Key Laboratory of Clinical and Translational Cancer Research, Department of Oncology, The Second Affiliated Hospital of Nanchang University, Jiangxi, China
Yanjun Jiang
Department of Hematology, The Second Affiliated Hospital of Nanchang University, Jiangxi, China
Jie Jia
Jiangxi Key Laboratory of Clinical and Translational Cancer Research, Department of Oncology, The Second Affiliated Hospital of Nanchang University, Jiangxi, China
Zhendong Tao
Department of Medical Laboratory Medicine, Jiangxi Province Hospital of Integrated Chinese & Western Medicine, Jiangxi, China
Liu Zhang
Intensive Care Unit, Peking University People’s Hospital, Beijing, China
Bing Zou
Jiangxi Key Laboratory of Clinical and Translational Cancer Research, Department of Oncology, The Second Affiliated Hospital of Nanchang University, Jiangxi, China
Duozhuang Tang
Department of Hematology, The Second Affiliated Hospital of Nanchang University, Jiangxi, China
Dietary restriction (DR) is one of the most robust interventions shown to extend health-span and remains on the forefront of anti-aging intervention studies, though conflicting results have been shown on its effect on lifespan both in rodents and primates. The severe inhibitory effects on the lymphoid lineage by DR remains one of its major negative downsides which reduces its overall beneficial effects on organismal health. Yet, the underlying mechanism of how DR suppresses the lymphoid system remains to be explored. Here, we show that antibiotic ablation of gut microbiota significantly rescued the inhibition of lymphopoiesis by DR. Interestingly, glycolysis in lymphocytes was significantly down-regulated in DR mice and pharmacological inhibition of glycolysis reverted this rescue effect of lymphopoiesis in DR mice with ablated gut microbiota. Furthermore, DR remarkably reconstructed gut microbiota with a significant increase in butyrate-producing bacterial taxa and in expression of But, a key gene involved in butyrate synthesis. Moreover, supplemental butyrate feeding in AL mice suppressed glycolysis in lymphoid cells and mimicked the inhibition of lymphopoiesis in AL mice. Together, our study reveals that gut microbiota mediates the inhibition on lymphopoiesis via down-regulation of glycolysis under DR conditions, which is associated with increased butyrate-synthesis. Our study uncovered a candidate that could potentially be targeted for ameliorating the negative effects of DR on lymphopoiesis, and therefore may have important implications for the wider application of DR and promoting healthy aging.
