Oligosaccharides from the seeds of Dolichos lablab L. promote gut microbial metabolite L-arginine production to alleviate cyclophosphamide-induced immunosuppression

Ben Liu^1,2Jiayi Jin¹Yuming Zhou²Zhipeng Shang^1,3Peng Meng⁴Maoru Du¹Feng Geng¹Xue Gao¹Feng Zhao^1,3Zhenguo Su²Xiaohong Pan^1,5*

• ¹School of Pharmacy, Binzhou Medical University, Yantai, China
• ²Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong Province, China
• ³The Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China, Yantai, Shandong Province, China
• ⁴Yantai Hospital of Traditional Chinese Medicine, Binzhou Medical University, Yantai, China
• ⁵Binzhou Medical University, Yantai Hospital of Traditional Chinese Medicine, Yantai, China

Dolichos lablab L. possesses significant nutritional and medicinal value. However, research on its oligosaccharides remains limited. This study investigated the effects of Dolichos lablab L. oligosaccharides on cyclophosphamide (CTX)-induced immunosuppression in mice. The crude oligosaccharides were purified to obtain a mixture named SRSV with an increased sugar content of 86%. The major components include sucrose, raffinose, stachyose, and verbascose at mass ratios of 19:16.8:50:14.2. SRSV (150mg/kg) preserves intestinal villi integrity, reverses CTX-induced immune organ atrophy, and restores the CD4+T/CD8+T ratio. It enhances bone marrow hematopoiesis, increases white blood cell and lymphocyte counts, and modulates blood TNF-α to ameliorate CTX-induced immunosuppression. 16S rRNA sequencing reveals that SRSV increases gut microbiota (GM) diversity, promoting beneficial bacteria like Ruminococcus, UBA1819, and Anaerofustis, while reducing pathogenic Atopobiaceae. Antibiotic-induced GM depletion significantly reduces SRSV’s protective effects, highlighting GM’s critical role. Metabolomics analysis identifies L-arginine as a key metabolite, enriched in the arginine biosynthesis pathway. Feeding L-arginine alone reproduces SRSV’s immune-protective effects in immunosuppressed mice. These findings indicate that SRSV has the potential to alleviate chemotherapy-induced immunosuppression and intestinal damage, positioning it as a promising immune enhancer and natural adjuvant for chemotherapy.