Alginate oligosaccharides improve germ cell development and testicular microenvironment to rescue busulfan disrupted spermatogenesis. Zhao Yong,Zhang Pengfei,Ge Wei,Feng Yanni,Li Lan,Sun Zhongyi,Zhang Hongfu,Shen Wei Theranostics : Busulfan is currently an indispensable anti-cancer drug, particularly for children, but the side effects on male reproduction are so serious that critical drug management is needed to minimize any negative impact. Meanwhile, alginate oligosaccharides (AOS) are natural products with many consequent advantages, that have attracted a great deal of pharmaceutical attention. In the current investigation, we performed single-cell RNA sequencing on murine testes treated with busulfan and/or AOS to define the mitigating effects of AOS on spermatogenesis at the single cell level. : Testicular cells () were examined by single cell RNA sequencing analysis, histopathological analysis, immunofluorescence staining, and Western blotting. Testes samples () underwent RNA sequencing analysis. Blood and testicular metabolomes were determined by liquid chromatography-mass spectrometry (LC/MS). : We found that AOS increased murine sperm concentration and motility, and rescued busulfan disrupted spermatogenesis through improving (i) the proportion of germ cells, (ii) gene expression important for spermatogenesis, and (iii) transcriptional factors . Furthermore, AOS promoted the expression of genes important for spermatogenesis Finally, our results showed that AOS improved blood and testis metabolomes as well as the gut microbiota to support the recovery of spermatogenesis. : AOS could be used to improve fertility in patients undergoing chemotherapy and to combat other factors that induce infertility in humans. 10.7150/thno.43189

Microbiota from alginate oligosaccharide-dosed mice successfully mitigated small intestinal mucositis. Zhang Pengfei,Liu Jing,Xiong Bohui,Zhang Cong,Kang Beining,Gao Yishan,Li Zengkuan,Ge Wei,Cheng Shunfeng,Hao Yanan,Shen Wei,Yu Shuai,Chen Liang,Tang Xiangfang,Zhao Yong,Zhang Hongfu Microbiome BACKGROUND:The increasing incidence of cancer and intestinal mucositis induced by chemotherapeutics are causing worldwide concern. Many approaches such as fecal microbiota transplantation (FMT) have been used to minimize mucositis. However, it is still unknown whether FMT from a donor with beneficial gut microbiota results in more effective intestinal function in the recipient. Recently, we found that alginate oligosaccharides (AOS) benefit murine gut microbiota through increasing "beneficial" microbes to rescue busulfan induced mucositis. RESULTS:In the current investigation, FMT from AOS-dosed mice improved small intestine function over FMT from control mice through the recovery of gene expression and an increase in the levels of cell junction proteins. FMT from AOS-dosed mice showed superior benefits over FMT from control mice on recipient gut microbiotas through an increase in "beneficial" microbes such as Leuconostocaceae and recovery in blood metabolome. Furthermore, the correlation of gut microbiota and blood metabolites suggested that the "beneficial" microbe Lactobacillales helped with the recovery of blood metabolites, while the "harmful" microbe Mycoplasmatales did not. CONCLUSION:The data confirm our hypothesis that FMT from a donor with superior microbes leads to a more profound recovery of small intestinal function. We propose that gut microbiota from naturally produced AOS-treated donor may be used to prevent small intestinal mucositis induced by chemotherapeutics or other factors in recipients. Video Abstract. 10.1186/s40168-020-00886-x