High engraftment capacity of frozen ready-to-use human fecal transplants assessed in germ-free mice

The number of indications for fecal microbiota transplantation is expected to rise, thus increasing the needs for production of readily available frozen or freeze-dried transplants. Using shotgun metagenomics, we investigated the capacity of two innovative human fecal transplants prepared in maltodextrin-trehalose solutions (abbreviated MD and TR), to colonize a germ-free born mouse model. Gavage with frozen-thawed MD or TR suspensions gave the taxonomic profiles of mouse feces that best resembled those obtained with the fresh inoculum (Spearman correlations based on relative abundances of metagenomic species around 0.80 and 0.75 for MD and TR respectively), while engraftment capacity of defrosted NaCl transplants most diverged (Spearman correlations around 0.63). Engraftment of members of the family Lachnospiraceae and Ruminoccocaceae was the most challenging in all groups of mice, being improved with MD and TR transplants compared to NaCl, but still lower than with the fresh preparation. Improvement of engraftment of this important group in maintaining health represents a challenge that could benefit from further research on fecal transplant manufacturing.

粪菌移植（fecal microbiota transplantation）的适应证数量预计将持续增长，进而对便捷可得的冷冻或冻干粪菌移植制剂的生产需求持续攀升。本研究采用霰弹枪宏基因组学（shotgun metagenomics）技术，探究了两种以麦芽糊精-海藻糖溶液（缩写为MD和TR）配制的新型人源粪菌移植制剂在无菌小鼠模型中的定植能力。经灌胃给予冻融后的MD或TR悬浮液后，小鼠粪便的分类学谱与新鲜接种物所得结果最为相似：基于宏基因组物种相对丰度的斯皮尔曼相关性，MD组约为0.80，TR组约为0.75；而复溶的氯化钠（NaCl）对照移植制剂的定植能力则与新鲜接种物差异最大，斯皮尔曼相关性约为0.63。毛螺菌科（Lachnospiraceae）与瘤胃球菌科（Ruminococcaceae）成员的定植在所有受试小鼠组别中均为最难实现的环节；与NaCl制剂相比，MD与TR制剂可改善这两类菌群的定植效果，但仍不及新鲜制备的移植制剂。优化这类对维持机体健康至关重要的菌群的定植效果，仍是一项亟待解决的挑战，该问题可通过针对粪菌移植制剂生产工艺的深入研究得到改善。