Department of Food Science, Faculty of Science, University of Copenhagen, DK-1958, Frederiksberg C, Denmark.
Section for Bioinformatics, Department of Health Technology, Technical University of Denmark, DK-2800, Lyngby, Denmark.
NPJ Biofilms Microbiomes. 2022 Jun 9;8(1):48. doi: 10.1038/s41522-022-00310-2.
The development of necrotizing enterocolitis (NEC), a life-threatening inflammatory bowel disease affecting preterm infants, is connected with gut microbiota dysbiosis. Using preterm piglets as a model for preterm infants we recently showed that fecal microbiota transplantation (FMT) from healthy suckling piglet donors to newborn preterm piglets decreased the NEC risk. However, in a follow-up study using donor stool from piglets recruited from another farm, this finding could not be replicated. This allowed us to study donor-recipient microbiota dynamics in a controlled model system with a clear difference in NEC phenotype. Preterm piglets (n = 38) were randomly allocated to receive control saline (CON), or rectal FMT using either the ineffective (FMT1) or the effective donor stool (FMT2). All animals were followed for four days before necropsy and gut pathological evaluation. Donor and recipient colonic gut microbiota (GM) were analyzed by 16 S rRNA gene amplicon sequencing and shotgun metagenomics. As expected, only FMT2 recipients were protected against NEC. Both FMT groups had shifted GM composition relative to CON, but FMT2 recipients had a higher lactobacilli relative abundance compared to FMT1. Limosilactobacillus reuteri and Lactobacillus crispatus strains of FMT recipients showed high phylogenetic similarity with their respective donors, indicating engraftment. Moreover, the FMT2 group had a higher lactobacilli replication rate and harbored specific glycosaminoglycan-degrading Bacteroides. In conclusion, subtle species-level donor differences translate to major changes in engraftment dynamics and the ability to prevent NEC. This could have implications for proper donor selection in future FMT trials for NEC prevention.
坏死性小肠结肠炎（NEC）是一种危及生命的炎症性肠病，影响早产儿，其发生与肠道微生物失调有关。我们最近使用早产仔猪作为早产儿模型进行的研究表明，来自健康哺乳仔猪供体的粪便微生物群移植（FMT）可降低新生早产仔猪的 NEC 风险。然而，在使用来自另一个农场仔猪供体粪便的后续研究中，这一发现无法得到复制。这使我们能够在具有明确 NEC 表型差异的受控模型系统中研究供体-受者微生物群动态。将早产仔猪（n=38）随机分配接受对照生理盐水（CON）或使用无效（FMT1）或有效供体粪便（FMT2）进行直肠 FMT。所有动物在安乐死后进行 4 天的肠道病理评估前进行跟踪。通过 16S rRNA 基因扩增子测序和 shotgun 宏基因组学分析供体和受体结肠肠道微生物群（GM）。正如预期的那样，只有 FMT2 受者能预防 NEC。与 CON 相比，FMT2 组和 FMT1 组的 GM 组成都发生了变化，但 FMT2 受者的乳杆菌相对丰度较高。FMT 受者的Limosilactobacillus reuteri和Lactobacillus crispatus 菌株与各自的供体具有高度的系统发育相似性，表明定植。此外，FMT2 组的乳杆菌复制率更高，并具有特定的糖胺聚糖降解拟杆菌。总之，供体之间的细微物种差异会导致定植动力学和预防 NEC 的能力发生重大变化。这可能对未来用于预防 NEC 的 FMT 试验中的适当供体选择产生影响。
