Department of Pediatrics, Section of Nutrition, University of Colorado School of Medicine, Aurora, CO, United States.
Microbiome and Metabolism Research Unit (MMRU), United States Department of Agriculture - Agricultural Research Service (USDA-ARS), Southeast Area, Little Rock, AR, United States.
Front Endocrinol (Lausanne). 2024 Oct 4;15:1423464. doi: 10.3389/fendo.2024.1423464. eCollection 2024.
Maternal undernutrition is the most common cause of fetal growth restriction (FGR) worldwide. FGR increases morbidity and mortality during infancy, as well as contributes to adult-onset diseases including obesity and type 2 diabetes. The role of the maternal or offspring microbiome in growth outcomes following FGR is not well understood.
FGR was induced by 30% maternal calorie restriction (CR) during the second half of gestation in C57BL/6 mice. Pup weights were obtained on day of life 0, 1, and 7 and ages 3, 4 and 16 weeks. Fecal pellets were collected from pregnant dams at gestational day 18.5 and from offspring at ages 3 and 4 weeks of age. Bacterial genomic DNA was used for amplification of the V4 variable region of the 16S rRNA gene. Multivariable associations between maternal CR and taxonomic abundance were assessed using the MaAsLin2 package. Associations between microbial taxa and offspring outcomes were performed using distance-based redundancy analysis and Pearson correlations.
FGR pups weighed about 20% less than controls. Beta but not alpha diversity differed between control and CR dam microbiomes. CR dams had lower relative abundance of , , and , and increased relative abundance of and . Control and FGR offspring microbiota differed by beta diversity at ages 3 and 4 weeks. At 3 weeks, FGR offspring had decreased relative abundance of and and increased relative abundance of and . At 4 weeks, FGR animals had decreased relative abundance of , , , and , among others, and increased relative abundance of , , and . Maternal abundance was positively associated with offspring weight. abundance at age 3 and 4 weeks was negatively associated with adult weight.
We demonstrate gut microbial dysbiosis in pregnant dams and offspring at two timepoints following maternal calorie restriction. Additional research is needed to test for functional roles of the microbiome in offspring growth outcomes.
母体营养不良是全球胎儿生长受限（FGR）最常见的原因。FGR 会增加婴儿期的发病率和死亡率，并导致成年后发病，包括肥胖和 2 型糖尿病。母体或后代微生物组在 FGR 后生长结果中的作用尚不清楚。
在 C57BL/6 小鼠妊娠后半期通过 30%的母体热量限制（CR）诱导 FGR。在出生第 0、1 和 7 天以及 3、4 和 16 周时获得幼仔体重。在妊娠第 18.5 天和幼仔 3 和 4 周龄时收集孕鼠和幼仔的粪便颗粒。使用细菌基因组 DNA 扩增 16S rRNA 基因的 V4 可变区。使用 MaAsLin2 包评估母体 CR 与分类丰度之间的多变量关联。使用基于距离的冗余分析和 Pearson 相关性分析微生物类群与后代结果之间的关联。
FGR 幼仔的体重比对照组低约 20%。β多样性而不是 α多样性在对照和 CR 母鼠微生物组之间存在差异。CR 母鼠的相对丰度较低， 和 ，相对丰度增加 和 。在 3 和 4 周龄时，对照和 FGR 后代的微生物群存在β多样性差异。在 3 周龄时，FGR 后代的 和 相对丰度降低， 和 相对丰度增加。在 4 周龄时，FGR 动物的 和 等相对丰度降低， 和 等相对丰度增加。母鼠 丰度与后代体重呈正相关。3 周和 4 周时的 丰度与成年体重呈负相关。
我们证明了母体热量限制后两个时间点的孕鼠和后代肠道微生物失调。需要进一步的研究来测试微生物组在后代生长结果中的功能作用。
