Nature Communications ( IF 14.7 ) Pub Date : 2024-07-23 , DOI: 10.1038/s41467-024-50282-4 Kelsey E Johnson 1 , Nelmary Hernandez-Alvarado 2 , Mark Blackstad 2 , Timothy Heisel 2 , Mattea Allert 1 , David A Fields 3 , Elvira Isganaitis 4 , Katherine M Jacobs 5 , Dan Knights 6, 7 , Eric F Lock 8 , Michael C Rudolph 9 , Cheryl A Gale 2 , Mark R Schleiss 2 , Frank W Albert 1 , Ellen W Demerath 10 , Ran Blekhman 11
Human cytomegalovirus (CMV) is a highly prevalent herpesvirus that is often transmitted to the neonate via breast milk. Postnatal CMV transmission can have negative health consequences for preterm and immunocompromised infants, but any effects on healthy term infants are thought to be benign. Furthermore, the impact of CMV on the composition of the hundreds of bioactive factors in human milk has not been tested. Here, we utilize a cohort of exclusively breastfeeding full-term mother-infant pairs to test for differences in the milk transcriptome and metabolome associated with CMV, and the impact of CMV in breast milk on the infant gut microbiome and infant growth. We find upregulation of the indoleamine 2,3-dioxygenase (IDO) tryptophan-to-kynurenine metabolic pathway in CMV+ milk samples, and that CMV+ milk is associated with decreased Bifidobacterium in the infant gut. Our data indicate two opposing CMV-associated effects on infant growth; with kynurenine positively correlated, and CMV viral load negatively correlated, with infant weight-for-length at 1 month of age. These results suggest CMV transmission, CMV-related changes in milk composition, or both may be modulators of full-term infant development.
中文翻译:
母乳中的人类巨细胞病毒与牛奶成分、婴儿肠道微生物组和生长有关
人巨细胞病毒 (CMV) 是一种高度流行的疱疹病毒,通常通过母乳传播给新生儿。出生后 CMV 传播可能对早产儿和免疫功能低下的婴儿产生负面的健康影响,但对健康足月儿的任何影响都被认为是良性的。此外,CMV 对母乳中数百种生物活性因子组成的影响尚未得到测试。在这里,我们利用一组纯母乳喂养足月母婴对来测试与 CMV 相关的牛奶转录组和代谢组的差异,以及母乳中 CMV 对婴儿肠道微生物组和婴儿生长的影响。我们发现 CMV + 牛奶样品中吲哚胺 2,3-双加氧酶 (IDO) 色氨酸到犬尿氨酸代谢途径的上调,并且 CMV + 牛奶与婴儿肠道中双歧杆菌的减少有关。我们的数据表明 CMV 对婴儿生长的两种相反的影响;犬尿氨酸与犬尿氨酸呈负相关,CMV 病毒载量与 1 月龄婴儿身长别体重呈负相关。这些结果表明,CMV 传播、CMV 相关的乳汁成分变化或两者兼而有之可能是足月婴儿发育的调节因素。