The Association between Infant Colic and the Multi-Omic Composition of Human Milk

Infant colic is a common condition with unclear biologic underpinnings and limited treatment options. We hypothesized that complex molecular networks within human milk (i.e., microbes, micro-ribonucleic acids (miRNAs), cytokines) would contribute to colic risk, while controlling for medical, social,...

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Main Authors: Desirae Chandran, Kaitlyn Warren, Daniel McKeone, Steven D. Hicks
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/13/3/559
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author Desirae Chandran
Kaitlyn Warren
Daniel McKeone
Steven D. Hicks
author_facet Desirae Chandran
Kaitlyn Warren
Daniel McKeone
Steven D. Hicks
author_sort Desirae Chandran
collection DOAJ
description Infant colic is a common condition with unclear biologic underpinnings and limited treatment options. We hypothesized that complex molecular networks within human milk (i.e., microbes, micro-ribonucleic acids (miRNAs), cytokines) would contribute to colic risk, while controlling for medical, social, and nutritional variables. This hypothesis was tested in a cohort of 182 breastfed infants, assessed with a modified Infant Colic Scale at 1 month. RNA sequencing was used to interrogate microbial and miRNA features. Luminex assays were used to measure growth factors and cytokines. Milk from mothers of infants with colic (<i>n</i> = 28) displayed higher levels of <i>Staphylococcus</i> (adj. <i>p</i> = 0.038, <i>d</i> = 0.30), miR-224-3p (adj. <i>p</i> = 0.023, <i>d</i> = 0.33), miR-125b-5p (adj. <i>p</i> = 0.028, <i>d</i> = 0.29), let-7a-5p (adj. <i>p</i> = 0.028, <i>d</i> = 0.27), and miR-205-5p (adj. <i>p</i> = 0.029, <i>d</i> = 0.26) compared to milk from non-colic mother–infant dyads (<i>n</i> = 154). Colic symptom severity was directly associated with milk hepatocyte growth factor levels (<i>R</i> = 0.21, <i>p</i> = 0.025). A regression model involving let-7a-5p, miR-29a-3p, and <i>Lactobacillus</i> accurately modeled colic risk (<i>X</i><sup>2</sup> = 16.7, <i>p</i> = 0.001). Molecular factors within human milk may impact colic risk, and provide support for a dysbiotic/inflammatory model of colic pathophysiology.
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spelling doaj.art-eb4f2a95924b49648e237b439e2b24872023-11-17T09:53:00ZengMDPI AGBiomolecules2218-273X2023-03-0113355910.3390/biom13030559The Association between Infant Colic and the Multi-Omic Composition of Human MilkDesirae Chandran0Kaitlyn Warren1Daniel McKeone2Steven D. Hicks3Department of Pediatrics, Penn State College of Medicine, Hershey, PA 17033, USADepartment of Pediatrics, Penn State College of Medicine, Hershey, PA 17033, USADepartment of Pediatrics, Penn State College of Medicine, Hershey, PA 17033, USADepartment of Pediatrics, Penn State College of Medicine, Hershey, PA 17033, USAInfant colic is a common condition with unclear biologic underpinnings and limited treatment options. We hypothesized that complex molecular networks within human milk (i.e., microbes, micro-ribonucleic acids (miRNAs), cytokines) would contribute to colic risk, while controlling for medical, social, and nutritional variables. This hypothesis was tested in a cohort of 182 breastfed infants, assessed with a modified Infant Colic Scale at 1 month. RNA sequencing was used to interrogate microbial and miRNA features. Luminex assays were used to measure growth factors and cytokines. Milk from mothers of infants with colic (<i>n</i> = 28) displayed higher levels of <i>Staphylococcus</i> (adj. <i>p</i> = 0.038, <i>d</i> = 0.30), miR-224-3p (adj. <i>p</i> = 0.023, <i>d</i> = 0.33), miR-125b-5p (adj. <i>p</i> = 0.028, <i>d</i> = 0.29), let-7a-5p (adj. <i>p</i> = 0.028, <i>d</i> = 0.27), and miR-205-5p (adj. <i>p</i> = 0.029, <i>d</i> = 0.26) compared to milk from non-colic mother–infant dyads (<i>n</i> = 154). Colic symptom severity was directly associated with milk hepatocyte growth factor levels (<i>R</i> = 0.21, <i>p</i> = 0.025). A regression model involving let-7a-5p, miR-29a-3p, and <i>Lactobacillus</i> accurately modeled colic risk (<i>X</i><sup>2</sup> = 16.7, <i>p</i> = 0.001). Molecular factors within human milk may impact colic risk, and provide support for a dysbiotic/inflammatory model of colic pathophysiology.https://www.mdpi.com/2218-273X/13/3/559<i>Lactobacillus</i>colicbreastmilkmicrobiomecytokinesmicroRNA
spellingShingle Desirae Chandran
Kaitlyn Warren
Daniel McKeone
Steven D. Hicks
The Association between Infant Colic and the Multi-Omic Composition of Human Milk
Biomolecules
<i>Lactobacillus</i>
colic
breastmilk
microbiome
cytokines
microRNA
title The Association between Infant Colic and the Multi-Omic Composition of Human Milk
title_full The Association between Infant Colic and the Multi-Omic Composition of Human Milk
title_fullStr The Association between Infant Colic and the Multi-Omic Composition of Human Milk
title_full_unstemmed The Association between Infant Colic and the Multi-Omic Composition of Human Milk
title_short The Association between Infant Colic and the Multi-Omic Composition of Human Milk
title_sort association between infant colic and the multi omic composition of human milk
topic <i>Lactobacillus</i>
colic
breastmilk
microbiome
cytokines
microRNA
url https://www.mdpi.com/2218-273X/13/3/559
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