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Updated: Jun 4, 2025
A Method for Targeted 16S Sequencing of Human Milk Samples
Published on: March 23, 2018
Network-Based Bioinformatics Highlights Broad Importance of Human Milk Hyaluronan
Kathryn Y Burge1, Hua Zhong1, Adam P Wilson1
1Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Insights
Human milk
Area of Science:
- Neonatal development
- Gastroenterology
- Immunology
Background:
- Human milk (HM) contains bioactive factors crucial for infant gut development.
- Hyaluronan (HA), a glycosaminoglycan in HM, is linked to protection against necrotizing enterocolitis (NEC).
- Specific molecular mechanisms of HA's protective effects on the neonatal ileum are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms by which 35 kDa hyaluronan (HA35) promotes intestinal maturation.
- To investigate HA35's impact on ileal cell populations and signaling pathways in neonatal mice.
- To identify potential pathways through which HA35 confers protection against NEC.
Main Methods:
- CD-1 mouse pups were administered HA35 or vehicle control from postnatal day 7 to 14.
- Bulk RNA sequencing of ileal transcriptomes was performed.
- Network and functional analyses, including gene set enrichment and pathway analyses, were utilized.
- Cell deconvolution was applied to analyze changes in ileal cell composition.
Main Results:
- HA35 treatment led to distinct transcriptomic profiles compared to controls.
- Cell deconvolution indicated increased proportions of stromal, Paneth, and mature enterocyte/progenitor cells.
- Key pro-growth and differentiation pathways were upregulated, including oxidative stress response and mTOR signaling.
- Apoptotic signaling pathways were downregulated in HA35-treated pups.
Conclusions:
- HA35 promotes ileal maturation in neonatal mice by modulating cell populations and signaling pathways.
- Upregulation of antioxidant, growth, and differentiation pathways, alongside downregulation of apoptosis, are key mechanisms.
- These findings suggest HA35's potential as a therapeutic agent against NEC in preterm infants.
Abstract:
Human milk (HM) is rich in bioactive factors promoting postnatal small intestinal development and maturation of the microbiome. HM is also protective against necrotizing enterocolitis (NEC), a devastating inflammatory condition predominantly affecting preterm infants. The HM glycosaminoglycan, hyaluronan (HA), is present at high levels in colostrum and early milk. Our group has demonstrated that HA with a molecular weight of 35 kDa (HA35) promotes maturation of the murine neonatal intestine and protects against two distinct models of NEC. However, the molecular mechanisms underpinning HA35-induced changes in the developing ileum are unclear. CD-1 mouse pups were treated with HA35 or vehicle control daily, from P7 to P14, and we used network and functional analyses of bulk RNA-seq ileal transcriptomes to further characterize molecular mechanisms through which HA35 likely influences intestinal maturation. HA35-treated pups separated well by principal component analysis, and cell deconvolution revealed increases in stromal, Paneth, and mature enterocyte and progenitor cells in HA35-treated pups. Gene set enrichment and pathway analyses demonstrated upregulation in key processes related to antioxidant and growth pathways, such as nuclear factor erythroid 2-related factor-mediated oxidative stress response, hypoxia inducible factor-1 alpha, mechanistic target of rapamycin, and downregulation of apoptotic signaling. Collectively, pro-growth and differentiation signals induced by HA35 may present novel mechanisms by which this HM bioactive factor may protect against NEC.
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