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Human milk small extracellular vesicles elicit changes in inflammatory response in infant human intestinal enteroids
Kacie D Waiters1, Anthony S Peidl1, Hailey A McAndrew1
1Center for Nuclear Receptors & Cell Signaling, Department of Biology & Biochemistry, University of Houston, Houston, TX, 77204, USA.
Insights
Human milk extracellular vesicles (HMEVs) show potential in preventing infant gastrointestinal inflammation. These HMEVs reduce inflammatory gene expression and protect the intestinal barrier in human models.
Area of Science:
- Biomedical Science
- Neonatal Research
- Extracellular Vesicle Biology
Background:
- Human milk (HM) is crucial for infant nutrition and preventing necrotizing enterocolitis (NEC) in preterm infants.
- HM-derived small extracellular vesicles (HMEVs) show anti-inflammatory effects in animal models, but human data is limited.
Purpose of the Study:
- To investigate the effects of human milk extracellular vesicles (HMEVs) on the human intestinal epithelium.
- To determine if HMEVs can mitigate inflammation and barrier dysfunction in human intestinal models.
Main Methods:
- HMEVs were isolated and characterized from different human milk samples.
- Human intestinal enteroids (HIEs) derived from neonates were exposed to HMEVs.
- Gene expression and barrier function were assessed after HMEV exposure and inflammatory challenge.
Main Results:
- HMEV exposure induced gene signatures associated with reduced inflammation, including NFkB-driven TNFα signaling.
- Pre-exposure to HMEVs decreased the magnitude of EGTA- and TNF-induced barrier disruption in HIEs.
- HMEVs demonstrated a protective effect on the human intestinal epithelial barrier.
Conclusions:
- HMEVs induce significant transcriptional and functional changes in the human intestinal epithelium.
- HMEVs hold promise as a therapeutic agent for preventing and treating neonatal gastrointestinal inflammatory diseases.
- This foundational research supports future development of HMEV-based therapeutics.
Abstract:
Human milk (HM) is the key nutritional source for infants and the most effective preventative approach against serious gastrointestinal inflammatory diseases like necrotizing enterocolitis (NEC) in preterm infants. Numerous studies in animal models indicate HM-derived small extracellular vesicles (HMEV) reduce severity of inflammation; however, data on human-specific models are limited. Isolated HMEV were characterized from early-HM (colostrum and transitional), mature-HM, and a combined, pasteurized donor bank-like HM sample (pool-); pool-HMEV retains a profile aligned with HMEV from both early- and mature-HM samples. Exposure to pool-HMEV initiates unique gene signatures associated with reduction of inflammation including NFkB-driven TNFα signaling in human intestinal enteroids (HIEs) established from neonates with intestinal atresia or NEC. Prior exposure of HIEs to pool-HMEV lowers the magnitude of EGTA- and TNF-induced barrier disruption. This foundational research demonstrates HMEVs cause transcriptional and functional changes to the human intestinal epithelium and will support future studies on HMEV-based therapeutics.
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