Preterm human milk contains a large pool of latent TGF-[Beta], which can be activated by exogenous neuraminidase

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2013-06, Vol.304 (12), p.G1055
• Main Authors: Namachivayam, Kopperuncholan, Blanco, Cynthia L, Frost, Brandy L, Reeves, Aaron A, Jagadeeswaran, Ramasamy, MohanKumar, Krishnan, Safarulla, Azif, Mandal, Partha, Garzon, Steven A, Raj, J Usha, Maheshwari, Akhil
• Format: Article
• Language: English
• Subjects: Babies; Cells; Immunoassay; Inflammatory bowel disease; Milk; Premature birth; Tissues
• ISSN: 0193-1857; 1522-1547

Human milk contains substantial amounts of transforming growth factor (TGF)-β, particularly the isoform TGF-β2. We previously showed in preclinical models that enterally administered TGF-β2 can protect against necrotizing enterocolitis (NEC), an inflammatory bowel necrosis of premature infants. In this study we hypothesized that premature infants remain at higher risk of NEC than full-term infants, even when they receive their own mother's milk, because preterm human milk contains less bioactive TGF-β than full-term milk. Our objective was to compare TGF-β bioactivity in preterm vs. full-term milk and identify factors that activate milk-borne TGF-β. Mothers who delivered between 23 0/7 and 31 6/7 wk or at ≥37 wk of gestation provided milk samples at serial time points. TGF-β bioactivity and NF-kB signaling were measured using specific reporter cells and in murine intestinal tissue explants. TGF-β1, TGF-β2, TGF-β3, and various TGF-β activators were measured by real-time PCR, enzyme immunoassays, or established enzymatic activity assays. Preterm human milk showed minimal TGF-β bioactivity in the native state but contained a large pool of latent TGF-β. TGF-β2 was the predominant isoform of TGF-β in preterm milk. Using a combination of several in vitro and ex vivo models, we show that neuraminidase is a key regulator of TGF-β bioactivity in human milk. Finally, we show that addition of bacterial neuraminidase to preterm human milk increased TGF-β bioactivity. Preterm milk contains large quantities of TGF-β, but most of it is in an inactive state. Addition of neuraminidase can increase TGF-β bioactivity in preterm milk and enhance its anti-inflammatory effects. [PUBLICATION ABSTRACT]