Human breast milk feeding induces stronger humoral immune response than formula feeding in neonatal porcine model

Abstract

Several studies indicate stronger humoral immune responses in breast‐fed than formula‐fed infants. The key to the beneficial impact of breastmilk on the gastrointestinal (GI) tract and immune system development is the interaction between diet and the gut microbiome. A more comprehensive, mechanistic understanding of this interaction has been hampered by challenges of studying this dynamic relationship in vivo in neonates and infants. We have developed a unique human breast milk‐fed piglet model to address this issue. This approach reduces limitations associated with sow‐feeding (e.g., exposure to sow nipple epidermis, fecal material, etc.) and obviates challenges that arise with the collection and compositional assessment of sow's milk. Piglets born at a breeding farm were sow‐fed for 48 hours, then moved to an AAALAC‐approved animal facility, and fed equicaloric diets either with human breast‐milk (HBM) or a dairy‐based infant formula (F) through age 21 days. Sow‐fed piglets were housed at the farm until age 20 days and all diet groups were weaned to a common ad libitum solid diet until day 51. Piglets were immunologically challenged with oral choleratoxin and intramuscular DTaP antigens on days 21 and 35. Immune response was evaluated on day 48 by measuring IgG to tetanus antigen, and IgA to choleratoxin antigen. Relative to non‐immunized piglets, in all diet groups' immunized piglets had expected antigen specific immune responses. However, relative to F‐fed piglets, HBM‐fed piglets showed higher tetanus‐specific IgG response in serum (log 4.4 vs 4.9, p<0.01), significantly more peripheral blood mononuclear cells (PBMCs) produced greater levels of IgG (p<0.05). Furthermore, on day 51 choleratoxin‐specific IgA producing cells were significantly higher in Peyer's patch (p<0.05) and mesenteric lymph nodes (MLN, p<0.05) in HBM‐fed piglets than F‐fed piglets. These effects were associated with a greater IgA response in serum (log 3.7 vs 4.4, p<0.05). Relative to F‐fed piglets, HBM‐fed showed significantly more NK (26% vs 13%), B (36% vs 10%) and Treg cell (11% vs 3.5%) populations in the mesenteric lymph nodes. In the Peyer's patch of F‐fed piglets significantly more gdT (11% vs 1%) and CD8 T (25% vs 15%) cells were observed. It is important to note that no major significant group differences were observed in the weight gain or general health throughout the feeding period. These data suggest that neonatal immune system development is influenced by specific factors in breast milk and further confirm findings from infant studies that breast milk feeding results in stronger mucosal and systemic immune responses. Furthermore, the sow‐fed group responses were similar to HBM‐fed piglets in most of the measurements suggesting that piglets fed with human breast‐milk may model breast‐fed infants. Mechanistic studies are underway to determine the role of microbiota in gut development and immune responses. This determination would be a major step toward translation between animal models and the human condition addressing challenges associated with procurement of GI tract samples under controlled conditions in infants.Support or Funding InformationFunding: USDA‐ARS Project 6026‐5100‐010‐05S