Why aren't the antibodies in the mother's milk digested by the infant's digestive system?

Question

Why aren't the antibodies in the mother's milk digested by the infant's digestive system?

Enzymes like pepsin have been found to be present in infant's digestive system(1). Though the pH in the stomach of infants is high(The gastric pH of neonates between 2 and 13 days increases from 3.5 to 5-7 for 2 h after ingestion of human milk)(2) activity of pepsin like enzymes from mother's milk itself or infant's stomach is appreciable(1). Moreover tryspin function in infant's intestine is equal to the level in adults by the age of one month(3). Many more proteases are also seen in both mother's milk and in infant's digestive system(1). If this is the case why are antibodies present in mothers milk not digested by the infant?

I have two hypotheses regarding this

1. Glycoproteins by their nature cannot be digested by the enzymes in infant.
2. Antibodies are present in such large amounts that many of them are undigested by chance.

I have no idea whether either of these are true. Any ideas will be appreciated.

References:

(1)Thérèse A. Holton et al. Following the Digestion of Milk Proteins from Mother to Baby.Journal of Proteome Research 2014, 13 (12), 5777-5783

(2)Mason, S. Some aspects of gastric function in the newborn Arch. Dis. Child. 1962, 37 (194), 387-390

(3)Lebenthal E, Lee PC. Development of functional responses in human exocrine pancreas. Pediatrics. 1980, 66(4), 556-560

Answer 1

Demers-Mathieu et al. ¹ used ELISA to quantify immunoglobulin concentrations from milk after 2 hours of digestion in the stomachs of preterm-delivered and term-delivered infants. From the abstract:

Total IgA concentration decreased by 60% from human milk to the preterm infant stomach and decreased by 48% in the term infant stomach. Total IgM and IgG concentrations decreased by 33% and 77%, respectively, from human milk to the term infant stomach but were stable in the preterm infant stomach.

The authors note that the infants enrolled in this study had a variety of medical conditions, but "no overt gastrointestinal tract issues or other medical conditions that have been associated with an effect on gastric emptying or digestion capacity." Two hours of digestion was chosen to ensure recovery of sample from the stomach while maximizing digestion time, per the gastric emptying times observed in Siegel et al. ²

So, it appears that term infants are digesting antibodies from their mothers, but a substantial portion of immunoglobulins remain intact. Weaver et al. ³ report IgA concentrations between 0.311 and 1.247 g/L across 1600 breast milk samples, with negative correlations to maternal age and parity.

Taking the median IgA concentration of 0.708 g/L, a 48% reduction gives 0.368 g/L post-digestion. Dewey et al. ⁴ report that 3 month-old infants consume 818 mL of breast milk (assuming 1 g/mL) per day, on average, which suggests that ~300 mg IgA are available to the infant intestine from daily breast milk consumption. If the adult human gut produces 40 to 60 mg IgA per kg body weight per day ⁵, then ~300 mg IgA is in the ballpark of what a 6 kg infant would need to phenocopy the IgA concentration of an adult gut, assuming limited immunoglobulin production by infants themselves.

So, it seems like hypothesis #2 is close to the truth, at least for highly abundant antibodies like immunoglobulins:

Antibodies are present in such large amounts that many of them are undigested by chance.

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1. Demers-Mathieu V, Underwood MA, Beverly RL, Nielsen SD, Dallas DC. Comparison of Human Milk Immunoglobulin Survival during Gastric Digestion between Preterm and Term Infants. Nutrients. 2018 May 17;10(5):631.
2. Siegel M, Lebenthal E, Topper W, Krantz B, Li PK. Gastric emptying in prematures of isocaloric feedings with differing osmolalities. Pediatr Res. 1982;16(2):141-147.
3. Weaver LT, Arthur HM, Bunn JE, Thomas JE. Human milk IgA concentrations during the first year of lactation. Arch Dis Child. 1998 Mar;78(3):235-9.
4. Dewey KG, Heinig MJ, Nommsen LA, Lonnerdal B. Maternal versus infant factors related to breast milk intake and residual milk volume: the DARLING study. Pediatrics. 1991;87(6):829-837.
5. Jacob Campbell, James Berry, Yu Liang. Chapter 71 - Anatomy and Physiology of the Small Intestine, Editor: Charles J. Yeo, Shackelford's Surgery of the Alimentary Tract (Eighth Edition). [via ScienceDirect]