Offspring immune development is dependent on the amount and form of choline in the maternal diet during suckling
Authors: Lewis Erin D. , Richard Caroline , Goruk Susan , Dellschaft Neele , Curtis Jonathan M. , Jacobs René L. , Field Catherine J. 
Published: November 2023

Exogenous choline needs increase in the postnatal period to meet infant development demands. There is limited knowledge on choline intake during lactation or the role of different choline forms. We developed a database for the choline content of foods and estimated intake in the Alberta Pregnancy Outcomes and Nutrition cohort. During lactation, 90% of women (n=1000) consumed below the DRI, with phosphatidylcholine (PC) and free choline comprising ~65% of total choline. In the early postnatal period, the immune system undergoes rapid development and requires a choline supply. The importance of the contribution of dietary choline to immune development during this period has not been explored. In a rodent model, the study objectives were to determine the effect of 1) dietary choline deficiency and 2) the 2 major forms of dietary choline (PC vs. free choline), on parameters of immune development and function in suckled offspring. At parturition, dams were randomized to either: 0 g/kg choline (D; n=7), 1.0 g/kg choline as free choline (C; n=15) or 1.0 g/kg choline as PC (PC; n=5). Diets were nutritionally complete, isocaloric, with similar fatty acid composition. At 3 wks, spleen immune cell phenotypes (by 4‐colour flow cytometry) and ex vivo cytokine production (by ELISA) after Concanavalin A (ConA), lipopolysaccharide (LPS) or CD3/CD28 (T cell antigen) stimulation was measured. Stomach content (representing breast milk), plasma and spleen choline content was measured by liquid chromatography‐mass spectrometry (LC‐MS). D pups had lower body and organ weight, splenocyte number and total choline in stomach compared to C pups (P<0.05). D pups had a higher proportion of helper T cells expressing activation (CD71) and co‐stimulation (CD28) markers and lower proportion of total B cells (CD45RA+) compared to C pups. D pups produced less IFN‐γ (CD3/CD28 stimulation) and less IL‐1β (LPS stimulation). Compared to C pups, splenocytes from PC pups had a lower proportion of antigen presenting cells (OX12+, OX6+, CD68+/CD11b/c+ cells) but produced more IL‐2, IFN‐g and IL‐6 (ConA stimulation), and more IL‐6 and TNF‐α (LPS stimulation). Choline form (fed at 1g/kg) did not alter growth, splenocyte number or total choline in stomach. However, PC pups had a higher proportion of choline as lysoPC and lower proportion as free choline (P<0.05). PC pups had a higher concentration of PC in plasma and splenocyte phospholipids compared to C pups, later confirmed in an in vitro study that may explain the functional differences between choline forms. Our studies suggest choline is essential in the maternal diet during suckling for offspring immune development and providing choline as PC, compared to free choline, promoted maturation and improved immune function. Together with our findings of possible suboptimal intake in lactating women, future research should focus on identifying potential benefits of increasing both total and PC sources of choline in the maternal diet to support immune development in the infant.

Support or Funding Information

Supported by NSERC, Alberta Livestock and Meat Agency and Alberta Innovates Biosolutions. EDL holds an Izaak Walton Killam Memorial and NSERC Postgraduate Doctoral Scholarships