Feeding a diet devoid of choline to lactating rodents restricts growth and lymphocyte development in offspring

Abstract

The nutrient choline is necessary for membrane synthesis and methyl donation, with increased requirements during lactation. The majority of immune development occurs postnatally, but the importance of choline supply for immune development during this critical period is unknown. The objective of this study was to determine the importance of maternal supply of choline during suckling on immune function in their offspring among rodents. At parturition, Sprague-Dawley dams were randomised to either a choline-devoid (ChD; n 7) or cholinesufficient (ChS, 1 g/kg choline; n 10) diet with their offspring euthanised at 3 weeks of age. In a second experiment, offspring were weaned to a ChS diet until 10 weeks of age (ChD-ChS, n 5 and ChS-ChS, n 9). Splenocytes were isolated, and parameters of immune function were measured. The ChD offspring received less choline in breast milk and had lower final body and organ weight compared with ChS offspring (P < 0·05), but this effect disappeared by week 10 with choline supplementation from weaning. ChD offspring had a higher proportion of T cells expressing activation markers (CD71 or CD28) and a lower proportion of total B cells (CD45RA+) and responded less to T cell stimulation (lower stimulation index and less IFN-γ production) ex vivo (P < 0·05). ChD-ChS offspring had a lower proportion of total and activated CD4+ T cells, and produced less IL-6 after mitogen stimulation compared with cells from ChS-ChS (P < 0·05). Our study suggests that choline is required in the suckling diet to facilitate immune development, and choline deprivation during this critical period has lasting effects on T cell function later in life.

Comparing docosahexaenoic acid (DHA) concomitant with neoadjuvant chemotherapy versus neoadjuvant chemotherapy alone in the treatment of breast cancer (DHA WIN): protocol of a double-blind, phase II, randomised controlled trial

“…IL-1 β, IL-2, IL-6, IL-10, TNFα and interferon-γ (pg/mL) cytokines will be measured using electrochemiluminescent multiplex assays (Meso Scale Discovery) or by individual ELISA assays. Cytokines listed above and inflammatory markers including CRP in plasma will be measured by electrochemiluminescent multiplex assays (Meso Scale Discovery) as previously described 49. Cytokines and inflammatory markers in plasma and cytokines from cultured lymphocytes will be analysed when all samples have been collected.…”

Feeding a Mixture of Choline Forms to Lactating Dams Improves the Development of the Immune System in Sprague-Dawley Rat Offspring

“…Based on previous studies using a similar model [8,13], it is estimated that five to six rats per diet group are required to assess significant changes in immune function (i.e., ex vivo cytokine production as the primary outcome). Data were analyzed using a one-way ANOVA in SAS (v9.4, Cary, NC, USA) with diet as the main effect.…”

“…Substantial development also occurs during the suckling/lactation period for the brain [4], intestine/liver [5], and the immune system [6]. Using the Sprague-Dawley rat as a healthy rodent model, we have demonstrated that choline is required in the maternal diet during lactation for optimal immune function in the mother [7] as well as for the development of the immune system in their offspring [8]. This confirmed that an exogenous supply of choline during lactation is essential for infant and maternal immune function.…”

Feeding a Mixture of Choline Forms during Lactation Improves Offspring Growth and Maternal Lymphocyte Response to Ex Vivo Immune Challenges

“…Choline is an essential micronutrient required in the maternal diet during lactation to ensure adequate choline concentrations in breast milk, support offspring growth [ 1 , 2 ] and maintain maternal immune function [ 1 ] and intestinal health [ 3 ]. To enable breast milk to meet the demand by the infant to support developing tissues, maternal dietary choline requirements increase, from 425 mg/day for non-pregnant, non-lactating women to 550 mg/day for lactating women.…”

“…Despite the increased demands during lactation, epidemiological data suggests that many women during this key developmental period are not meeting daily recommendations [ 4 ]. We have previously demonstrated that an exogenous source of choline is essential in the maternal diet during lactation for optimal immune function of the mother [ 1 ] and the development of the immune system in their offspring [ 2 ]. In human populations [ 5 , 6 ], including women during lactation [ 4 ], dietary choline is consumed as a variety of forms, primarily as lipid-soluble phosphatidylcholine (PC) (46%), and water-soluble free choline (23%) and glycerophosphocholine (GPC) (19%).…”