Human milk nutrient fortifiers alter the developing gastrointestinal microbiota of very-low-birth-weight infants.

Nutrient fortifiers are added to human milk to support the development of very-low-birth-weight infants. Currently, bovine-milk-based fortifiers (BMBFs) are predominantly administered, with increasing interest in adopting human-milk-based fortifiers (HMBFs). Although beneficial for growth, their effects on the gastrointestinal microbiota are unclear. This triple-blind, randomized clinical trial (NCT02137473) tested how nutrient-enriching human milk with HMBF versus BMBF affects the gastrointestinal microbiota of infants born < 1,250 g during hospitalization. HMBF-fed infants (n = 63, n = 269 stools) showed lower microbial diversity, altered microbial community structure, and changes in predicted microbial functions compared with BMBF-fed infants (n = 56, n = 239 stools). HMBF-fed infants had higher relative and normalized abundances of unclassified Enterobacteriaceae and lower abundances of Clostridium sensu stricto. Post hoc analyses identified dose-dependent relationships between individual feed components (volumes of mother's milk, donor milk, and fortifiers) and the microbiota. These results highlight how nutrient fortifiers impact the microbiota of very-low-birth-weight infants during a critical developmental window.

High Intakes of [6S]-5-Methyltetrahydrofolic Acid Compared with Folic Acid during Pregnancy Programs Central and Peripheral Mechanisms Favouring Increased Food Intake and Body Weight of Mature Female Offspring.

Supplementation with [6S]-5-methyltetrahydrofolic acid (MTHF) is recommended as an alternative to folic acid (FA) in prenatal supplements. This study compared equimolar gestational FA and MTHF diets on energy regulation of female offspring. Wistar rats were fed an AIN-93G diet with recommended (2 mg/kg diet) or 5-fold (5X) intakes of MTHF or FA. At weaning, female offspring were fed a 45% fat diet until 19 weeks. The 5X-MTHF offspring had higher body weight (>15%), food intake (8%), light-cycle energy expenditure, and lower activity compared to 5X-FA offspring (p < 0.05). Both the 5X offspring had higher plasma levels of the anorectic hormone leptin at birth (60%) and at 19 weeks (40%), and lower liver weight and total liver lipids compared to the 1X offspring (p < 0.05). Hypothalamic mRNA expression of leptin receptor (ObRb) was lower, and of suppressor of cytokine signaling-3 (Socs3) was higher in the 5X-MTHF offspring (p < 0.05), suggesting central leptin dysregulation. In contrast, the 5X-FA offspring had higher expression of genes encoding for dopamine and GABA- neurotransmitter receptors (p < 0.01), consistent with their phenotype and reduced food intake. When fed folate diets at the requirement level, no differences were found due to form in the offspring. We conclude that MTHF compared to FA consumed at high levels in the gestational diets program central and peripheral mechanisms to favour increased weight gain in the offspring. These pre-clinical findings caution against high gestational intakes of folates of either form and encourage clinical trials examining their long-term health effects when consumed during pregnancy.