Human Breast Milk and Infant Formulas Differentially Modify the Intestinal Microbiota in Human Infants and Host Physiology in Rats

Abstract

Background: In the absence of human breast milk, infant and follow-on formulas can still promote efficient growth and development. However, infant formulas can differ in their nutritional value.

Objective: The objective of this study was to compare the effects of human milk (HM) and infant formulas in human infants and a weanling rat model.

Methods: In a 3 wk clinical randomized controlled trial, babies (7- to 90-d-old, male-to-female ratio 1:1) were exclusively breastfed (BF), exclusively fed Synlait Pure Canterbury Stage 1 infant formula (SPCF), or fed assorted standard formulas (SFs) purchased by their parents. We also compared feeding HM or SPCF in weanling male Sprague-Dawley rats for 28 d. We examined the effects of HM and infant formulas on fecal short chain fatty acids (SCFAs) and bacterial composition in human infants, and intestinal SCFAs, the microbiota, and host physiology in weanling rats.

Results: Fecal Bifidobacterium concentrations (mean log copy number ± SEM) were higher (P = 0.003) in BF (8.17 ± 0.3) and SPCF-fed infants (8.29 ± 0.3) compared with those fed the SFs (6.94 ± 0.3). Fecal acetic acid (mean ± SEM) was also higher (P = 0.007) in the BF (5.5 ± 0.2 mg/g) and SPCF (5.3 ± 2.4 mg/g) groups compared with SF-fed babies (4.3 ± 0.2 mg/g). Colonic SCFAs did not differ between HM- and SPCF-fed rats. However, cecal acetic acid concentrations were higher (P = 0.001) in rats fed HM (42.6 ± 2.6 mg/g) than in those fed SPCF (30.6 ± 0.8 mg/g). Cecal transcriptome, proteome, and plasma metabolite analyses indicated that the growth and maturation of intestinal tissue was more highly promoted by HM than SPCF.

Conclusions: Fecal bacterial composition and SCFA concentrations were similar in babies fed SPCF or HM. However, results from the rat study showed substantial differences in host physiology between rats fed HM and SPCF. This trial was registered at Shanghai Jiào tong University School of Medicine as XHEC-C-2012-024.

Keywords: breast milk; infant formula; metabolomics; microbiota; transcriptomics.