Targeting the gut-lung axis by synbiotic feeding to infants in a randomized controlled trial.

BACKGROUND: Formula-fed infants are at increased risk of infections. Due to the cross-talk between the mucosal systems of the gastrointestinal and respiratory tracts, adding synbiotics (prebiotics and probiotics) to infant formula may prevent infections even at distant sites. Infants that were born full term and weaned from breast milk were randomized to prebiotic formula (fructo- and galactooligosaccharides) or the same prebiotic formula with Lactobacillus paracasei ssp. paracasei F19 (synbiotics) from 1 to 6 months of age. The objective was to examine the synbiotic effects on gut microbiota development. RESULTS: Fecal samples collected at ages 1, 4, 6, and 12 months were analyzed using 16S rRNA gene sequencing and a combination of untargeted gas chromatography-mass spectrometry/liquid chromatography-mass spectrometry. These analyses revealed that the synbiotic group had a lower abundance of Klebsiella, a higher abundance of Bifidobacterium breve compared to the prebiotic group, and increases in the anti-microbial metabolite d-3-phenyllactic acid. We also analyzed the fecal metagenome and antibiotic resistome in the 11 infants that had been diagnosed with lower respiratory tract infection (cases) and 11 matched controls using deep metagenomic sequencing. Cases with lower respiratory tract infection had a higher abundance of Klebsiella species and antimicrobial resistance genes related to Klebsiella pneumoniae, compared to controls. The results obtained using 16S rRNA gene amplicon and metagenomic sequencing were confirmed in silico by successful recovery of the metagenome-assembled genomes of the bacteria of interest. CONCLUSIONS: This study demonstrates the additional benefit of feeding specific synbiotics to formula-fed infants over prebiotics only. Synbiotic feeding led to the underrepresentation of Klebsiella, enrichment of bifidobacteria, and increases in microbial degradation metabolites implicated in immune signaling and in the gut-lung and gut-skin axes. Our findings support future clinical evaluation of synbiotic formula in the prevention of infections and associated antibiotic treatment as a primary outcome when breastfeeding is not feasible. TRIAL REGISTRATION: ClinicalTrials.gov NCT01625273 . Retrospectively registered on 21 June 2012.

Effects of infant formula supplemented with prebiotics compared with synbiotics on growth up to the age of 12 mo: a randomized controlled trial.

BACKGROUND: Growth is an essential outcome measure for evaluating the safety of infant formulas (IF). We investigated the effects of consumption of IF supplemented with prebiotics (fructooligosaccharides, FOS, and galactooligosaccharides, GOS) compared with synbiotics (FOS/GOS and Lactobacillus paracasei ssp. paracasei strain F19) on the growth of healthy infants. METHODS: 182 full-term infants who were weaned completely from breast milk to IF at 28 d of age were randomly assigned to receive prebiotic- or synbiotic-supplemented, otherwise identical, IF until 6 mo of age (intervention period). RESULTS: A total of 146 (80%) infants were included in the intention-to-treat analysis at 6 mo. Anthropometric parameters were similar in the two groups during the intervention and follow-up period until 12 mo of age. Compared with the prebiotic group, a significant reduction in the cumulative incidence of lower respiratory tract infections was found in the synbiotic group; however, the confidence interval of the estimate was wide, resulting in uncertainty. CONCLUSION: The lack of a significant difference between the formula-fed groups in growth, or the occurrence of serious adverse events, supports the safety of using IF supplemented with synbiotics. Further studies are needed to evaluate the effects of such formula on lower-respiratory tract infections.

Total zinc absorption in young women, but not fractional zinc absorption, differs between vegetarian and meat-based diets with equal phytic acid content.

Zn bioavailability is often lower in vegetarian diets mainly due to low Zn and high phytic acid contents. The objective of the present study was to determine the fractional and total absorption of Zn from a vegetarian diet in comparison with meat diets with equal concentrations of phytic acid. A randomized cross-over design, comprising three whole-day diet periods of 5 d each, with a vegetarian diet or diets containing Polish-produced meat or Danish-produced meat, was conducted. Twelve healthy female subjects completed the study. All diets had a high content of phytic acid (1250 micromol/d) and in the meat diets the main meals contained 60 g pork meat. All main meals were extrinsically labelled with the radioactive isotope 65Zn and absorption of Zn was measured in a whole-body counter. The mean Zn content of the whole-day diet was: Polish meat diet 9.9 (SE 0.14) mg, Danish meat diet 9.4 (SE 0.19) mg and vegetarian diet 7.5 (SE 0.18) mg. No difference was observed in the fractional absorption of Zn (Polish meat diet: 27 (SE 1.2) %, Danish meat diet: 27 (SE 1.9) % and vegetarian diet: 23 (SE 2.6) %). A significantly lower amount of total Zn was absorbed from the vegetarian diet (mean Zn absorption of Polish meat diet: 2.7 (SE 0.12) mg/d (P<0.001), Danish meat diet: 2.6 (SE 0.17) mg/d (P=0.006) and vegetarian diet: 1.8 (SE 0.20) mg/d). In conclusion, the vegetarian diet compared with the meat-based diets resulted in lower amounts of absorbed Zn due to a higher content of Zn in the meat diets, but no difference was observed in the fractional absorption of Zn.

The importance of dietary composition for efficacy of iron absorption measured in a whole diet that includes rye bread fortified with ferrous fumerate: a radioisotope study in young women.

Fe absorption is affected by many dietary factors. The objective of the present study was to measure the effects of high v. low content of vitamin C, meat and phytic acid in whole diets with Fe-fortified bread on the efficacy of Fe absorption. Thirty-two healthy women with low Fe stores were randomised to three groups, each of which was given two of six test diets containing either low/high amounts of vitamin C, meat or phytic acid, respectively, in a cross-over design. Each diet was served throughout a 5 d period. Fe-fortified rye bread, extrinsically labelled with (59)Fe, was given with all main meals. Fe absorption was determined from whole-body counter measurements of (59)Fe retention. The fractional non-haem Fe absorption (corrected to a 40 % standard absorption by measurements from the reference dose) was 1.9 % v. 3.4 % (P=0.04) for the low/high vitamin C diets, 3.0 % v. 3.5 % (P=0.58) on the low/high meat diets and 4.9 % v. 3.8 % (P=0.24) on the low/high phytic acid diet, respectively. The total Fe absorbed (geometric mean with standard error) varied from 0.43 (se 0.11) mg from the diet with lowest bioavailability to 1.09 (se 0.18) mg from the diet with highest bioavailability (P<0.001). The present whole-diet study indicates that diet composition is a strong predictor of Fe absorption. In the diet with a low content of enhancers and a high content of inhibitors, vitamin C improved non-haem Fe absorption. The total Fe absorption varied 2.5-fold after small alterations of the content of enhancers and inhibitors in the diet.