To investigate whether healthy term infants, fed an infant formula containing hydrolyzed whey protein (HWP-F, hydrolyzed whey/intact casein =63/37), differ in growth, gastrointestinal tolerance and stool characteristics from those fed an infant formula containing intact whey protein (IWP-F, intact whey/intact casein =61/39) or breast milk. Healthy term infants, born within 14 days of the study’s commencement, were randomly assigned to be fed IWP-F or HWP-F until 13 weeks of age, and breast-fed (BF) infants were enrolled as a reference group. Anthropometric measurements, gastrointestinal tolerance indexes and stool characteristics were assessed at baseline, and 7 and 13 weeks of age. There were no significant differences in any growth measurements and the occurrence of crying, spit-up and difficult defecation among the three feeding groups during the study period. However, daily feeding frequency was consistently lower in the formula-fed infants than in the BF group throughout the study (p < 0.05), and infants in the HWP-F group consumed more formula than those in the IWP-F group at 7 and 13 weeks of age (p ≤ 0.002). The HWP-F-fed infants had more similar stool characteristics to the breast-fed infants than infants in the IWP-F group at 13 weeks of age, regardless of frequency, volume, color or consistency of stool. This study demonstrates that the HWP-F could support the normal growth of healthy term infants, to a comparable extent to that of breast-fed infants during the first three months of life. Moreover, stool characteristics of HWP-F-fed infants are much closer to breast-fed infants than IWP-F-fed infants, but no significant gastrointestinal tolerance improvement was observed in HWP-F group.

Several small studies suggested gut microbiome might influence osteoporosis, but rare metabolomics evidence from human study had explained the link. This study examined the association of gut microbiome dysbiosis with osteoporosis and explored the potential pathways by using fecal and serum metabolomics. We analyzed gut microbiota compositions by 16S rRNA profiling and bone density (BMD) using a dual-energy X-ray absorptiometry in 1776 community-based adults. Targeted metabolomics in feces (15 categories) and serum (12 categories) were further analyzed in 971 participants with ultra-performance liquid chromatography coupled to tandem mass spectrometry. This study showed osteoporosis was related to gut microbiota beta diversity, taxonomy and functional composition. The relative abundance of Actinobacillus, Blautia, Oscillospira, Bacteroides and Phascolarctobacterium was positively, while Veillonellaceae other, Collinsella and Ruminococcaceae other were inversely, associated with the presence of osteoporosis, which related to higher levels of peptidases and transcription machinery in microbial function. Fecal and serum metabolomics analyses suggested that the tyrosine metabolism and the tryptophan metabolism in feces and the valine, leucine and isoleucine degradation in serum were significantly linked to the identified microbiota biomarkers and osteoporosis. This large population-based study provided the robust evidence connecting gut dysbiosis, fecal and serum metabolomics with osteoporosis. Our results suggested that gut dysbiosis and amino acid metabolism could be potential targets for the intervention of osteoporosis.