Osteoporosis and its associated fractures are highly prevalent in older women. Recent studies have shown that gut microbiota play important roles in regulating bone metabolism. A previous randomized controlled trial (RCT) found that supplementation with Lactobacillus reuteri ATCC PTA 6475 (L.reuteri) led to substantially reduced bone loss in older women with low BMD. However, the total metabolic effects of L. reuteri supplementation on older women are still not clear. In this study, a post hoc analysis (not predefined) of serum metabolomic profiles of older women from the previous RCT was performed to investigate the metabolic dynamics over 1 year and to evaluate the effects of L. reuteri supplementation on human metabolism. Distinct segregation of the L. reuteri and placebo groups in response to the treatment was revealed by partial least squares-discriminant analysis. Although no individual metabolite was differentially and significantly associated with treatment after correction for multiple testing, 97 metabolites responded differentially at any one time point between L. reuteri and placebo groups (variable importance in projection score >1 and p value <0.05). These metabolites were involved in multiple processes, including amino acid, peptide, and lipid metabolism. Butyrylcarnitine was particularly increased at all investigated time points in the L. reuteri group compared with placebo, indicating that the effects of L. reuteri on bone loss are mediated through butyrate signaling. Furthermore, the metabolomic profiles in a case (low BMD) and control population (high BMD) of elderly women were analyzed to confirm the associations between BMD and the identified metabolites regulated by L. reuteri supplementation. The amino acids, especially branched-chain amino acids, showed association with L. reuteri treatment and with low BMD in older women, and may serve as potential therapeutic targets.
Bibliographical noteFunding Information:
This study was funded by grants from the Novo Nordisk Foundation (NNF15OC0016798), the Knut and Alice Wallenberg Foundation, Vetenskapsr?det, and ALF/LUA grants from the Sahlgrenska University Hospital, Region V?stra G?taland. BioGaiaAB provided partial funding for the randomized controlled trial (see J Intern Med. 2018;284(3):307?317), which the current study is partially based upon. We would like to thank the late Associate Professor and MD Anna Nilsson for her dedicated work, for being an inspiration, and for her invaluable contributions to the planning of the study and data collection. We appreciate the valuable criticism and comments on the manuscript provided by Professor Fredrik B?ckhed. We would like to acknowledge Fredrik B?ckhed for useful discussions and comments. We also express our sincere gratitude to all the study participants in the included cohorts.
© 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
- BONE LOSS
- LACTOBACILLUS REUTERI