The Association of Gut Microbiota With Osteoporosis Is Mediated by Amino Acid Metabolism: Multiomics in a Large Cohort

Abstract

Context Several small studies have suggested that the gut microbiome might influence osteoporosis, but there is little evidence from human metabolomics studies to explain this association. Objective This study examined the association of gut microbiome dysbiosis with osteoporosis and explored the potential pathways through which this association occurs using faecal and serum metabolomics. Methods We analysed the composition of the gut microbiota by 16S rRNA profiling and bone mineral density (BMD) using dual-energy X-ray absorptiometry in 1776 community-based adults. Targeted metabolomics in faeces (15 categories) and serum (12 categories) were further analysed in 971 participants using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Results This study showed that osteoporosis was related to the beta diversity, taxonomy and functional composition of the gut microbiota. The relative abundance of Actinobacillus, Blautia, Oscillospira, Bacteroides and Phascolarctobacterium was positively associated with osteoporosis. However, Veillonellaceae other, Collinsella and Ruminococcaceae other were inversely associated with the presence of osteoporosis. The association between microbiota biomarkers and osteoporosis was related to levels of peptidases and transcription machinery in microbial function. Faecal and serum metabolomics analyses suggested that tyrosine and tryptophan metabolism and valine, leucine and isoleucine degradation were significantly linked to the identified microbiota biomarkers and to osteoporosis, respectively. Conclusion This large population-based study provided robust evidence connecting gut dysbiosis, faecal metabolomics and serum metabolomics with osteoporosis. Our results suggest that gut dysbiosis and amino acid metabolism could be targets for intervention in osteoporosis.

Heat-Killed Lacticaseibacillus paracasei GMNL-653 Exerts Antiosteoporotic Effects by Restoring the Gut Microbiota Dysbiosis in Ovariectomized Mice

“…Hence, ion channels play critical roles in sustaining bone homeostasis. A cohort study reported that amino acid metabolism, such as tyrosine and tryptophan metabolism, was significantly related to gut dysbiosis and osteoporosis (68). Pyruvate also plays a pivotal role in various physiological processes as a counterion and could affect the absorption and availability of calcium through the epithelial cells (69).…”

Integrated Fecal Microbiome and Metabolomics Reveals a Novel Potential Biomarker for Predicting Tibial Dyschondroplasia in Chickens

“…In addition, gut-derived bacterial metabolites can penetrate through the gut into the bloodstream disrupting the bioenergetic machinery of host cells, which provides an essential pathway for the gut microbiota to regulate anatomically distant organs ( Lu et al, 2021 ; Tomasova et al, 2021 ). Therefore, the effect of changes in microbiome structure and composition on bone physiological functions has gradually attracted attention ( Chen et al, 2017 ; Castaneda et al, 2020 ; Hao et al, 2021 ; Ling et al, 2021 ).…”

“…The microbiome that resides in the gastrointestinal tract reflects physiological and metabolic properties. These microorganisms live symbiotically with the host to produce microbial metabolites, forming the host-microbe metabolic axis, which plays a vital role in animal nutritional metabolism and immune homeostasis, including the occurrence and development of disease ( Zaiss et al, 2019 ; Zheng et al, 2019 ; Kim et al, 2020 ; Wang et al, 2020 ; Ling et al, 2021 ; Murga-Garrido et al, 2021 ). More evidence has demonstrated that gut microbiota is a critical regulator in bone and that alterations in microbiota composition can contribute to pathological bone loss or reduced bone mineral density.…”

Association of serum 25-hydroxyvitamin D (25(OH)D) levels with the gut microbiota and metabolites in postmenopausal women in China

“…Phenylalanine is an essential amino acid that is the raw material for the synthesis of tyrosine. Fecal and serum metabolomics analyses suggested that tyrosine and tryptophan metabolism and valine, leucine, and isoleucine degradation were signi cantly linked to the identi ed microbiota biomarkers and osteoporosis, respectively [54]. Osteopenia is observed in some patients affected by phenylalanine hydroxylase-de cient phenylketonuria [55].…”