AUTHOR=Di Dong-sheng , Li Can , Dai Yu , Wei Mu-hong , Wang Shan-shan , Song Wen-jing , Zhou Hao-long , Cui Yuan , Zhang Ru-yi , Huang Qin , Wang Qi 

TITLE=Integrative Analysis of LGR5/6 Gene Variants, Gut Microbiota Composition and Osteoporosis Risk in Elderly Population

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.765008

DOI=10.3389/fmicb.2021.765008

ISSN=1664-302X

ABSTRACT=<p><bold>Objective:</bold> This study aimed to explore the relationships between the common variants of R-spondin/Wnt signaling genes, gut microbiota composition, and osteoporosis (OP) risk in elderly Chinese Han population.</p><p><bold>Design:</bold> Dual-energy X-ray absorptiometry was used to obtain the OP-associated measurements at multiple skeleton sites among all 1,168 participants. Genotyping data was obtained by using the next-generation sequencing in the discovery stage (<italic>n</italic> = 400, 228 OP patients) and SNPscan technology in the replication stage (<italic>n</italic> = 768, 356 OP patients). Bioinformatic analysis was performed to provide more evidence for the genotype-OP associations. The 16S ribosomal RNA gene high-throughput sequencing technology was adopted to explore OP-associated gut microbiota variations.</p><p><bold>Results:</bold> The genetic variants of rs10920362 in the <italic>LGR6</italic> gene (<italic>P</italic>-FDR = 1.19 × 10<sup>–6</sup>) and rs11178860 in the <italic>LGR5</italic> gene (<italic>P</italic>-FDR = 1.51 × 10<sup>–4</sup>) were found to associate with OP risk significantly. Several microbial taxa were associated with the BMDs and T-scores at multiple skeleton sites. The associations between rs10920362 and BMD-associated microbiota maintained significance after adjusting confounders. The rs10920362 CT/TT genotype associated with a decreased relative abundance of <italic>Actinobacteria</italic> (β = −1.32, <italic>P</italic> &lt; 0.001), <italic>Bifidobacteriaceae</italic> (β = −1.70, <italic>P</italic> &lt; 0.001), and <italic>Bifidobacterium</italic> (β = −1.70, <italic>P</italic> &lt; 0.001) compared to the CC genotype.</p><p><bold>Conclusion:</bold> Our findings suggested that the variants loci of <italic>LGR6</italic> may be associate with OP pathogenesis via gut microbiota modifications. The relationship between host genetics and gut microbiome provides new perspectives about OP prevention and treatment.</p>