Dataset Information

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

ABSTRACT: Objective: 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. Design: 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 (n = 400, 228 OP patients) and SNPscan technology in the replication stage (n = 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. Results: The genetic variants of rs10920362 in the LGR6 gene (P-FDR = 1.19 × 10^-6) and rs11178860 in the LGR5 gene (P-FDR = 1.51 × 10^-4) 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 Actinobacteria (β = -1.32, P < 0.001), Bifidobacteriaceae (β = -1.70, P < 0.001), and Bifidobacterium (β = -1.70, P < 0.001) compared to the CC genotype. Conclusion: Our findings suggested that the variants loci of LGR6 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.

SUBMITTER: Di DS

PROVIDER: S-EPMC8593465 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Di Dong-Sheng DS Li Can C Dai Yu Y Wei Mu-Hong MH Wang Shan-Shan SS Song Wen-Jing WJ Zhou Hao-Long HL Cui Yuan Y Zhang Ru-Yi RY Huang Qin Q Wang Qi Q

Frontiers in microbiology 20211102

Objective: 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. Design: 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 (n = 400, 228 OP patients) and ...[more]

PMID: 34795657

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Project description:ObjectiveAccumulative evidence suggests that gut microbiota play an important role in bone remodeling and hence bone health maintenance. This study aimed to explore the association of gut microbiota with the risk of osteoporosis and to identify potential disease-related taxa, which may be promising targets in osteoporosis prevention and treatment in the future.MethodsAbsolute quantification 16S ribosomal RNA gene sequencing was used to detect absolute and relative abundances of gut microbiota in 44 patients with osteoporosis and 64 controls. In combination with one of our previous studies, a total of 175 samples were involved in the relative abundance analysis.ResultsCompared with the controls, the patients with osteoporosis had higher absolute and relative abundances of Bacteroidetes phylum, and Bacteroides and Eisenbergiella genera. The absolute abundances of Clostridium_XlVa, Coprococcus, Lactobacillus, and Eggerthella genera increased, and that of the Veillonella genus decreased in the osteoporosis group. As for relative abundance, that of the Parabacteroides and Flavonifractor genera increased, whereas that of the Raoultella genus decreased in the osteoporosis group. Controlling for potential confounders, the associations of Clostridium_XlVa, Coprococcus, and Veillonella genera with the risk of osteoporosis did not maintain significance. Ridge regression analysis suggested that Bacteroides is associated with reduced bone mineral density (BMD) and T-score at lumbar spines, and Anaerovorax is associated with increased BMD at the femoral neck. Functional predictions revealed that 10 Kyoto Encyclopedia of Genes and Genomes pathways were enriched in the osteoporosis group.ConclusionsGut microbiota compositions may contribute to the risk of osteoporosis. Several specific taxa and functional pathways are identified to associate with reduced bone density, thus providing epidemiologic evidence for the potential role of aberrant gut microbiota in osteoporosis pathogenesis.

Project description:BackgroundPostmenopausal osteoporosis (PMO) is influenced by estrogen metabolism and immune response, which are modulated by several factors including the microbiome and inflammation. Therefore, there is increasing interest in understanding the role of microbiota in PMO.ObjectivesTo investigate variations in gut microbiota (GM) and vaginal microbiota (VM) in postmenopausal women with osteoporosis.MethodsA total of 132 postmenopausal women were recruited for the study and divided into osteoporosis (n = 34), osteopenia (n = 47), and control (n = 51) groups based on their T score. The serum levels of interleukin (IL)-10, tumor necrosis factor (TNF)-α, and lipopolysaccharide-binding protein were determined via enzyme-linked immunosorbent assay. Additionally, 16S rRNA gene V3-V4 region sequencing was performed to investigate the GM and VM of the participants.ResultsSignificant differences were observed in the microbial compositions of fecal and vaginal samples between groups (p < 0.05). It was noted that for GM, Romboutsia, unclassified_Mollicutes, and Weissella spp. were enriched in the control group, whereas the abundances of Fusicatenibacter, Lachnoclostridium, and Megamonas spp. were higher in the osteoporosis group than in the other groups. Additionally, for VM, Lactobacillus was enriched in the control group, whereas the abundances of Peptoniphilus, Propionimicrobium, and Gallicola spp. were higher in the osteoporosis group than in the other groups. The predicted functional capacities of GM and VM were different in the various groups. We also found that the serum level of IL-10 in the osteoporosis group was significantly lower than that in the control group and osteopenia group, while TNF-α was significantly higher in the osteoporosis group than that in the control group (p < 0.05).ConclusionThe results show that changes in BMD in postmenopausal women are associated with the changes in GM and VM; however, changes in GM are more closely correlated with PMO than VM.

Project description:The gut microbiota has been implicated in immunoglobin A nephropathy (IgAN) because the intestinal immune response is assumed to be one of the disease triggers. Since the microbial composition is heritable, we hypothesize that genetic variants controlling gut microbiota composition may be associated with susceptibility to IgAN or clinical phenotypes. A total of 175 gut-microbiome-associated genetic variants were retrieved from the Genome-Wide Association Study (GWAS) Catalog. Genetic associations were examined in 1,511 patients with IgAN and 4,469 controls. Subphenotype associations and microbiome annotations were undertaken for a better understanding of how genes shaped phenotypes. Likely candidate microbes suggested in genetic associations were validated using 16S rRNA gene sequencing in two independent data sets with 119 patients with IgAN and 45 controls in total. Nine genetic variants were associated with susceptibility to IgAN. Risk genotypes of LYZL1 were associated with higher serum levels of galactose-deficient IgA1 (Gd-IgA1). Other significant findings included the associations between the risk genotype of SIPA1L3 and early age at onset, PLTP and worse kidney function, and AL365503.1 and more severe hematuria. Besides, risk genotypes of LYZL1 and SIPA1L3 were associated with decreased abundances of Dialister and Bacilli, respectively. Risk genotypes of PLTP and AL365503.1 were associated with increased abundances of Erysipelotrichaceae and Lachnobacterium, respectively. 16S data validated a decreased tendency for Dialister and an increased tendency for Erysipelotrichaceae in IgAN. In this pilot study, our results provided preliminary evidence that the gut microbiota in IgAN was affected by host genetics and shed new light on candidate bacteria for future pathogenesis studies.IMPORTANCE The gut microbiota and host genetics are implicated in the pathogenesis of IgAN. Recent studies have confirmed that microbial compositions are heritable (microbiome quantitative trait loci [QTL]). The relationship between host genetics and the microbiota and the role of the microbiota in IgAN are unclear. We retrieved the GWAS Catalog and associated microbiome QTL in IgAN, observing that nine genetic variants were associated with IgAN susceptibility and some clinical phenotypes. In a consistent way, the decreased abundance of Dialister was associated with higher serum levels of Gd-IgA1, and 16S rRNA gene analysis confirmed the decreased abundance of Dialister in IgAN. These data provided preliminary evidence that the gut microbiota in IgAN was affected by host genetics, which is a new strategy for future pathogenesis and intervention studies.

Dataset Information

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

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Integrative Analysis of <i>LGR5/6</i> Gene Variants, Gut Microbiota Composition and Osteoporosis Risk in Elderly Population.

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