Dataset Information

Lactobacillus rhamnosus GG attenuates tenofovir disoproxil fumarate-induced bone loss in male mice via gut-microbiota-dependent anti-inflammation.

ABSTRACT: Background:Although antiretroviral agents trigger bone loss in human immunodeficiency virus patients, tenofovir disoproxil fumarate (TDF) induces more severe bone damage, such as osteoporosis. While, the mechanisms are unclear, probiotic supplements may be effective against osteoporosis. Methods:C57BL6/J mice were administered with Lactobacillus rhamnosus GG (LGG)+TDF, TDF, and zoledronic acid+TDF, respectively. Bone morphometry and biomechanics were evaluated using microcomputed tomography, bone slicing, and flexural tests. The lymphocyte, proinflammatory cytokines, and intestinal permeability levels were detected using enzyme-linked immunosorbent assays, quantitative real-time polymerase chain reaction, and flow cytometry. The gut microbiota composition and metabolomics were analyzed using 16S recombinant deoxyribonucleic acid pyrosequencing and ultra-performance liquid-chromatography-quadrupole time-of-flight mass spectrometry. Results:LGG administered orally induced marked increases in trabecular bone microarchitecture, cortical bone volume, and biomechanical properties in the LGG+TDF group compared with that in the TDF-only group. Moreover, LGG treatment increased intestinal barrier integrity, expanded regulatory T cells, decreased Th17 cells, and downregulated osteoclastogenesis-related cytokines in the bone marrow, spleen, and gut. Furthermore, LGG reconstructed the gut microbiota and changed the metabolite composition, especially lysophosphatidylcholine levels. However, the amount of N-acetyl-leukotriene E4 was the highest in the TDF-only group. Conclusion:LGG reconstructed the community structure of the gut microbiota, promoted the expression of lysophosphatidylcholines, and improved intestinal integrity to suppress the TDF-induced inflammatory response, which resulted in attenuation of TDF-induced bone loss in mice. LGG probiotics may be a safe and effective strategy to prevent and treat TDF-induced osteoporosis.

SUBMITTER: Liu H

PROVIDER: S-EPMC6610433 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

<i>Lactobacillus rhamnosus</i> GG attenuates tenofovir disoproxil fumarate-induced bone loss in male mice <i>via</i> gut-microbiota-dependent anti-inflammation.

Liu Hao H Gu Ranli R Li Wei W Zhou Wen W Cong Zhe Z Xue Jing J Liu Yunsong Y Wei Qiang Q Zhou Yongsheng Y

Therapeutic advances in chronic disease 20190703

<h4>Background</h4>Although antiretroviral agents trigger bone loss in human immunodeficiency virus patients, tenofovir disoproxil fumarate (TDF) induces more severe bone damage, such as osteoporosis. While, the mechanisms are unclear, probiotic supplements may be effective against osteoporosis.<h4>Methods</h4>C57BL6/J mice were administered with <i>Lactobacillus rhamnosus</i> GG (LGG)+TDF, TDF, and zoledronic acid+TDF, respectively. Bone morphometry and biomechanics were evaluated using microco ...[more]

PMID: 31321013

Similar Datasets

Project description:BackgroundIn human immunodeficiency virus (HIV) treatment, tenofovir alafenamide (TAF) is associated with greater increases in all fasting cholesterol subgroups compared with tenofovir disoproxil fumarate (TDF). Because lipid abnormalities may contribute to cardiovascular morbidity and mortality, cardiovascular risk assessment is integral to routine HIV care. This post hoc study evaluates the impact of lipid changes on predicted atherosclerotic cardiovascular disease (ASCVD) risk and statin eligibility in treatment-naive adults living with HIV treated with TAF or TDF.MethodsParticipants (N = 1744) were randomized (1:1) to initiate TAF or TDF, each coformulated with elvitegravir/cobicistat/emtricitabine (studies GS-US-292-0104 and GS-US-292-0111). Eligibility for statin therapy and estimated 10-year ASCVD risk among adults aged 40-79 years treated with TAF or TDF for 96 weeks (W96) were analyzed based on American College of Cardiology/American Heart Association Pooled Cohort Equations. Categorical shifts in 10-year ASCVD risk from <7.5% to ≥7.5% by W96 on TAF versus TDF were calculated.ResultsParticipants initiating TAF versus TDF in the overall study population showed small but significant increases in median fasting lipid parameters at W96, including total cholesterol (191 vs 177 mg/dL; P < .001), low-density lipoprotein ([LDL] 119 vs 112 mg/dL; P < .001), and high-density lipoprotein ([HDL] 51 vs 48 mg/dL; P < .001), respectively. At baseline, 18% and 23% on TAF versus TDF had a 10-year ASCVD risk score ≥7.5%, with mean risk scores low overall for TAF versus TDF at baseline (4.9% vs 5.4%; P = .35) and W96 (6.1% vs 6.2%; P = .04). Increases in ASCVD risk from baseline to W96 were driven by both increasing age and changes in total cholesterol (TC) and HDL cholesterol. At W96, TC/HDL ratios (median) were 3.7 for both groups (P = .69). There was no difference between shifts in categorical risk for TAF versus TDF (9% vs 5%; P = .19). Eligibility for high-intensity statin therapy were similar for TAF versus TDF groups (19% vs 21%; P = .47).ConclusionsLipid changes with TAF as part of coformulated regimens do not substantively affect CVD risk profiles compared with TDF.

Dataset Information

Lactobacillus rhamnosus GG attenuates tenofovir disoproxil fumarate-induced bone loss in male mice via gut-microbiota-dependent anti-inflammation.

Publications

<i>Lactobacillus rhamnosus</i> GG attenuates tenofovir disoproxil fumarate-induced bone loss in male mice <i>via</i> gut-microbiota-dependent anti-inflammation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets