Gut Microbiota and Serum Metabolic Signatures of High-Fat-Induced Bone Loss in Mice

Abstract

BackgroundAccumulating evidence indicates that high-fat diet (HFD) is a controllable risk factor for osteoporosis, but the underlying mechanism remains to be elucidated. As a primary biological barrier for nutrient entry into the human body, the composition and function of gut microbiota (GM) can be altered rapidly by HFD, which may trigger abnormal bone metabolism. In the current study, we analyzed the signatures of GM and serum metabolomics in HFD-induced bone loss and explored the potential correlations of GM and serum metabolites on HFD-related bone loss.MethodsWe conducted a mouse model with HFD-induced bone loss through a 12-week diet intervention. Micro-CT, Osmium-μCT, and histological analyses were used to observe bone microstructure and bone marrow adipose tissue. Quantitative Real-Time PCR was applied to analyze gene expression related to osteogenesis, adipogenesis, and osteoclastogenesis. Enzyme-linked immunosorbent assay was used to measure the biochemical markers of bone turnover. 16s rDNA sequencing was employed to analyze the abundance of GM, and UHPLC-MS/MS was used to identify serum metabolites. Correlation analysis was performed to explore the relationships among bone phenotypes, GM, and the metabolome.ResultsHFD induced bone loss accompanied by bone marrow adipose tissue expansion and bone formation inhibition. In the HFD group, the relative abundance of Firmicutes was increased significantly, while Bacteroidetes, Actinobacteria, Epsilonbacteraeota, and Patescibacteria were decreased compared with the ND group. Association analysis showed that thirty-two bacterial genera were significantly related to bone volume per tissue volume (BV/TV). One hundred and forty-five serum metabolites were identified as differential metabolites associated with HFD intervention, which were significantly enriched in five pathways, such as purine metabolism, regulation of lipolysis in adipocyte and cGMP-PKG signaling pathway. Sixty-four diffiential metabolites were matched to the MS2 spectra; and ten of them were positively correlated with BV/TV and five were negatively correlated with BV/TV.ConclusionsThese findings indicated that the alternations of GM and serum metabolites were related to HFD-induced bone loss, which might provide new insights into explain the occurrence and development of HFD-related osteoporosis. The regulatory effects of GM and metabolites associated with HFD on bone homeostasis required further exploration.

The Effects of Tangning Ziyabitusi on Gut Microbiota and T lymphocyte Subsets in Impaired Glucose Regulation Rats

“…The relative abundance of Patescibacteria and Elusimicrobiota at the phylum level decreased in the IGR group, and Verrucomicrobiota abundance decreased following TZT exposure. We found that Patescibacteria abundance decreased in the HFD-induced IGR group, consistent with Lu et al [32]. Also, Patescibacteria was negatively correlated with FPG, 2 h PG, INS, and Tregs, and positively correlated with Th1 and TNF-α levels.…”

Differential Gut Microbiota Compositions Related With the Severity of Major Depressive Disorder

“…Many metabolites produced by gut microbiota are closely related to health ( Lu et al., 2021 ; Zhong et al., 2021 ; Xie et al., 2021 ). Short-chain fatty acids (SCFAs), as the main products of gut microbiota, have been found to change in many diseases such as cardiovascular disease and autism ( Chambers et al., 2018 ; Tran and Mohajeri, 2021 ).…”

The parasitic worm product ES-62 protects the osteoimmunology axis in a mouse model of obesity-accelerated ageing

“…ES-62’s key actions in combating dysregulation of the osteoimmunology axis in male HCD-fed mice focus on slowing the ageing-related myeloid/lymphoid bias and associated loss of B lineage cells, as well as protecting the BM niche by suppressing the mesenchymal skewing towards adipocyte accumulation. These actions are likely interconnected as adipocyte skewing results in the depletion of the osteoblasts (or progenitors) proposed to be important, via their generation of IL-7 and CXCL12 (SDF-1), for B cell differentiation ( 39 ), as well as disrupting the BM niche and inducing pathogenic bone remodelling ( 25 , 69 – 71 ). Given the increasing evidence that LPS-stimulated TLR4/MyD88 signalling is critical in driving both emergency pro-inflammatory myelopoiesis to fight infection and the myeloid/lymphoid skewing associated with (obesity-accelerated) ageing ( 66 ), our working model is that ES-62 harnesses its ability to subvert TLR4 signalling and downregulate MyD88 in order to counteract such dysregulation of HSCs, both in the BM and the periphery.…”

“…Given the increasing evidence that LPS-stimulated TLR4/MyD88 signalling is critical in driving both emergency pro-inflammatory myelopoiesis to fight infection and the myeloid/lymphoid skewing associated with (obesity-accelerated) ageing ( 66 ), our working model is that ES-62 harnesses its ability to subvert TLR4 signalling and downregulate MyD88 in order to counteract such dysregulation of HSCs, both in the BM and the periphery. Moreover, the central role of sensing of LPS ( 66 ), elevated in serum as a consequence of microbiota dysbiosis and loss of gut barrier integrity in each of infection and obesity, conditions associated with chronic inflammation and ageing per se , underlines the key contributions of the TLR4/MyD88 signalling cassette and the gut-osteoimmunology axis in the (dys)regulation of health and well-being over the life-course ( 11 – 14 , 17 – 19 , 25 , 69 – 71 ).…”