Reprogrammed intestinal functions in <i>Astragalus</i> polysaccharide-alleviated osteoporosis: combined analysis of transcriptomics and DNA methylomics demonstrates the significance of the gut–bone axis in treating osteoporosis

Liu, Junsheng; Liu, Liu; Zhang, Guangwen; Peng, Xichun

doi:10.1039/d1fo00113b

Cited by 15 publications

(8 citation statements)

References 27 publications

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“…In rats, OS has been demonstrated to cause intestinal dysfunction. Additionally, reprogramming intestinal function through the gut-bone axis, drugs potentially modulate bone metabolism ( 30 , 31 ). By producing metabolites, which enter the systemic circulation from the gastrointestinal tracts, microorganisms were known to have an impact on bone ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

The genetically predicted causal relationship of inflammatory bowel disease with bone mineral density and osteoporosis: evidence from two-sample Mendelian randomization

Chen

Gao

et al. 2023

Front. Immunol.

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BackgroundMany existing studies indicated that patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), tend to have the risk of low total body bone mineral density (BMD), and are more likely to have osteoporosis (OS). To determine the causal relationship between IBD and bone metabolic disorders, we herein performed a two-sample Mendelian randomization analysis (TSMR) using publicly available summary statistics.MethodsSummary statistics of total body BMD, OS and IBD were downloaded from the Open Genome-Wide Association Study (GWAS), FinnGen consortium and International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). The European and East Asian populations have consisted in this Mendelian Randomization (MR) work. A range of quality control procedures were taken to select eligible instrument SNPs closely associated with total body BMD, OS and IBD. To make the conclusions more reliable, we applied five robust analytical methods, among which the inverse variance weighting (IVW) method acted as the major method. Besides, heterogeneity, pleiotropy and sensitivity were evaluated.ResultsIn the European population, the genetic association of UC on total body BMD (OR=0.97, 95%CI=0.96,0.99, P<0.001) and overall IBD on total body BMD (OR=0.98, 95%CI=0.97,1.00, P=0.013) were significant, while the effect of CD on total body BMD was not significant enough (OR=0.99, 95%CI=0.98,1.00, P=0.085). All of UC, CD and overall IBD can be the genetic risk factor of having OS with pathological fracture (UC: OR=1.13, 95%CI=1.02,1.26, P=0.024, CD: OR=1.14, 95%CI=1.05,1.25, P=0.003, overall IBD: OR=1.13, 95%CI=1.02,1.24, P=0.015). In East Asian groups, only CD had a causal relationship with OS (OR=1.04, 95% CI=1.01,1.07, P=0.019).ConclusionOur study revealed genetically predicted associations between IBD on total body BMD and OS in European and East Asian populations. This work supplemented the results of previous retrospective studies and demonstrated the necessity of BMD monitoring in patients with IBD.

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Section: Discussionmentioning

confidence: 99%

The genetically predicted causal relationship of inflammatory bowel disease with bone mineral density and osteoporosis: evidence from two-sample Mendelian randomization

Chen

Gao

et al. 2023

Front. Immunol.

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“…Studies have shown that APS exerts its anti-inflammatory effect by inhibiting LPS-induced production of TNF-α and IL-8 in intestinal epithelial cells by blocking mitogen-activated protein kinase (MAPK) transcriptional activity (Yuan et al, 2009). In addition to identifying the role of APS through its antiinflammatory and antioxidant properties, recent studies have demonstrated a link between APS and the DNA methylome (Liu et al, 2021). In this study, we verified that APS exerts its antiinflammatory effect on THP-1 macrophages through m 6 A modifications.…”

Section: Discussionmentioning

confidence: 99%

WTAP mediates the anti-inflammatory effect of Astragalus mongholicus polysaccharide on THP-1 macrophages

Long

Lin²,

Zheng³

et al. 2022

Front. Pharmacol.

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Background:Astragalus mongholicus polysaccharides (APS) have anti-inflammatory, antioxidant and immunomodulatory effects. Recent studies have demonstrated the epigenetic regulation of N6-methyladenosine (m6A) in the development of inflammation. However, the effect of APS on m6A modification is unclear. Here, for the first time, we investigate the mechanism of m6A modification in APS regulation of THP-1 macrophage inflammation.Methods: We treated LPS-induced THP-1 macrophages with APS at different concentrations and times, and detected IL-6 mRNA and protein levels by quantitative real-time PCR (qRT-PCR) and western blot, respectively. The m6A modification level was detected by m6A quantification kit. The proteins that regulate m6A modification were screened by western blot. Wilms’ tumor 1-associating protein (WTAP) was overexpressed in APS-treated THP-1 macrophages and the m6A modification level and IL-6 expressions were detected.Results: These findings confirmed that APS significantly abolished LPS-induced IL-6 levels in THP-1 macrophages. Meanwhile, APS reduced m6A modification levels and WTAP gene expression in THP-1 macrophages. Further overexpression of WTAP can significantly reverse APS-induced m6A modification level and IL-6 expression. Mechanistically, APS regulates IL-6 expression through WTAP-mediated p65 nuclear translocation.Conclusion: Overall, our study suggested that WTAP mediates the anti-inflammatory effect of APS by regulating m6A modification levels in THP-1 macrophages. This study reveals a new dimension of APS regulation of inflammation at the epigenetic level.

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“…Recovery of osteoclast differentiation and the calcium signaling pathway might contribute to the improvement of osteoporosis. 116 Other Gut Axis Pathways Involving Prebiotics. Sinha et al introduced the regulation of the intestinal microbiome as a potential adjuvant treatment for certain skin diseases, particularly through studies on oral probiotics, prebiotics, and dietary improvements.…”

Section: Journal Ofmentioning

confidence: 99%

“…APS restored intestinal function in osteoporotic rats by reversing the expression of 53 DEGs. Recovery of osteoclast differentiation and the calcium signaling pathway might contribute to the improvement of osteoporosis …”

Section: Health Benefits Of Prebiotics Through Gut Axis Regulationmentioning

confidence: 99%

Sources, Processing-Related Transformation, and Gut Axis Regulation of Conventional and Potential Prebiotics

Cheng

Kong

Xia

et al. 2022

J. Agric. Food Chem.

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One strategy to achieve a balanced intestinal microbiota is to introduce prebiotics. Some substances present in the diet, such as soybean extracts, koji glycosylceramides, grape extracts, tea polyphenols, and seaweed extracts, can be considered as potential prebiotics, because they can selectively stimulate the proliferation of beneficial bacteria in the intestine. However, the discovery of novel prebiotics also involves advances in screening methods and the use of thermal and non-thermal processing techniques to modify and enhance the properties of beneficial organisms. The health benefits of prebiotics are also reflected by their participation in regulating the microbiota in different gut axes. In the present review, we introduced the field of prebiotics, focusing on potential prebiotic substances, the process of screening potential prebiotics, the transformation of prebiotics by food-processing technologies, and the roles of prebiotics on gut axis regulation, which, it is hoped, will promote the discovery and utilization of novel prebiotics.

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Reprogrammed intestinal functions in Astragalus polysaccharide-alleviated osteoporosis: combined analysis of transcriptomics and DNA methylomics demonstrates the significance of the gut–bone axis in treating osteoporosis

Abstract: Researchers have noted that organ-organ communication between the bone and the intestine has significant effects on bone health and its related diseases. In this study, we collected colonic epithelial tissue...

Cited by 15 publications

References 27 publications

The genetically predicted causal relationship of inflammatory bowel disease with bone mineral density and osteoporosis: evidence from two-sample Mendelian randomization

The genetically predicted causal relationship of inflammatory bowel disease with bone mineral density and osteoporosis: evidence from two-sample Mendelian randomization

WTAP mediates the anti-inflammatory effect of Astragalus mongholicus polysaccharide on THP-1 macrophages

Sources, Processing-Related Transformation, and Gut Axis Regulation of Conventional and Potential Prebiotics

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