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Calcified Tissue International

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01.04.2020 | Original Research

Neuropeptide Y1 Receptor Antagonist Alters Gut Microbiota and Alleviates the Ovariectomy-Induced Osteoporosis in Rats

verfasst von: Weixin Xie, Yi Han, Fan Li, Xiyao Gu, Diansan Su, Weifeng Yu, Zhanchun Li, Jie Xiao

Erschienen in: Calcified Tissue International | Ausgabe 4/2020

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Abstract

A plethora of evidence has suggested that gut microbiota is involved in the occurrence and development of postmenopausal osteoporosis (PMO). It has been suggested that neuropeptide Y (NPY) modulates the bone metabolism through Y1 receptor (Y1R), and might be associated with gut microbiota. The present study aims to evaluate the anti-osteoporotic effects of Y1R antagonist and to investigate the potential mechanism by which Y1R antagonist regulates gut microbiota. In this study, eighteen female rats were randomly divided into three groups: the sham surgery (SHAM) group, the ovariectomized (OVX) group, and OVX+BIBO3304 group. After 6 weeks following surgery, Y1R antagonist BIBO3304 was administered to the rats in OVX+BIBO3304 group for 7 days. The bone microstructure and serum biochemical parameters were measured at 12 weeks after operation. The differences in the gut microbiota were analyzed by 16S rDNA gene sequencing. Heat-map and Spearman’s correlation analyses were constructed to investigate the correlations between microbiota and bone metabolism-related parameters. The results indicated that OVX+BIBO3304 group showed significantly higher BMD, BV/TV, Tb.Th, Tb.N, Conn.D, and serum Ca²⁺ level than those in OVX group. Additionally, Y1R antagonist changed the gut microbiota composition with lower Firmicutes/Bacteroidetes ratio and higher proportions of some probiotics, including Lactobacillus. The correlation analysis showed that the changes of gut microbiota were closely associated with bone microstructure and serum Ca²⁺ levels. Our results suggested that Y1R antagonist played an anti-osteoporotic effect and regulated gut microbiota in OVX rats, indicating the potential to utilize Y1R antagonist as a novel treatment for PMO.

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Andoh A, Kuzuoka H, Tsujikawa T, Nakamura S, Hirai F, Suzuki Y, Matsui T, Fujiyama Y, Matsumoto T (2012) Multicenter analysis of fecal microbiota profiles in Japanese patients with Crohn's disease. J Gastroenterol 47:1298–1307CrossRef

Brzozowska MM, Sainsbury A, Eisman JA, Baldock PA, Center JR (2013) Bariatric surgery, bone loss, obesity and possible mechanisms. Obes Rev 14:52–67CrossRef

Tojo R, Suárez A, Clemente MG, de los Reyes-Gavilán CG, Margolles A, Gueimonde M, Ruas-Madiedo P (2014) Intestinal microbiota in health and disease: role of bifidobacteria in gut homeostasis. World J Gastroenterol 20:15163–15176CrossRef

Stotzer PO, Johansson C, Mellström D, Lindstedt G, Kilander AF (2003) Bone mineral density in patients with small intestinal bacterial overgrowth. Hepatogastroenterology 50:1415–1418PubMed

Sjögren K, Engdahl C, Henning P, Lerner UH, Tremaroli V, Lagerquist MK, Bäckhed F, Ohlsson C (2012) The gut microbiota regulates bone mass in mice. J Bone Miner Res 27:1357–1367CrossRef

Li JY, Chassaing B, Tyagi AM et al (2016) Sex steroid deficiency-associated bone loss is microbiota dependent and prevented by probiotics. J Clin Invest 126:2049–2063CrossRef

Morales-Medina JC, Dumont Y, Quirion R (2010) A possible role of neuropeptide Y in depression and stress. Brain Res 1314:194–205CrossRef

Imai S, Matsusue Y (2002) Neuronal regulation of bone metabolism and anabolism: calcitonin gene-related peptide-, substance P-, and tyrosine hydroxylase-containing nerves and the bone. Microsc Res Tech 58:61–69CrossRef

Lundberg P, Allison SJ, Lee NJ et al (2007) Greater bone formation of Y2 knockout mice is associated with increased osteoprogenitor numbers and altered Y1 receptor expression. J Biol Chem 282:19082–19091CrossRef

10.

Igwe JC, Jiang X, Paic F, Ma L, Adams DJ, Baldock PA, Pilbeam CC, Kalajzic I (2009) Neuropeptide Y is expressed by osteocytes and can inhibit osteoblastic activity. J Cell Biochem 108:621–630CrossRef

11.

Lee NJ, Doyle KL, Sainsbury A, Enriquez RF, Hort YJ, Riepler SJ, Baldock PA, Herzog H (2010) Critical role for Y1 receptors in mesenchymal progenitor cell differentiation and osteoblast activity. J Bone Miner Res 25:1736–1747CrossRef

12.

Baldock PA, Allison SJ, Lundberg P et al (2007) Novel role of Y1 receptors in the coordinated regulation of bone and energy homeostasis. J Biol Chem 282:19092–19102CrossRef

13.

Schéle E, Grahnemo L, Anesten F, Hallén A, Bäckhed F, Jansson JO (2013) The gut microbiota reduces leptin sensitivity and the expression of the obesity-suppressing neuropeptides proglucagon (Gcg) and brain-derived neurotrophic factor (Bdnf) in the central nervous system. Endocrinology 154:3643–3651CrossRef

14.

El Karim IA, Linden GJ, Orr DF, Lundy FT (2008) Antimicrobial activity of neuropeptides against a range of micro-organisms from skin, oral, respiratory and gastrointestinal tract sites. J Neuroimmunol 200:11–16CrossRef

15.

Quach D, Britton RA (2017) Gut microbiota and bone health. Adv Exp Med Biol 1033:47–58CrossRef

16.

Zhang ZM, Li ZC, Jiang LS, Jiang SD, Dai LY (2010) Micro-CT and mechanical evaluation of subchondral trabecular bone structure between postmenopausal women with osteoarthritis and osteoporosis. Osteoporos Int 21:1383–1390CrossRef

17.

Caporaso JG, Kuczynski J, Stombaugh J et al (2010) QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7:335–336CrossRef

18.

Campos-Obando N, Koek WNH, Hooker ER, van der Eerden BC, Pols HA, Hofman A, van Leeuwen JP, Uitterlinden AG, Nielson CM, Zillikens MC (2017) Serum phosphate is associated with fracture risk: the rotterdam study and MrOS. J Bone Miner Res 32:1182–1193CrossRef

19.

Morris HA, O’Loughlin PD, Anderson PH (2010) Experimental evidence for the effects of calcium and vitamin D on bone: a review. Nutrients 2:1026–1035CrossRef

20.

Burcelin R, Brunner H, Seydoux J, Thorensa B, Pedrazzini T (2001) Increased insulin concentrations and glucose storage in neuropeptide Y Y1 receptor-deficient mice. Peptides 22:421–427CrossRef

21.

Kushi A, Sasai H, Koizumi H, Takeda N, Yokoyama M, Nakamura M (1998) Obesity and mild hyperinsulinemia found in neuropeptide Y-Y1 receptor-deficient mice. Proc Natl Acad Sci USA 95:15659–15664CrossRef

22.

Yu W, Zhu C, Xu W, Jiang L, Jiang S (2016) Neuropeptide Y1 receptor regulates glucocorticoid-induced inhibition of osteoblast differentiation in murine MC3T3-E1 cells via ERK signaling. Int J Mol Sci 17:2150CrossRef

23.

Qin J, Li R, Raes J et al (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464:59–65CrossRef

24.

Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA (2005) Diversity of the human intestinal microbial flora. Science 308:1635–1638CrossRef

25.

Murphy EF, Cotter PD, Healy S et al (2010) Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut 59:1635–1642CrossRef

26.

Magrone T, Jirillo E (2013) The interaction between gut microbiota and age-related changes in immune function and inflammation. Immun Ageing 10:31CrossRef

27.

Kim KA, Gu W, Lee IA, Joh EH, Kim DH (2012) High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLoS ONE 7:e47713CrossRef

28.

Kim KW, Kim HR, Kim BM, Cho ML, Lee SH (2015) Th17 cytokines regulate osteoclastogenesis in rheumatoid arthritis. Am J Pathol 185:3011–3024CrossRef

29.

McCabe LR, Irwin R, Tekalur A, Evans C, Schepper JD, Parameswaran N, Ciancio M (2019) Exercise prevents high fat diet-induced bone loss, marrow adiposity and dysbiosis in male mice. Bone 118:20–31CrossRef

30.

Li C, Huang Q, Yang R, Dai Y, Zeng Y, Tao L, Li X, Zeng J, Wang Q (2019) Gut microbiota composition and bone mineral loss-epidemiologic evidence from individuals in Wuhan, China. Osteoporos Int 30:1003–1013CrossRef

31.

Whisner CM, Martin BR, Nakatsu CH, McCabe GP, McCabe LD, Peacock M, Weaver CM (2014) Soluble maize fibre affects short-term calcium absorption in adolescent boys and girls: a randomised controlled trial using dual stable isotopic tracers. Br J Nutr 112:446–456CrossRef

32.

Bach Knudsen KE, Serena A, Canibe N, Juntunen KS (2003) New insight into butyrate metabolism. Proc Nutr Soc 62:81–86CrossRef

33.

Domon-Dell C, Wang Q, Kim S, Kedinger M, Evers BM, Freund JN (2002) Stimulation of the intestinal Cdx2 homeobox gene by butyrate in colon cancer cells. Gut 50:525–529CrossRef

34.

Xu X, Jia X, Mo L, Liu C, Zheng L, Yuan Q, Zhou X (2017) Intestinal microbiota: a potential target for the treatment of postmenopausal osteoporosis. Bone Res 5:17046CrossRef

35.

Wang M, Zhang X, Wang Y et al (2018) Metabonomic strategy for the detection of metabolic effects of probiotics combined with prebiotic supplementation in weaned rats. RSC Adv 8:5042–5057CrossRef

36.

Vemuri R, Shinde T, Gundamaraju R, Gondalia SV, Karpe AV, Beale DJ, Martoni CJ, Eri R (2018) Lactobacillus acidophilus DDS-1 modulates the gut microbiota and improves metabolic profiles in aging mice. Nutrients 10:E1255CrossRef

37.

Britton RA, Irwin R, Quach D, Schaefer L, Zhang J, Lee T, Parameswaran N, McCabe LR (2014) Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized mouse model. J Cell Physiol 229:1822–1830CrossRef

38.

Zhang J, Motyl KJ, Irwin R, MacDougald OA, Britton RA, McCabe LR (2015) Loss of bone and Wnt10b expression in male type 1 diabetic mice is blocked by the probiotic Lactobacillus reuteri. Endocrinology 156:3169–3182CrossRef

39.

Ohlsson C, Engdahl C, Fåk F, Andersson A, Windahl SH, Farman HH, Movérare-Skrtic S, Islander U, Sjögren K (2014) Probiotics protect mice from ovariectomy-induced cortical bone loss. PLoS ONE 9:e92368CrossRef

40.

Narva M, Nevala R, Poussa T, Korpela R (2004) The effect of Lactobacillus helveticus fermented milk on acute changes in calcium metabolism in postmenopausal women. Eur J Nutr 43:61–68CrossRef

Titel: Neuropeptide Y1 Receptor Antagonist Alters Gut Microbiota and Alleviates the Ovariectomy-Induced Osteoporosis in Rats
verfasst von: Weixin Xie
Yi Han
Fan Li
Xiyao Gu
Diansan Su
Weifeng Yu
Zhanchun Li
Jie Xiao
Publikationsdatum: 01.04.2020
Verlag: Springer US
Erschienen in: Calcified Tissue International / Ausgabe 4/2020
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-019-00647-5

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Neuropeptide Y1 Receptor Antagonist Alters Gut Microbiota and Alleviates the Ovariectomy-Induced Osteoporosis in Rats

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