Association of gut microbiota with bone mineral density in 55 – 65 years old rural Han residents of Taizhou city
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摘要:
目的 了解江苏省泰州市55~65岁汉族农村居民肠道菌群与骨密度之间的关联性,为骨质疏松症的预防提供新的思路。 方法 于2013年3月 — 2018年10月采用整群随机抽样方法抽取泰州队列中依从性和应答率较高的3个自然村中537名55~65岁在泰州市居住 ≥ 20年的汉族农村居民进行问卷调查、体格检查、骨密度测量和粪便检查,并参照世界卫生组织的诊断标准将其分为正常骨密度组、低骨量组和骨质疏松组3组,分析组间菌群的差异以及肠道菌群与骨密度之间的相关性。 结果 泰州市537名55~65岁汉族农村居民中,正常骨密度组207人(38.55 %),低骨量组239人(44.51 %),骨质疏松组91例(16.94 %)。在校正了性别、年龄、体质指数、吸烟情况和饮酒情况等变量后,偏相关分析结果显示,新鲜蔬菜(β = – 0.125)、新鲜水果(β = – 0.101)、肉类(β = – 0.098)和酸奶(β = – 0.033)摄入频次均与骨密度分组呈负相关(均P < 0.05)。与正常骨密度组比较,梭形杆菌、布劳特氏菌、弯曲杆菌、大肠杆菌、链球菌、放线菌、志贺氏菌、厌氧菌、链霉菌和奇异果菌在低骨量组和骨质疏松组的丰度均有所下降,而棒状杆菌、韦洛内拉菌和短链单胞菌在低骨量组和骨质疏松组的丰度则均有所增加(均P < 0.05)。在调整了性别、年龄、体质指数、吸烟情况、饮酒情况、新鲜蔬菜摄入频次、新鲜水果摄入频次、肉类摄入频次和酸奶摄入频次等混杂因素后,多因素非条件logistic回归分析结果显示,大肠杆菌(OR = 0.992,95 % CI = 0.985~0.999)、志贺氏菌(OR = 0.984,95 % CI = 0.970~0.998)、布劳特氏菌(OR = 0.959,95 % CI = 0.924~0.996)和镰刀菌(OR = 0.980,95 % CI = 0.962~0.998)丰度的增加是泰州市55~65岁汉族农村居民低骨量发生的保护因素,粪杆菌丰度的增加(OR = 1.060,95 % CI = 1.006~1.118)是泰州市55~65岁汉族农村居民骨质疏松发生的危险因素,木杆菌丰度的增加(OR = 0.865,95 % CI = 0.763~0.981)是泰州市55~65岁汉族农村居民骨质疏松发生的保护因素。 结论 肠道菌群与骨密度具有相关性,大肠杆菌、志贺氏菌、布劳特氏菌、镰刀菌、粪杆菌和木杆菌丰度的增加均会对泰州市55~65岁汉族农村居民的骨密度造成一定影响。 Abstract:Objective To examine the relationship between intestinal flora and bone mineral density among rural Han residents aged 55 – 65 years in Taizhou city, Jiangsu province for exploring novel approaches to osteoporosis prevention. Methods Using cluster random sampling, we recruited 537 rural Han long term (≥ 20 years) residents aged 55 – 65 years in 3 villages with more compliant followees and high response rate in a cohort for multidisciplinary and multiple diseases research – the Taizhou Longitudinal Study. Questionnaire interview, physical examination, bone density measurement and stool specimen detection were carried out among the selected residents from March 2013 through October 2018. The residents were then assigned into one of the 3 groups with normal bone density, osteopenia and osteoporosis based on bone density measurement according to the diagnostic criteria of World Health Organization. Differences in intestinal flora among the 3 groups and the correlation between intestinal flora and bone density were analyzed. Results Of all the participants, 38.55% (207), 44.51% (239), and 16.94% (91) were assessed with normal bone density, osteopenia, and osteoporosis, respectively. After adjusting for variables such as gender, age, body mass index (BMI), smoking and alcohol drinking, the results of partial correlation analysis showed that intake frequency of fresh vegetables (β = – 0.125), fresh fruits (β = – 0.101), meat (β = – 0.098) ) and yogurt (β = – 0.033) were reversely correlated significantly with bone mineral density grouping (all P < 0.05). Compared with those in the normal bone density group, the intestinal abundances of Clostridium, Blautia, Campylobacter, Escherichia, Streptococcus, Actinomyces, Shigella, Anaerostipes, Streptomyces and Atopobium were significantly decreased in both osteopenia and osteoporosis group; but the intestinal abundances of Corynebacterium, Veillonella and Brevundimonas increased in osteopenia and osteoporosis group (all P < 0.05). After adjusting for confound-ing factors such as gender, age, BMI, smoking, alcohol drinking, and intake frequency of fresh vegetable/fresh fruit/ meat/yogurt, the results of unconditional multivariate logistic regression analysis showed that the increased intestinal relative abundance of Escherichia (odds ratio [OR] = 0.992, 95% confidence interval [95% CI]: 0.985 – 0.999), Shigella (OR = 0.984, 95% CI: 0.970 – 0.998), Blautia (OR = 0.959, 95% CI: 0.924 – 0.996) and Fusicatenibacter (OR = 0.980, 95% CI: 0.962 – 0.998) are protective factors for the occurrence of osteopenia in the residents; the intestinal relative abundance of Faecalibacterium (OR = 1.060, 95% CI: 1.006 – 1.118) is a risk factor for osteoporosis incidence, while that of Mogibacterium (OR = 0.865, 95% CI: 0.763 – 0.981) is a protective factor for osteoporosis incidence. Conclusion In 55 – 65 years old rural Han residents, intestinal flora may associate with bone density; increased intestinal abundance of Escherichia , Shigella, Blautia, Fusicatenibacter, Faecalibacterium, and Mogibacterium could affect bone mineral density of the population. -
Key words:
- bone mineral density /
- gut microbiota /
- correlation analysis /
- rural residents /
- Han nationality
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表 1 泰州市不同组别55~65岁汉族农村居民肠道菌群丰度比较
肠道菌群 标化丰度均值($\bar x \pm s$) 正常骨密度组 低骨量组 骨质疏松组 梭形杆菌 36.26 ± 95.28 15.54 ± 95.23 b 25.15 ± 95.18 b 布劳特氏菌 140.69 ± 141.94 104.15 ± 141.79 b 123.39 ± 141.64 a 弯曲杆菌 13.30 ± 22.04 9.92 ± 22.01 b 11.17 ± 21.99 a 类芽孢杆菌 2.00 ± 2.13 1.86 ± 2.12 1.75 ± 2.12 a 棒状杆菌 10.64 ± 66.14 14.86 ± 66.08 b 11.90 ± 66.30 b 大肠杆菌 1221.74 ± 1697.40 857.20 ± 1695.54 b 863.29 ± 1694.25 b 链球菌 304.55 ± 511.42 183.00 ± 511.06 a 189.47 ± 510.67 b 放线菌 22.59 ± 37.60 9.99 ± 37.58 b 7.52 ± 37.53 b 志贺氏菌 110.76 ± 145.65 78.51 ± 145.50 a 89.67 ± 145.36 b 木杆菌 2.72 ± 2.99 2.20 ± 2.98 1.21 ± 2.97 b 厌氧菌 6.21 ± 9.72 5.31 ± 9.70 a 4.61 ± 9.69 a 链霉菌 7.64 ± 10.11 7.35 ± 10.07 a 3.23 ± 10.03 b 莱克莱西亚菌 12.67 ± 16.12 5.92 ± 16.04 13.23 ± 15.96 b 甲烷八叠球菌 5.26 ± 8.12 6.01 ± 8.01 3.12 ± 8.08 b 艰难梭菌 110.64 ± 196.28 115.06 ± 196.12 89.03 ± 195.95 a 戈多尼杆菌 15.23 ± 25.61 11.45 ± 25.58 12.43 ± 25.54 a 葡萄球菌 3.84 ± 14.77 4.66 ± 14.76 3.13 ± 14.74 b 克雷伯氏菌 1421.87 ± 2634.72 1267.18 ± 1235.58 1471.18 ± 2630.34 a 粪杆菌 1537.13 ± 1800.92 1632.86 ± 1798.99 2128.64 ± 1797.07 a 乳酸菌 86.55 ± 324.32 67.04 ± 324.14 104.76 ± 323.96 a 嗜胆菌 59.45 ± 130.49 57.58 ± 130.38 36.35 ± 130.23 a 大球藻菌 118.95 ± 222.79 71.77 ± 222.52 50.23 ± 222.26 a 单杆菌 2.67 ± 3.09 2.04 ± 3.08 1.29 ± 3.08 a 寄生虫菌 45.01 ± 54.74 19.16 ± 54.64 14.46 ± 54.53 a 链状杆菌 6.28 ± 62.41 19.48 ± 26.37 b 7.31 ± 62.34 多雷亚菌 65.07 ± 68.34 46.67 ± 68.26 b 48.77 ± 68.19 酪酸球菌 132.25 ± 178.55 94.83 ± 178.39 b 91.41 ± 178.22 毛单胞菌 35.45 ± 601.51 363.48 ± 599.85 b 84.17 ± 598.13 普罗维登西亚菌 14.82 ± 403.32 105.45 ± 402.80 b 25.89 ± 402.25 吉米格菌 292.27 ± 504.78 263.89 ± 504.39 b 444.78 ± 506.01 沙门氏菌 14.39 ± 13.07 13.40 ± 13.05 b 14.69 ± 13.03 瘤胃球菌 289.96 ± 325.15 275.94 ± 324.81 a 324.46 ± 392.04 科林塞拉 196.12 ± 418.26 127.89 ± 418.32 b 183.69 ± 418.01 明串珠菌 4.97 ± 7.83 4.69 ± 7.79 a 4.67 ± 7.75 罗西亚菌 12.36 ± 19.29 9.16 ± 17.27 a 12.30 ± 19.25 小颗粒菌 109.90 ± 143.13 109.23 ± 142.98 a 108.49 ± 142.83 梭菌 70.89 ± 188.10 51.91 ± 188.00 a 30.86 ± 187.89 不动杆菌 30.05 ± 236.62 129.72 ± 236.48 b 22.85 ± 236.33 奇异果菌 8.29 ± 17.69 4.90 ± 17.67 a 4.23 ± 17.65 a 艾森伯格菌 9.68 ± 13.72 8.57 ± 13.71 a 12.51 ± 13.69 a 嗜酸杆菌 171.59 ± 232.52 175.22 ± 232.28 a 152.53 ± 232.04 a 韦洛内拉菌 98.30 ± 568.60 190.09 ± 568.31 a 134.88 ± 568.03 a 短链单胞菌 42.97 ± 1060.92 610.91 ± 1058.20 a 83.76 ± 1055.96 b 克罗诺杆菌 28.12 ± 381.32 25.19 ± 381.09 b 141.61 ± 380.85 b 注:各组间比较,a P < 0.05;b P < 0.01。 -
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