Correlation between intestinal flora and clinical symptoms in patients with schizophrenia
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摘要:
目的 探究精神分裂症菌群结构特征与临床症状的相关性。 方法 纳入2018年10月—2019年6月合肥市第四人民医院收治的精神分裂症患者急性发作期(A组)32例, 缓解期(B组)30例,健康对照(C组)34人。运用16SrRNA技术分析菌群差异及与临床症状的相关性。 结果 (1) 另枝菌属A组丰度高于C组(F=2.575,P=0.017),硫杆菌属A组丰度低于C组(F=3.940,P=0.023);巨球型菌属A组、B组丰度高于C组(F=11.720,P < 0.001),毛螺菌属、粪球菌属A组、B组丰度低于C组(F=4.279、3.670,均P < 0.05);拟杆菌属、嗜血杆菌属、酪酸梭菌属A组丰度高于B组(F=2.977、4.840、2.655,均P < 0.05),琥珀酸弧菌属A组丰度低于B组(F=6.190,P=0.003)。(2)小杆菌属与抑郁因子呈负相关(r=-0.269,P=0.034);巨单胞菌属与阳性和阴性症状量表(PANSS)总分呈正相关(r=0.291,P=0.022);拟杆菌属与阳性因子成正相关(r=0.282,P=0.029)。 结论 精神分裂症急性发作期和缓解期菌群结构改变,且部分菌群相对丰度与临床症状相关。 Abstract:Objective This study aimed to explore the correlation between the structural characteristics of schizophrenia flora and clinical symptoms. Methods Patients who were diagnosed with schizophrenia in the fourth hospital in Hefei from October 2018 to June 2019 were included in this study: 32 patients in the acute stage (group A), 30 in the remission stage (group B) and 34 in the healthy control group (group C). The 16SrRNA technique was used to analyse the difference of bacterial flora and its correlation with clinical symptoms. Results (1) The abundance of other mycobacteria in group A was higher than that in group C (F=2.575, P=0.017), whereas the abundance of thiobacillus in group A was lower than that in group C (F=3.940, P=0.023). The abundance of macrococcidia in groups A and B was higher than that of group C (F=11.720, P < 0.001), and the abundance of trichoderma and coprococcus in groups A and B was lower than that of group C (F=4.279、3.670, all P < 0.05). The abundance of Bacteroidetes, haemophilus and Clostridium tyrosine in group A was higher than that in group B (F=2.977, 4.840; F=2.655, P < 0.05), and the abundance of vibrio succinate was lower than that of group B (F=6.190, P=0.003). (2) Microbacilli were negatively correlated with depression factors (r=-0.269, P=0.034). Macrosomonas was positively correlated with the total PANSS score (r=0.291, P=0.022). Bacteroidetes was positively correlated with positive factors (r=0.282, P=0.029). Conclusion The structural changes of the microflora in the acute and remission stages of schizophrenia and the relative abundance of some microflora were correlated with clinical symptoms. -
Key words:
- Schizophrenia /
- Intestinal flora /
- High-throughput sequencing /
- Clinical symptoms
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表 1 精神分裂症患者发作期与缓解期PANSS评分比较(x±s,分)
组别 例数 阳性症状 阴性症状 认知因子 兴奋因子 抑郁因子 总分 A组 32 15.44±4.77 19.44±5.09 10.78±2.14 10.41±2.54 4.28±2.23 71.44±8.20 B组 30 9.03±2.11 13.67±4.40 6.83±1.86 5.70±1.06 3.20±0.48 45.67±6.64 t值 6.764 4.788 7.776 9.417 2.674 13.639 P值 <0.001 <0.001 <0.001 <0.001 0.011 <0.001 表 2 3组肠道菌群的Alpha多样性指数比较(x±s)
组别 例数 chao指数 ace指数 observed指数 simpson指数 shannon指数 coverage指数 A组 32 338.53±73.88 335.57±73.88 278.71±67.13 0.14±0.12 3.05±0.66 1.00±0.00 B组 30 334.52±89.20 334.84±86.34 278.28±80.92 0.12±0.76 3.10±0.64 1.00±0.00 C组 34 333.46±75.74 330.79±68.62 268.56±69.66 0.12±0.08 3.08±0.58 1.00±0.01 F值 0.172 0.153 0.153 0.008 0.040 0.434 P值 0.859 0.860 0.778 0.998 0.994 0.532 表 3 肠道菌群相对丰度与临床症状的相关性(r值)
肠道菌群 阳性因子 阴性因子 认知因子 兴奋因子 抑郁因子 总分 小杆菌属 -0.180 -0.230 -0.217 -0.153 -0.269a -0.123 嗜黏蛋白阿克曼病菌属 0.070 0.209 0.138 0.113 0.076 0.157 考拉杆菌属 0.137 0.030 0.125 0.068 0.123 0.013 瘤胃球菌属 0.141 0.158 0.086 0.121 -0.097 0.208 罗斯氏菌属 0.131 -0.129 -0.058 0.009 0.080 -0.111 巨单胞菌属 0.090 0.226 0.204 0.028 -0.196 0.291a 埃希氏杆菌属 0.181 -0.145 -0.053 0.068 -0.215 0.091 粪杆菌属 0.062 0.075 -0.020 -0.020 0.136 -0.054 普氏菌属 -0.197 -0.249 -0.247 -0.080 -0.215 -0.120 拟杆菌属 0.282a 0.082 0.103 0.004 0.082 0.123 注:aP < 0.05。 -
[1] VOS T, ABAJOBIRMA, ABBAFATI C, et al. GBD 2016 disease and injury incidence and prevalence collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016[J]. Lancet, 2017, 390(10100): 1211-1259. doi: 10.1016/S0140-6736(17)32154-2 [2] SCRIVEN M, DINAN T G, CRYAN J F, et al. Neuropsychiatric disorders: Influence of gut microbe to brain signalling[J]. Diseases, 2018, 6(3): 78. doi: 10.3390/diseases6030078 [3] YANG B, WEI J, JU P, et al. Effects of regulating intestinalmicrobiota on anxiety symptoms: A systematic review [J]. Gen Psychiatr, 2019, 32(2): e100056. doi: 10.1136/gpsych-2019-100056 [4] 周梦玲, 李婷, 倪敬年, 等. 帕金森病肠道菌群与中医证候的相关性研究[J]. 中华中医药杂志, 2019, 34(5): 2274-2278. https://www.cnki.com.cn/Article/CJFDTOTAL-BXYY201905093.htm [5] 卢燕, 刘占利. 肠道菌群和癫痫相关性研究进展[J]. 中华全科医学, 2018, 16(9): 1550-1553, 1569. https://www.cnki.com.cn/Article/CJFDTOTAL-SYQY201809040.htm [6] SHEN Y, XU J, LI Z, et al. Analysis of gut microbiota diversity and auxiliary diagnosis as a biomarker in patients with schizophrenia: A crosssectional study [J]. Schizophr Res, 2018, 197(18): 470-477. http://europepmc.org/abstract/MED/29352709 [7] 许金添. 精神分裂症患者肠道微生物群落多样性研究[D]. 北京: 中国科学院大学, 2018. [8] 张言武, 白丽君, 程强, 等. 精神分裂症发作期与缓解期肠道菌群高通量测序分析[J]. 中国神经精神疾病杂志, 2018, 44(12): 705-709. doi: 10.3969/j.issn.1002-0152.2018.12.001 [9] SCHWARZ E, MAUKONEN J, HYYTIÄINEN T, et al. Analysis of microbiota in first episode psychosis identifies preliminary associations with symptom severity and treatment response[J]. Schizophr Res, 2018, 192: 398-403. doi: 10.1016/j.schres.2017.04.017 [10] NGUYEN T T, KOSCIOLEK T, MALDONADO Y, et al. Differences in gut microbiome composition between persons with chronic schizophrenia and healthy comparison subjects[J]. Schizophr Res, 2019, 204: 23-29. doi: 10.1016/j.schres.2018.09.014 [11] 武月霞, 肠道微生态结构、人格、认知情绪调节与抑郁症的相关性研究[D]. 银川: 宁夏医科大学, 2019. [12] 张现伟, 张飞, 侯广军, 等. 先天性巨结肠儿童肠道菌群特异性变化[J]. 湖南师范大学自然科学学报, 2019, 42(4): 53-58, 65. https://www.cnki.com.cn/Article/CJFDTOTAL-HNSZ201904008.htm [13] MORRISON D J, PRESTON T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism[J]. Gut microbes, 2016, 7(3): 189-200. doi: 10.1080/19490976.2015.1134082 [14] KOH A, DE VADDER F, KOVATCHEVA-DATCHARY P. From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites[J]. Cell, 2016, 165(6): 1332-1345. doi: 10.1016/j.cell.2016.05.041 [15] LOUIS P, FLINT H J. Formation of propionate and butyrate by the human colonic microbiota[J]. Environ Microbiol, 2017, 19(1): 29-41. doi: 10.1111/1462-2920.13589 [16] 申变红, 陶云海, 朱春燕. 肠道菌群比例在精神分裂症发病中的作用及其与炎症因子的关系[J]. 中华全科医学, 2018, 16(2): 276-278. https://www.cnki.com.cn/Article/CJFDTOTAL-SYQY201802033.htm [17] GAO L, LI J, ZHOU Y, et al. Effects of baicalein on cortical proinflammatory cytokines and the intestinal microbiome in senescence accelerated mouse prone 8[J]. ACS Chem Neurosci, 2018, 9(7): 1714-1724. doi: 10.1021/acschemneuro.8b00074 [18] SLYEPCHENKO A, MAES M, JACKA F N, et al. Gut microbiota, bacterial translocation, and interactions with diet: Pathophysiological links between major depressive disorder and noncommunicable medical comorbidities[J]. Psychother Psychosom, 2017, 86(1): 31-46. doi: 10.1159/000448957 [19] MEI C, YANG W, WEI X, et al. The unique microbiome and innate immunity during pregnancy[J]. Front Immunol, 2019, 10: 2886. doi: 10.3389/fimmu.2019.02886