青海成年痰检阳性与阴性活动性肺结核患者的肠道菌群差异性

Study on the Difference of Intestinal Flora for Active Pulmonary Tuberculosis Adult Patients Between Sputum Positive and Sputum Negative in Qinghai Province

目的观测青海成年痰检阳性与阴性活动性肺结核患者的肠道菌群差异性。方法选取青海成年痰检阳性活动性肺结核患者14例、痰检阴性活动性肺结核患者12例,采用16S rDNA基因测序技术检测两组受试对象的粪便样本,分析其肠道菌群差异,以及门和属水平上的物种组成和丰度差异。采用线性判别分析效应量法(LDA Effect Size,LEfSe)判断特定菌群是否可以作为区分痰检阳性与阴性患者的生物标志物。结果肠道菌群差异:α多样性分析结果表明,痰检阳性组的肠道菌群物种丰富度(Chao1指数,ACE指数)和多样性(Shannon指数,Simpson指数)与痰检阴性组差异无统计学意义(P>0.05);β多样性分析显示,痰检阳性组与阴性组多样性差异无统计学意义(P>0.05)。门和属水平上的物种组成和丰度差异:门水平上,共发现一个差异菌门,即痰检阴性肺结核组迷踪菌门(Elusimicrobia)相对丰度低于痰检阳性组(0 vs 0.02%,P<0.05);属水平上,共发现13个差异菌属,相对丰度较高且有差异的为萨特氏菌属(Sutterella),其相对丰度值在痰检阴性肺结核组的分布高于痰检阳性组(0.33%vs 0.05%,P<0.05)。线性判别分析结果:经LEfSe分析筛选出可能解释阴性组与阳性组差异的肠道菌群为红球菌属(Rhodococcus)与诺卡氏菌科(Nocardiaceae)。结论青海成年痰检阳性与阴性活动性肺结核患者的肠道菌群的多样性和丰富度无差异性,但菌群构成差异显著,特定红球菌属与诺卡氏菌科菌群可作为潜在生物标志物。

Objective To analyze the diference of intestinal flora between sputum positive and sputum negative pulmonary tuberculosis patients.Methods From December 2021 to June 2022,we selected 26 patients diagnosed as newly treated active pulmonary tuberculosis in the 4th People's Hospital of Qinghai Province.There were 14 active pulmonary tuberculosis patients with positive sputum test and 12 patients with negative sputum test.16S rDNA gene sequencing was used to detect the feces of the two groups of participants for analyzing the diversity and richness difference of intestinal flora between the two groups,as well as the species composition and abundance difference at the phylum and genus levels.LDA Effect Size(LEfSe)analysis was used to explore potential intestinal flora which could be used as biomarkers to distinguish sputum positive patients from negative patients.Results Intestinal microflora difference:α Diversity analysis showed that there was no significant difference in species richness(Chaol Index,ACE Index)and diversity(Shannon Index,Simpson Index)of intestinal flora between the sputum positive group and the negative group(P>0.05);β Diversity analysis showed that there was no significant difference between the two groups(P>0.05).Species composition and abundance differences at the phylum and genus levels:At the phylum,the relative abundance of Elusimicrobia in the sputum negative pulmonary tuberculosis group was lower than that in the sputum positive group(0 vs 0.02%,P<0.05).At the genus,13 different bacteria were found,such as the relative abundance of Sutterella was higher in the sputum negative group than that in the sputum positive group(0.33%vs 0.05%,P<0.05).LEfSe results:Rhodococcus and Nocardiaceae are potential species to explain the difference between the sputum negative group and the sputum positive group through LEfSe analysis.Conclusion The composition of the intestinal flora was significantly different between sputum negative active pulmonary tuberculosis patients and sputum positive active pulmonary tuberculosis patients,while there was no obvious difference in richness and diversity of intestinal flora between the two groups.And we found Rhodococcus and Nocardiaceae might be the potential biomarkers between two groups.