Effect of four-week intensive anti-tuberculous drug therapy on intestinal micro-ecology in patients with tuberculosis
SUN Yu-xia1, ZHAO Shan-liang2, LIU Jia-hong3, ZHANG Jiang-wen1, ZHANG Chao1, MA Ai-guo1
1. School of Public Health, Qingdao University, Qingdao, Shangdong 266023, China; 2. The People's Hospital of Linyi City, Linyi, Shandong 276000, China; 3. Lung Disease Research Institute, Qingdao Central Hospital, Qingdao, Shandong 266042, ChinaCorresponding
Abstract:Objective To analyze the effect of four-week intensive anti-tuberculosis drug treatment on intestinal micro-ecology of tuberculosis patients. Methods We collected stool samples from 10 patients with four-week intensive anti-tuberculosis treatment and 10 healthy controls in a hospital in Qingdao city. The total bacterial genomic DNA was extracted, and the V3-V4 hypervariable region in 16S rDNA gene sequence was amplified by PCR. High-throughput sequencing was performed on Illumina Miseq platform. The sequences were clustered into Operational Taxonomic Unit(OTU)and annotated with species. Alpha diversity was analyzed to describe richness and species diversity of the samples. The difference of bacterial flora structure between the two groups was observed by principal coordinate analysis. The difference of microbial community structure was described by comparing the relative abundance of species at phylum level and genus level. In addition, the bacteria with significant difference between the two groups were identified by line discriminant analysis effect size. The microbial diversity index of the two groups was compared by Mann-Whitney U test. Results Chao1 index and Ace index of Alpha diversity in the four-week anti-tuberculosis treatment group were (140.13±34.73) and (145.18±30.74) respectively, which were significantly lower than those of the control group((196.56±37.12), (197.62±31.76); U=13.000, P=0.004; U=11.000, P=0.002). The Shannon index of the anti-tuberculosis treatment group was (2.31±0.57), which was slightly lower than that of the control group (2.89±0.46), but no statistically significant difference was observed(U=30.000, P=0.143). PCoA analysis based on binary jaccard showed significant differences in the overall flora structure between the two groups. The composition of intestinal flora changed in the four-week anti-tuberculosis treatment group compared with the control group. The relative abundance of Frimicutes and Lachnospiraceae was significantly lower than that in the control group (46.4% vs. 72.4%, χ2=5.491, P=0.019; 72.4% vs. 43.1%, χ2=5.851, P=0.016), while the relative abundance of Bacteroidetes and Bacteroides was significantly higher than that in the control group(39.0% vs. 18.8%, χ2=4.166, P=0.041; 31.4% vs. 10.3%, χ2=7.406, P=0.007). Conclusions The diversity of intestinal flora was decreased and the structure of intestinal flora was obviously unbalanced with four-week intensive anti-tuberculosis drug therapy. The abundance of Lachnospiraceae was decreased, while genus Bacteroides was increased.
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