Diallo Dramane, Sun Shan, Somboro Anou Moise, Baya Bocar, Kone Amadou, Diarra Bassirou, Nantoume Mohamed, Koloma Isaac, Diakite Mahamadou, Holl Jane, Maiga Almoustapha Issiaka, Seydi Moussa, Theron Grant, Hou Lifang, Fodor Anthony, Maiga Mamoudou
University Clinical Research Center (UCRC) of the University of Sciences, Technics and Technologies of Bamako (USTTB).
Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, North Carolina.
Res Sq. 2023 Aug 11:rs.3.rs-3232670. doi: 10.21203/rs.3.rs-3232670/v1.
Tuberculosis (TB) infection is known to lead to the unbalance of the gut microbiota and act synergistically on the decline of the host immune response, when untreated. Moreover, previous work has found a correlation between dysbiosis in the gut microbiota composition and the use of antibiotics. However, there is a need for an in-depth understanding of the metabolic and immune consequences of antibiotic-related microbiome alterations during first-line TB treatment.
In a longitudinal cohort study, which included TB-infected cohorts and healthy individuals (control group), we studied the anti-TB-related changes in the gut microbiota composition and related functional consequences. Sputum, whole blood and stool samples were collected from participants at four time-points including before (Month-0), during (Month-2), at the end of drug treatment (Month-6) and 9 months after treatment (Month-15). Controls were sampled at inclusion and Month-6. We analyzed the microbiota composition and microbial functional pathways with shotgun metagenomics, analyzed the blood metabolomics using high-performance liquid chromatography (HPLC), and measured the levels of metabolites and cytokines with cytometric bead array.
We found that the gut microbiota of patients infected with TB was different from that of the healthy controls. The gut microbiota became similar to healthy controls after treatment but was still significantly different after 6 months treatment and at the follow up 9 months after treatment. Our data also showed disturbance in the plasma metabolites such as tryptophan and tricarboxylic acids components of patients during TB treatment. Levels of IL-4, IL-6, IL-10, and IFN-γ decreased during treatment and levels were maintained after treatment completion, while IL-17A known to have a strong link with the gut microbiota was highly expressed during treatment period and longer than the 9-month post treatment completion. We found that some fatty acids were negatively correlated with the abundance of taxa. For example, , and HIMB5 species were negatively correlated (rho = -0.6) with the quinolinate production.
Changes in the composition and function of gut microbiota was observed in TB patients before and after treatment compared to healthy controls. The differences persisted at nine months after treatment completion. Alterations in some bacterial taxa were correlated to the changes in metabolite levels in peripheral blood, thus the altered microbial community might lead to changes in immune status that influence the disease outcome and future resistance to infections.
已知未经治疗的结核病（TB）感染会导致肠道微生物群失衡，并协同作用于宿主免疫反应的下降。此外，先前的研究发现肠道微生物群组成的失调与抗生素的使用之间存在关联。然而，有必要深入了解一线抗结核治疗期间抗生素相关微生物组改变的代谢和免疫后果。
在一项纵向队列研究中，该研究包括结核病感染队列和健康个体（对照组），我们研究了肠道微生物群组成的抗结核相关变化及相关功能后果。在四个时间点从参与者收集痰液、全血和粪便样本，包括治疗前（第0个月）、治疗期间（第2个月）、药物治疗结束时（第6个月）和治疗后9个月（第15个月）。对照组在纳入时和第6个月进行采样。我们使用鸟枪法宏基因组学分析微生物群组成和微生物功能途径，使用高效液相色谱（HPLC）分析血液代谢组学，并通过细胞计数珠阵列测量代谢物和细胞因子水平）。
我们发现结核病感染患者的肠道微生物群与健康对照组不同。治疗后肠道微生物群变得与健康对照组相似，但在治疗6个月后和治疗后9个月的随访中仍有显著差异。我们的数据还显示，结核病治疗期间患者的血浆代谢物如色氨酸和三羧酸成分出现紊乱。治疗期间IL-4、IL-6、IL-10和IFN-γ水平下降，治疗完成后水平维持不变，而已知与肠道微生物群有密切联系的IL-17A在治疗期间及治疗完成后9个月以上高表达。我们发现一些脂肪酸与分类群的丰度呈负相关。例如， HIMB5物种与喹啉酸的产生呈负相关（rho = -0.6）。
与健康对照组相比，结核病患者治疗前后肠道微生物群的组成和功能发生了变化。这些差异在治疗完成9个月后仍然存在。一些细菌分类群的改变与外周血代谢物水平的变化相关，因此改变的微生物群落可能导致免疫状态的变化，从而影响疾病结局和未来对感染的抵抗力。
