Reproduction Materials for: Nutrition, Inflammation, and the Gut Microbiota among Outpatients with Active Tuberculosis Disease in India

<p><strong>PI-provided abstract</strong>: India has the highest rates of tuberculosis (TB) globally and a high prevalence of malnutrition; however, the interplay between host nutritional status, inflammation, and the gut microbiome in active tuberculosis disease (ATBD) is less well-studied. We examined differences in gut microbial composition and diversity based on undernutrition and inflammation status among outpatients with ATBD at the time of treatment initiation. During this exploratory cross-sectional study, outpatients (N532) with ATBD (confirmed by Xpert MTB/RIF) were enrolled in anti-TB treatment initiated at a hospital in rural southern India. The 16S rRNA sequencing was used to assess the composition of the gut microbiome. We assessed multiple markers of nutritional status, including micronutrient status concentrations (vitamin D[25(OH)D], vitamin B12, ferritin), anthropometry (body mass index, mid-upper arm circumference, and height), and C-reactive protein (CRP), as indicators of inflammation. We found that 25(OH)D was positively associated with the relative abundance of Oscillospira spp., a butyrate-producing genus linked with anti-inflammation effects, and that ferritin was positively associated with Proteobacteria taxa, which have been associated with worse inflammation in other studies. Finally, we found a greater abundance of inflammation-associated taxa from the Proteobacteria phylum and lower alpha-diversity indices among those who were underweight or who had low mid-upper arm circumference or short stature. In summary, we found differences in the gut microbiota composition and diversity among those with undernutrition compared with those with adequate nutrition status at the time of initiation of treatment among patients with ATBD in India. Clinical implications of these findings will need to be examined by larger longitudinal studies.</p>

项目负责人（Principal Investigator, PI）提供的摘要：印度是全球结核病（tuberculosis, TB）发病率最高的国家，同时营养不良患病率居高不下；然而目前针对活动性结核病（active tuberculosis disease, ATBD）患者体内宿主营养状态、炎症反应与肠道菌群之间的相互作用，相关研究仍较为匮乏。本探索性横断面研究旨在探讨印度南部农村某医院启动抗结核治疗的活动性结核病门诊患者中，基于营养不良与炎症状态的肠道菌群组成及多样性差异。本研究共纳入经Xpert MTB/RIF检测确认的活动性结核病门诊患者532例，均在该院启动抗结核治疗。采用16S rRNA测序技术对肠道菌群组成进行分析，并评估多项营养状态标志物：包括微量营养素浓度指标[维生素D[25(OH)D]、维生素B12、铁蛋白]、人体测量学指标[体重指数、上臂围、身高]，以及作为炎症标志物的C反应蛋白（C-reactive protein, CRP）。研究发现，25(OH)D与产丁酸且具有抗炎作用的Oscillospira菌属（Oscillospira spp.）的相对丰度呈正相关；而铁蛋白与变形菌门（Proteobacteria）类群呈正相关，该类群在既往研究中与更严重的炎症反应相关。此外，我们观察到，体重偏低、上臂围偏小或身材矮小的患者，其体内变形菌门中与炎症相关的类群丰度更高，而α多样性指数更低。综上，在印度的活动性结核病患者启动抗结核治疗时，与营养状态良好者相比，营养不良患者的肠道菌群组成与多样性存在显著差异。该研究结果的临床意义尚需更大规模的纵向研究进一步验证。