DataSheet_1_Do we need to change our perspective about gut biomarkers? A public data mining approach to identify differentially abundant bacteria in intestinal inflammatory diseases.pdf

IntroductionThe gut microbiome is involved in multiple processes that influence host physiology, and therefore, disruptions in microbiome homeostasis have been linked to diseases or secondary infections. Given the importance of the microbiome and the communities of microorganisms that compose it (microbiota), the term biomarkers were coined, which are bacteria correlated with disease states, diets, and the lifestyle of the host. However, a large field in the study of intestinal biomarkers remains unexplored because the bacterial communities associated with a given disease state have not been exactly defined yet.
MethodsHere, we analyzed public data of studies focused on describing the intestinal microbiota of patients with some intestinal inflammatory diseases together with their respective controls. With these analyses, we aimed to identify differentially abundant bacteria between the subjects with the disease and their controls.
ResultsWe found that frequently reported bacteria such as Fusobacterium, Streptococcus, and Escherichia/Shigella were differentially abundant between the groups, with a higher abundance mostly in patients with the disease in contrast with their controls. On the other hand, we also identified potentially beneficial bacteria such as Faecalibacterium and Phascolarctobacterium, with a higher abundance in control patients.
DiscussionOur results of the differentially abundant bacteria contrast with what was already reported in previous studies on certain inflammatory diseases, but we highlight the importance of considering more comprehensive approaches to redefine or expand the definition of biomarkers. For instance, the intra-taxa diversity within a bacterial community must be considered, as well as environmental and genetic factors of the host, and even consider a functional validation of these biomarkers through in vivo and in vitro approaches. With the above, these key bacterial communities in the intestinal microbiota may have potential as next-generation probiotics or may be functional for the design of specific therapies in certain intestinal diseases.

1 引言
肠道微生物组（gut microbiome）参与调控诸多影响宿主生理的过程，因此微生物组稳态失衡与疾病或继发感染密切相关。鉴于微生物组及其组成的微生物群落——微生物群（microbiota）的重要性，“生物标志物（biomarkers）”这一概念被提出，即与宿主疾病状态、饮食及生活方式相关的细菌。然而，由于特定疾病状态相关的细菌群落尚未被精准界定，肠道生物标志物研究仍有大量领域有待探索。
2 方法
本研究针对部分肠道炎性疾病患者及其对应健康对照的肠道微生物群（intestinal microbiota）相关研究公开数据开展分析，旨在甄别疾病组与对照组间丰度存在显著差异的细菌。
3 结果
本研究发现，梭杆菌属（Fusobacterium）、链球菌属（Streptococcus）以及埃希氏菌属/志贺氏菌属（Escherichia/Shigella）等既往常被报道的细菌类群在两组间丰度存在显著差异，且此类细菌在疾病患者体内的丰度普遍高于健康对照。此外，本研究还甄别出粪杆菌属（Faecalibacterium）、考拉杆菌属（Phascolarctobacterium）等潜在有益菌，此类细菌在健康对照体内的丰度更高。
4 讨论
本研究中关于丰度差异细菌的结果与既往部分炎性疾病相关研究的报道存在差异，但本研究强调，应采用更全面的研究方法重新界定或拓展生物标志物的定义。例如，不仅需要考量细菌群落内的类群内多样性，还需纳入宿主的环境与遗传因素，甚至应通过体内（in vivo）及体外（in vitro）实验对这些生物标志物开展功能验证。基于上述思路，肠道微生物群中的这些关键细菌群落有望开发为下一代益生菌，或可用于设计针对特定肠道疾病的专属治疗方案。