文章：Intestinal Microbiota Distinguish Gout Patients from Healthy Humans

杂志：Scientific Reports

时间：2016

链接：http://www.nature.com/articles/srep20602#t2

研究样本：

      总共83个样本，分成分析组（35例痛风样本、33例正常样本）和验证组（6例痛风样本、9例正常样本）。

       The study cohort includes 83 Chinese adults. The gout group consists of 35 adult patients who were clinically diagnosed by endocrinologists as gout based on blood uric acids, claim of joint pains and other parameters. The healthy group which serves as control consists of 33 healthy adults. An additional, 15-member group for model validation purpose consists of 6 gout patients and 9 healthy individuals.

测序策略：

      83例样本全部进行16s测序，分析组（16例痛风样本、18例正常样本）和验证组（5例样本）进行metagenome测序。

      For each of the collectively 83 subjects, organismal structure of intestinal microbiota was analyzed by sequencing 16S rRNA gene amplicons. To characterize the functional profiles of microbiota, 16 from the gout group, 18 from the healthy group and 5 from the validation group were randomly selected for whole-metagenome shotgun sequencing.

研究结果：

     1）尿酸、微生物在痛风和正常人群中存在差异

   2）基于metagenome发现痛风、正常样本中富集的MGS（metagenomic species），19个MGS在痛风样本中富集，22个MGS在正常样本中富集

   3）基于16s数据发现痛风和正常人群存在17种差异菌

   4）利用17种菌构建的变量MIG可以很好的区分痛风和正常人群，

研究结论：

      1）利用肠道微生物的差异可以较为理想区分痛风和正常人群；

      2）其中的原理1在于：which revealed that the gout patients were enriched in the metabolism of purine, starch and sucrose, sphingolipid, alanine, aspartate and glutamate, retinol, porphyrin and chlorophyll. On the pathway of purine metabolism, the xanthine dehydrogenase which can degrade the purine to uric acid was enriched in the gout patients, whereas the allantoinase that degrades the uric acid to urea was depleted.

     3）其中的原理2在于：In the network of MGS, Bacteroides caccae (n = 7) and Bacteroides xylanisolvens (n = 4) were enriched in gout patients. In past studies, Bacteroides caccae was recognized one biomarker of IBD.  Significant depletion of Faecalibacterium prausnitzii which was reported to have anti-inflammatory properties and contribute to gut health through butyrate production was observed for gout patients, potentially explaining the decline in butyric acid biosynthesis in gout patients.

文章带来的思考：

     1）借鉴此文的研究思路应用到其他的疾病上，从实验的设计、数据的分析解读及机理探析都做了详细的工作；

     2）商业上的应用想法1，基于此文的一些结果，尝试设计益生菌调节剂调节痛风人群的肠道微生物以改善症状；

     3）商业上的应用想法2，基于此文的一些结果，在疾病诊断上建立联合肠道微生物、血尿酸进行痛风早期诊断的标准；或者单独基于肠道微生物，开发早筛或早诊试剂盒。