Fecal Indole as a Biomarker of Susceptibility to Cryptosporidium Infection
Fecal Indole as a Biomarker of Susceptibility to Cryptosporidium Infection
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DOI：
10.1128/iai.00336-16
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发表时间：
2016-08-01
影响因子：
3.1
通讯作者：
Hixson, James
中科院分区：
文献类型：
--
作者：
Chappell, Cynthia L.;Darkoh, Charles;Hixson, James
隐孢子虫在世界范围内引起严重的腹泻，特别是在儿童和免疫功能低下的个体中，目前没有有效的药物治疗可用于那些最需要它的人。在本报告中，先前的志愿者感染性研究已经扩展到检查粪便吲哚和吲哚产生（IP）肠道微生物群与隐孢子虫感染结果之间的关系。对50名受试者和19个常见肠道微生物群的粪便中吲哚浓度（FICs）进行了测定，其中包括6个IP分类群（11名受试者）。在基线时，攻击后感染的患者的平均FIC（+/-标准差）为1.66 +/- 0.80 mM，而未感染的患者为3.20 +/- 1.23 mM （P = 0.0001）。只有11.1%的FIC为> 2.5 mM的受试者在攻击后感染，而FIC < 2.5 mM的受试者中感染的比例为65.2%。相反，感染受试者在基线或腹泻期间的FIC与感染强度或疾病严重程度无关。在基线FIC为> 2.5 mM的志愿者中，大肠杆菌、芽孢杆菌和梭状芽孢杆菌的相对丰度（百分比）要高出>= 2.5倍，而在基线FIC < 2.5 mM的志愿者中，化脓性拟杆菌、脆弱芽孢杆菌和嗜粘液阿克曼氏菌的相对丰度（百分比）要高得多。这些数据表明，一些IP细菌，或者可能仅吲哚，可以影响隐孢子虫建立感染的能力。因此，肠道中预先存在的吲哚水平与卵囊剂量和免疫状态一起成为决定隐孢子虫暴露结果的重要因素。
Cryptosporidium causes significant diarrhea worldwide, especially among children and immunocompromised individuals, and no effective drug treatment is currently available for those who need it most. In this report, previous volunteer infectivity studies have been extended to examine the association between fecal indole and indole-producing (IP) gut microbiota on the outcome of a Cryptosporidium infection. Fecal indole concentrations (FICs) of 50 subjects and 19 taxa of common gut microbiota, including six IP taxa (11 subjects) were determined in stool samples collected before and after a challenge with Cryptosporidium oocysts. At the baseline, the mean FIC (+/- the standard deviation) was 1.66 +/- 0.80 mM in those who became infected after a challenge versus 3.20 +/- 1.23 mM in those who remained uninfected (P = 0.0001). Only 11.1% of the subjects with a FIC of > 2.5 mM became infected after a challenge versus 65.2% of the subjects with a FIC of < 2.5 mM. In contrast, the FICs of infected subjects at the baseline or during diarrhea were not correlated with infection intensity or disease severity. The relative abundances (percent) of Escherichia coli, Bacillus spp., and Clostridium spp. were greater >= 2.5-fold in volunteers with a baseline FIC of> 2.5 mM, while those of Bacteroides pyogenes, B. fragilis, and Akkermansia muciniphila were greater in those with a baseline FIC of < 2.5 mM. These data indicate that some IP bacteria, or perhaps indole alone, can influence the ability of Cryptosporidium to establish an infection. Thus, preexisting indole levels in the gut join the oocyst dose and immune status as important factors that determine the outcome of Cryptosporidium exposure.