Raw numerical data.

Protozoa in the genus Cryptosporidium infect intestinal epithelial cells. The profile of the fecal microbiota has been shown to impact the proliferation of Cryptosporidium parvum in a mouse model of cryptosporidiosis and a reverse effect of the parasite on the microbiota has also been described. The mechanisms underlying this interaction are unknown. The lack of effective drugs and vaccines is motivating the search for pro- or prebiotics capable of increasing resistance to parasite proliferation in the gastrointestinal tract. To understand if and how the intestinal microbiota could be harnessed for this purpose, we tested if C. parvum proliferation in the mouse responds to oral administration of Escherichia coli. This bacterium was chosen because of its reported importance in mediating colonization resistance, because it encodes tryptophanase, an enzyme which converts tryptophan into indole, and because of the availability of an ampicillin-resistant strain expressing green fluorescent protein. Excretion of GFP+ E. coli in the feces was highly variable among mice, a phenomenon which is also observed with C. parvum. A positive correlation between fecal output of probiotic E. coli and C. parvum was observed. This finding may indicate that intestinal colonization with two microorganisms as different as E. coli and C. parvum responds to the same conditions in the GI tract. Consistent with an effect of the microbiota on cryptosporidiosis, the pre-infection microbiota taxonomic profile was predictive of mouse susceptibility to C. parvum. Contrary to the reported inhibitory effect of indole on C. parvum, microbiota indole production potential was positively correlated with C. parvum fecal output. The effect of cryptosporidiosis on the microbiota was characterized by an expansion of facultative anaerobes, particularly Gammaproteobacteria. This study is a first attempt to assess the proliferation in the mouse of a defined probiotic and quantify its effect on C. parvum development.

隐孢子虫属（Cryptosporidium）的原生动物可侵染肠道上皮细胞。已有研究证实，粪便微生物群的组成特征会影响隐孢子虫病小鼠模型中微小隐孢子虫（Cryptosporidium parvum）的增殖，且该寄生虫对微生物群的反向调控作用亦有报道。二者互作的具体分子机制目前仍不明晰。由于当前缺乏有效的治疗药物与疫苗，学界正致力于筛选可提升胃肠道抗寄生虫增殖能力的益生菌（probiotics）与益生元（prebiotics）。为探明肠道微生物群是否可被用于该防控目标，以及具体作用路径，本研究探究了小鼠体内微小隐孢子虫的增殖是否会受口服大肠杆菌（Escherichia coli）干预的影响。选择该菌株的原因如下：其一，已有研究证实其在介导定植抗性中发挥关键作用；其二，该菌编码色氨酸酶（tryptophanase）——一种可将色氨酸转化为吲哚（indole）的酶；其三，目前已有携带绿色荧光蛋白（green fluorescent protein, GFP）的氨苄青霉素抗性菌株可供使用。小鼠粪便中绿色荧光蛋白标记的大肠杆菌（GFP+ E. coli）的排出量存在显著个体差异，这一现象与微小隐孢子虫的排出情况一致。本研究观察到，益生菌型大肠杆菌的粪便排出量与微小隐孢子虫的粪便排出量呈正相关。该发现提示，大肠杆菌与微小隐孢子虫这两类差异显著的微生物在肠道的定植情况，会响应胃肠道内相同的环境条件。与微生物群对隐孢子虫病的调控效应相符，感染前的微生物群分类学特征可预测小鼠对微小隐孢子虫的易感程度。与此前报道的吲哚对微小隐孢子虫的抑制作用相悖，微生物群的吲哚合成潜力与微小隐孢子虫的粪便排出量呈正相关。隐孢子虫病对微生物群的影响表现为兼性厌氧菌（facultative anaerobes）的丰度扩增，尤以γ-变形菌纲（Gammaproteobacteria）最为显著。本研究首次尝试评估特定益生菌在小鼠体内的增殖情况，并量化其对微小隐孢子虫发育的影响。