Dziarski Roman, Park Shin Yong, Kashyap Des Raj, Dowd Scot E, Gupta Dipika
Indiana University School of Medicine-Northwest, Gary, Indiana, United States of America.
MR DNA Molecular Research LP, Shallowater, Texas, United States of America.
PLoS One. 2016 Jan 4;11(1):e0146162. doi: 10.1371/journal.pone.0146162. eCollection 2016.
Dysbiosis is a hallmark of inflammatory bowel disease (IBD), but it is unclear which specific intestinal bacteria predispose to and which protect from IBD and how they are regulated. Peptidoglycan recognition proteins (Pglyrps) are antibacterial, participate in maintaining intestinal microflora, and modulate inflammatory responses. Mice deficient in any one of the four Pglyrp genes are more sensitive to dextran sulfate sodium (DSS)-induced colitis, and stools from Pglyrp-deficient mice transferred to wild type (WT) germ-free mice predispose them to much more severe colitis than stools from WT mice. However, the identities of these Pglyrp-regulated bacteria that predispose Pglyrp-deficient mice to colitis or protect WT mice from colitis are not known. Here we identified significant changes in β-diversity of stool bacteria in Pglyrp-deficient mice compared with WT mice. The most consistent changes in microbiome in all Pglyrp-deficient mice were in Bacteroidales, from which we selected four species, two with increased abundance (Prevotella falsenii and Parabacteroides distasonis) and two with decreased abundance (Bacteroides eggerthii and Alistipes finegoldii). We then gavaged WT mice with stock type strains of these species to test the hypothesis that they predispose to or protect from DSS-induced colitis. P. falsenii, P. distasonis, and B. eggerthii all enhanced DSS-induced colitis in both WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora. By contrast, A. finegoldii (which is the most abundant species in WT mice) attenuated DSS-induced colitis both in WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora, similar to the colitis protective effect of the entire normal microflora. These results identify P. falsenii, P. distasonis, and B. eggerthii as colitis-promoting species and A. finegoldii as colitis-protective species.
菌群失调是炎症性肠病（IBD）的一个标志，但尚不清楚哪些特定的肠道细菌易引发IBD以及哪些细菌可预防IBD，也不清楚它们是如何被调节的。肽聚糖识别蛋白（Pglyrps）具有抗菌作用，参与维持肠道微生物群，并调节炎症反应。缺乏四种Pglyrp基因中任何一种的小鼠对葡聚糖硫酸钠（DSS）诱导的结肠炎更敏感，将Pglyrp基因缺陷小鼠的粪便转移到野生型（WT）无菌小鼠中，相比于WT小鼠的粪便，前者会使受体小鼠更容易患上更严重的结肠炎。然而，这些使Pglyrp基因缺陷小鼠易患结肠炎或保护WT小鼠免受结肠炎的Pglyrp调节细菌的具体种类尚不清楚。在这里，我们发现与WT小鼠相比，Pglyrp基因缺陷小鼠粪便细菌的β多样性有显著变化。所有Pglyrp基因缺陷小鼠中，微生物群最一致的变化发生在拟杆菌目，我们从该目中选择了四个物种，其中两个丰度增加（假普雷沃菌和狄氏副拟杆菌），两个丰度降低（埃氏拟杆菌和费氏艾利斯菌）。然后，我们用这些物种的标准菌株灌胃WT小鼠，以验证它们易引发或预防DSS诱导结肠炎的假说。假普雷沃菌、狄氏副拟杆菌和埃氏拟杆菌在肠道微生物群未受干扰的WT小鼠以及肠道微生物群因抗生素而减少的WT小鼠中，均增强了DSS诱导的结肠炎。相比之下，费氏艾利斯菌（WT小鼠中最丰富的物种）在肠道微生物群未受干扰的WT小鼠以及肠道微生物群因抗生素而减少的WT小鼠中，均减轻了DSS诱导的结肠炎，类似于整个正常微生物群的结肠炎保护作用。这些结果确定假普雷沃菌、狄氏副拟杆菌和埃氏拟杆菌为促结肠炎物种，而费氏艾利斯菌为抗结肠炎物种。
