Limosilactobacillus reuteri and Lacticaseibacillus rhamnosus GG differentially affect gut microbes and metabolites in mice with Treg deficiency.
Limosilactobacillus reuteri and Lacticaseibacillus rhamnosus GG differentially affect gut microbes and metabolites in mice with Treg deficiency.
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罗伊氏柠檬酸乳杆菌和鼠李糖乳杆菌 GG 对 Treg 缺陷小鼠的肠道微生物和代谢物产生不同的影响。
DOI：
10.1152/ajpgi.00072.2021
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Rhoads,JMarc
中科院分区：
文献类型：
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作者：
Liu,Yuying;Hoang,ThomasK;Taylor,ChristopherM;Park,EvelynS;Freeborn,Jasmin;Luo,Meng;Roos,Stefan;Rhoads,JMarc
Treg缺陷会在人类和这种疾病的小鼠模型scurfy(SF)小鼠中导致一种称为IPEX综合征的致命的、由CD4+T细胞驱动的自身免疫性疾病(免疫失调、多内分泌疾病和肠病，具有X连锁遗传)。给SF小鼠饲喂利莫硅乳杆菌DSM 17938(LR 17938，LR)可重新编程肠道微生物区系，减缓疾病进展，延长寿命。然而，与其他益生菌相比，LR产生这些作用的有效性和机制尚不清楚。我们将LR与广泛研究的益生菌Lacticaseibacillusrhamnosus GG(LGG)进行了比较。在延长生存期方面，LR比LGG更有效。两种益生菌都恢复了粪便微生物α多样性，但它们产生了不同的粪便细菌群和不同调节的微生物相对丰度(RA)。而LR则使拟杆菌门、拟杆菌属和副拟杆菌门的RA增加，从而逆转了SF表型的变化。LGG主要降低类杆菌属的RA。LR和LGG均能降低潜在致病分类群_γ-变形杆菌。血浆代谢组学显示696种代谢物之间存在显著差异。我们在SF小鼠中观察到与LR或LGG治疗相关的许多代谢物簇的相似变化。然而，LR的一个独特的作用是增加了血浆腺苷代谢产物的丰度，如肌苷，我们之前已经证明了它具有免疫调节作用。综上所述：1)不同的益生菌在Treg缺乏症小鼠的粪便微生物群落中产生了不同的特征；2)当比较不同的益生菌时，有不同菌株特有的微生物产品具有不同的抗炎特性，强化了在治疗自身免疫性疾病时“一刀切”的概念。在治疗Treg缺乏诱导的自身免疫方面，reuriLimosiltobacillusreuriDSM 17938(LR)显示出比LGG更有效的效果。研究表明，两种不同的益生菌在Treg缺陷小鼠的粪便微生物群落中产生了不同的特征，但总体上在全球血浆代谢物中有许多相似之处。然而，有不同菌株特定的微生物产品具有不同的抗炎特性，这强化了在治疗自身免疫性疾病时“一刀切不适合所有人”的概念。
Treg deficiency causes a lethal, CD4+T cell-driven autoimmune disease called IPEX syndrome (immunodysregulation, polyendocrinopathy, and enteropathy, with X-linked inheritance) in humans and in the scurfy (SF) mouse, a mouse model of the disease. FeedingLimosilactobacillus reuteriDSM 17938 (LR 17938, LR) to SF mice reprograms the gut microbiota, reduces disease progression, and prolongs lifespan. However, the efficacy and mechanism of LR, compared with other probiotics, in producing these effects is unknown. We compared LR withLacticaseibacillus rhamnosus GG(LGG), an extensively investigated probiotic. LR was more effective than LGG in prolonging survival. Both probiotics restored the fecal microbial alpha diversity, but they produced distinct fecal bacterial clusters and differentially modulated microbial relative abundance (RA). LR increased the RA of phylum_Firmicutes,genus_Oscillospirawhereas LR reduced phylum_Bacteroidetes,genus_Bacteroidesandgenus_Parabacteroides, reversing changes attributed to the SF phenotype. LGG primarily reduced the RA ofgenus_Bacteroides. Both LR and LGG reduced the potentially pathogenic taxonclass_γ-proteobacteria. Plasma metabolomics revealed substantial differences among 696 metabolites. We observed similar changes of many clusters of metabolites in SF mice associated with treatment with either LR or LGG. However, a unique effect of LR was to increase the abundance of plasma adenosine metabolites such as inosine, which we previously showed had immune modulatory effects. In conclusion:1) different probiotics produce distinct signatures in the fecal microbial community in mice with Treg deficiency; and2) when comparing different probiotics, there are strain-specific microbial products with different anti-inflammatory properties, reinforcing the concept that “one size does not fit all” in the treatment of autoimmune disease.NEW & NOTEWORTHYIn the treatment of Treg-deficiency-induced autoimmunity,Limosilactobacillus reuteriDSM 17938 (LR) showed greater efficacy thanLacticaseibacillus rhamnosus GG(LGG). The study demonstrated that two different probiotics produce distinct signatures in the fecal microbial community in mice with Treg deficiency, but with many similarities in global plasma metabolites in general. However, there are strain-specific microbial products with different anti-inflammatory properties, reinforcing the concept that “one size does not fit all” in the treatment of autoimmune disease.