Case Digestive Health Research Institute, Case Western University School of Medicine, Cleveland, OH, USA.
Department of Medicine, Case Western University School of Medicine, Cleveland, OH, USA.
Inflamm Bowel Dis. 2023 Jul 5;29(7):1105-1117. doi: 10.1093/ibd/izac284.
Crohn's disease (CD) represents a significant public health challenge. We identified a combination of beneficial probiotic strains (Saccharomyces boulardii, Lactobacillus rhamnosus, Lactobacillus acidophilus, and Bifidobacterium breve) and amylase that may antagonize elevated bacterial pathogens in the inflamed gut. Our aim was to characterize the effect(s) of this novel probiotic supplement in SAMP1/YitFc (SAMP) mice with CD-like ileitis.
Three groups of 7-week-old SAMP mice were used in this study. The first experimental group was administered 1 dose of the probiotic supplement (probiotic strains + amylase) diluted in sterile phosphate-buffered saline (PBS) (0.25 mg in 100 µL of PBS) every day for 56 days through the gavage technique, the second group had a probiotic supplement (probiotic strains without amylase), and the third group was a control group in which animals were administered sterile PBS. At the end of the treatment, mice were sacrificed and ilea were collected for histological scoring of ileitis and NanoString analysis. Stool samples were evaluated by 16S ribosomal RNA and gas chromatography-mass spectrometry analyses.
Histology scores showed that mice treated with probiotics + amylase had a significant decrease of ileitis severity compared with the other 2 groups. 16S ribosomal RNA and gas chromatography-mass spectrometry analysis showed that abundance of species belonging to genus Lachnoclostridium and Mucispirillum schaedleri were significantly increased compared with the other 2 groups, and this increase was associated with augmented production of short-chain fatty acids. NanoString data showed that 21 genes involved in B memory cell development and T cell infiltration were significantly upregulated in probiotic-treated mice and that 3 genes were significantly downregulated.
Our data provide experimental proof for a beneficial effect of the designed probiotic formulation on the severity of CD-like ileitis in the SAMP mouse model, involving both alteration of intestinal genetic pathways and microbial rearrangements. Thus, we propose that this novel probiotic mixture should be further tested as an adjuvant therapy in the treatment of biofilm-associated disorders such as CD, in which it has been proven that polymicrobial imbalance plays a critical role in dysbiosis and gut inflammation.
克罗恩病（CD）是一个重大的公共卫生挑战。我们发现了一组有益的益生菌菌株（布拉氏酵母菌、鼠李糖乳杆菌、嗜酸乳杆菌和短双歧杆菌）和淀粉酶，它们可能拮抗在炎症肠道中升高的细菌病原体。我们的目的是研究这种新型益生菌补充剂对具有 CD 样回肠炎的 SAMP1/YitFc（SAMP）小鼠的影响。
本研究使用了三组 7 周龄的 SAMP 小鼠。第一实验组通过灌胃技术每天给予 1 次益生菌补充剂（益生菌菌株+淀粉酶）稀释于无菌磷酸盐缓冲液（PBS）（100μL PBS 中 0.25mg），持续 56 天；第二组给予益生菌补充剂（无淀粉酶的益生菌菌株）；第三组为对照组，给予无菌 PBS。治疗结束时，处死小鼠并收集回肠进行回肠炎组织学评分和 NanoString 分析。通过 16S 核糖体 RNA 和气相色谱-质谱分析评估粪便样本。
组织学评分显示，与其他两组相比，给予益生菌+淀粉酶的小鼠回肠炎严重程度显著降低。16S 核糖体 RNA 和气相色谱-质谱分析显示，与其他两组相比，属 Lachnoclostridium 和 Mucispirillum schaedleri 的物种丰度显著增加，这种增加与短链脂肪酸产量的增加有关。NanoString 数据显示，21 个参与 B 记忆细胞发育和 T 细胞浸润的基因在益生菌处理的小鼠中显著上调，而 3 个基因显著下调。
我们的数据为设计的益生菌配方对 SAMP 小鼠模型中 CD 样回肠炎严重程度的有益作用提供了实验证据，这涉及肠道遗传途径和微生物排列的改变。因此，我们建议进一步测试这种新型益生菌混合物作为生物膜相关疾病（如 CD）的辅助治疗，其中已经证明多微生物失衡在肠道炎症中的失调和肠道炎症中起着关键作用。
