A novel probiotic therapeutic in a murine model of Clostridioides difficile colitis.

A novel probiotic therapeutic in a murine model of Clostridioides difficile colitis.
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DOI:
10.1080/19490976.2020.1814119
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发表时间:
2020-11-09
期刊:
影响因子:
12.2
通讯作者:
Besner GE
Besner GE
中科院分区:
医学2区
文献类型:
--
作者:
Shelby RD;Janzow GE;Mashburn-Warren L;Galley J;Tengberg N;Navarro J;Conces M;Bailey MT;Goodman SD;Besner GE

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艰难梭菌感染(CDI)是抗菌素相关性腹泻的常见原因。益生菌在降低其发病率和严重程度方面显示出不同的结果。我们在小鼠模型中检测了使用一种新型益生菌生物膜递送系统给予罗伊氏乳杆菌治疗和预防CDI的功效。对于预防治疗,小鼠接受口服抗生素鸡尾酒,然后注射克林霉素,然后给予益生菌(浮游与生物膜状态),然后口服艰难梭菌灌胃。对于治疗,小鼠首先接受抗生素和艰难梭菌,然后给予益生菌。评定临床疾病评分(CSS)和肠组织损伤评分(HIS)。在预防性治疗模型中,67%暴露于艰难梭菌的未治疗小鼠的CSS≥6,这与艰难梭菌感染一致(与未暴露小鼠相比p< 0.001)。在浮游Lr处理的小鼠中,55%的小鼠CSS≥6,而在生物膜状态下的Lr处理的小鼠中,只有19%的小鼠CSS≥6 (p< 0.001)。与接受生理盐水的小鼠(p= 0.004676)或接受Lr的小鼠(p= 0.003185)相比,接受Lr + dm -麦芽糖的小鼠体重减轻最少。HIS: 77%暴露于艰难梭菌的未治疗小鼠HIS评分≥4,这与艰难梭菌感染一致。浮游Lr处理的小鼠HIS≥4的比例为62%,而生物膜态Lr处理的小鼠HIS≥4的比例仅为19%。(p <措施)。生物膜态Lr处理小鼠的存活率高于未处理小鼠和浮游Lr处理小鼠(p≤0.05)。治疗组的体重减轻、CSS、HIS和生存率也有类似的结果。单剂量的生物膜状态的罗伊氏乳杆菌作为预防和治疗治疗,可降低实验性艰难梭菌感染的严重程度和发生率。
Clostridioides difficile infection (CDI) is a common cause of antimicrobial-associated diarrhea. Probiotics have shown variable results in decreasing its incidence and severity. We examined the efficacy of Lactobacillus reuteri administered using a novel probiotic biofilm delivery system in the treatment and prevention of CDI in a murine model. For prophylactic therapy, mice received an oral antibiotic cocktail followed by clindamycin injection, followed by probiotic administration (planktonic vs. biofilm state), followed by C. difficile oral gavage. For treatment therapy, mice received antibiotics and C. difficile first, followed by probiotic administration. Clinical sickness scores (CSS) and intestinal histologic injury scores (HIS) were assigned. In the Prophylactic Therapy model, CSS: 67% of untreated mice exposed to C. difficile demonstrated CSS ≥ 6, which is consistent with C. difficile infection (p< .001 compared to unexposed mice). In mice treated with planktonic Lr, 55% had a CSS ≥ 6, but only 19% of mice treated with Lr in its biofilm state had CSS ≥ 6 (p< .001). Mice receiving Lr + DM-Maltose lost the least amount of weight compared to mice receiving saline (p = .004676) or to mice receiving Lr (p= .003185). HIS: 77% of untreated mice exposed to C. difficile had HIS scores ≥4, which is consistent with C. difficile infection. In mice treated with planktonic Lr, 62% had HIS ≥4, but only 19% of mice treated with Lr in its biofilm state had HIS ≥4. (p< .001). Additionally, mice treated with Lr in its biofilm state had better survival compared to untreated mice and to mice treated with planktonic Lr (p ≤ 0.05). Similar findings for weight loss, CSS, HIS and survival were obtained for Treatment Therapy. A single dose of Lactobacillus reuteri in its biofilm state reduces the severity and incidence of experimental C. difficile infection when administered as both prophylactic and treatment therapy.
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