Zabolotny Institute of microbiology and virology, National Academy of Sciences of Ukraine, 154, Akad. Zabolotny str, Kyiv, 03143, Ukraine.
Bogomolets National Medical University, 13, T. Shevchenko blvd, Kyiv, 01601, Ukraine.
Probiotics Antimicrob Proteins. 2021 Dec;13(6):1644-1657. doi: 10.1007/s12602-021-09789-1. Epub 2021 Apr 20.
Probiotics, in particular Lactobacillus (lactic acid bacteria, LAB) strains, are widely used in clinical practice. Despite that these probiotics have GRAS (generally regarded as safe) and qualified presumption of safety (QPS) statuses, the safety of particular strains still needs to be thoroughly studied. The aim of the study was to evaluate the safety of Lact. casei IMV B-7280 strain by investigating toxicity and the effects on gut microbiota in experimental animal model. Male BALB/c mice (7-8 weeks, weight 20-24 g) were treated with amounts of Lact. casei IMV B-7280 strain: 5 × 10, 5 × 10, or 5 × 10 CFU/animal once per day during 7 days, or in the amount of 1 × 10 CFU/animal once per day during 3 days (most of the proposed probiotic doses for humans-from 10 to 10 CFU) and monitored during 14 days. Blood tests and serum biochemistry were conducted; the cecal content from mice of the experimental and control groups were freshly collected and analyzed. At the end of the experiments (15th day), the presence of LAB in the heart, liver, kidney, and mesenteric lymph nodes and peripheral blood was determined; histology of the brain, liver, heart, fragments of the small and large intestine, and mesenteric lymph nodes was conducted. Survival rate of BALB/c mice treated with Lact. casei IMV B-7280 strain in different concentrations in toxicity experiments during 14 days was 100%. We observed no signs of toxicity as changes in gait, lethargy, sleep, somatomotor activity as well as changes in fur, eyes, skin and mucous membranes, tremors, behavior pattern, convulsions, salivation, diarrhea, and local injuries in mice from all experimental groups. After administration of probiotic strain, the number of opportunistic bacteria in cecal contents, such as Staphylococcus spp., Candida spp., Pseudomonas spp., and total aerobic and optionally anaerobic bacteria decreased compared to controls; the population of beneficial bacteria such as lactobacilli increased in cecal contents of these mice. LAB were not detected in the peripheral blood, heart, liver, kidneys, and mesenteric lymph nodes after administration of this strain to intact mice. Lact. casei IMV B-7280 strain is safe at dose up to 10 CFU/animal during 3- and 7-day oral administration to mice and has a positive effect on the gut microbiota composition; it could be potentially considered as safe probiotic for humans.
益生菌，尤其是乳杆菌（乳酸菌，LAB）菌株，在临床实践中被广泛应用。尽管这些益生菌具有 GRAS（一般认为安全）和合格的假定安全性（QPS）地位，但特定菌株的安全性仍需要进行彻底研究。本研究的目的是通过在实验动物模型中研究毒性和对肠道微生物群的影响来评估 Lact. casei IMV B-7280 菌株的安全性。雄性 BALB/c 小鼠（7-8 周龄，体重 20-24g）每天接受 5×10、5×10 或 5×10 CFU/动物的 Lact. casei IMV B-7280 菌株剂量，连续 7 天，或每天接受 1×10 CFU/动物的剂量，连续 3 天（大多数拟议的人类益生菌剂量为 10 到 10 CFU），并在 14 天内进行监测。进行血液检查和血清生化检查；新鲜收集实验组和对照组小鼠的盲肠内容物并进行分析。在实验结束时（第 15 天），确定 LAB 在心脏、肝脏、肾脏和肠系膜淋巴结以及外周血中的存在情况；对大脑、肝脏、心脏、小肠和大肠片段以及肠系膜淋巴结进行组织学检查。在 14 天的毒性实验中，用不同浓度的 Lact. casei IMV B-7280 菌株处理的 BALB/c 小鼠的存活率为 100%。我们没有观察到任何毒性迹象，例如步态改变、昏睡、睡眠、躯体运动活动以及小鼠的皮毛、眼睛、皮肤和粘膜、震颤、行为模式、抽搐、流涎、腹泻和局部损伤。在给予益生菌菌株后，盲肠内容物中的机会性细菌数量（如金黄色葡萄球菌、念珠菌、假单胞菌和总需氧和兼性厌氧菌）与对照组相比减少；有益细菌（如乳酸菌）的数量增加。在给完整小鼠施用该菌株后，未在其外周血、心脏、肝脏、肾脏和肠系膜淋巴结中检测到 LAB。Lact. casei IMV B-7280 菌株在 3 至 7 天的口服给予小鼠时，剂量高达 10 CFU/动物，是安全的，并且对肠道微生物群组成有积极影响；它可能被认为是人类安全的益生菌。
