Evaluating the safety of probiotic microorganisms is an important part of the development of probiotic products. In this study, we have performed a systematic safety assessment of Limosilactobacillus reuteri ATCC PTA 4659 based on genome analysis, antibiotic susceptibility testing, phenotypic characterization, and a human clinical safety study. Genome sequence analysis showed that the strain is free from virulence and antibiotic resistance genes. Connected to this, phenotypic characterization showed that the strain is susceptible to the main classes of antibiotics. L. reuteri ATCC PTA 4659 was shown to produce histamine, which has previously been described as an anti-inflammatory mediator produced by certain L. reuteri strains. However, the amount of histamine, a biogenic amine, poses no safety concern of a potential product. The strain was investigated in a human clinical safety study and was shown to survive passage through the gastrointestinal tract, both when administered at high (1 × 1011 CFU/day) and low doses (1 × 109 CFU/day). The clinical safety evaluation showed that the doses administered are safe for human consumption. Furthermore, carbohydrate utilization, mucus adhesion and tolerance to acid and bile was studied. It was shown that L. reuteri ATCC PTA 4659 has a very high adhesion to mucus and tolerance to both gastric pH and bile, all potentially important properties for a probiotic strain. Altogether, this study has demonstrated that Limosilactobacillus reuteri ATCC PTA 4659 is safe for human consumption and along with its phenotypic characteristics and previously described anti-inflammatory effects, makes it a promising strain for future probiotic development. NCT01033539

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罗伊氏柠檬酸杆菌 ATCC PTA 4659 的基因组、表型和临床安全性

评价益生菌微生物的安全性是益生菌产品开发的重要组成部分。在本研究中，我们基于基因组分析、抗生素敏感性测试、表型表征和人类临床安全性研究，对罗伊氏柠檬酸杆菌 ATCC PTA 4659 进行了系统的安全性评估。基因组序列分析表明，该菌株不含毒力和抗生素抗性基因。与此相关的是，表型特征表明该菌株对主要类别的抗生素敏感。罗伊氏乳杆菌 ATCC PTA 4659 显示可产生组胺，此前曾将其描述为某些罗伊氏乳杆菌菌株产生的抗炎介质。然而，组胺（一种生物胺）的含量不会对潜在产品造成安全问题。该菌株在一项人体临床安全性研究中进行了调查，结果显示，无论是高剂量（1 × 1011 CFU/天）还是低剂量（1 × 109 CFU/天），该菌株都能在通过胃肠道时存活。临床安全性评价表明，所施用的剂量对于人类食用是安全的。此外，还研究了碳水化合物的利用、粘液粘附以及对酸和胆汁的耐受性。结果表明，罗伊氏乳杆菌 ATCC PTA 4659 对粘液具有非常高的粘附力，并且对胃 pH 值和胆汁具有耐受性，这些都是益生菌菌株的潜在重要特性。总而言之，这项研究证明罗伊氏柠檬酸杆菌 ATCC PTA 4659 对人类食用是安全的，并且其表型特征和先前描述的抗炎作用使其成为未来益生菌开发的有前途的菌株。NCT01033539