Gut microorganisms are vital for many aspects of human health, and the commensal bacterium Akkermansia muciniphila has repeatedly been identified as a key component of intestinal microbiota. Reductions in A. muciniphila abundance are associated with increased prevalence of metabolic disorders such as obesity and type 2 diabetes. It was recently discovered that administration of A. muciniphila has beneficial effects and that these are not diminished, but rather enhanced after pasteurization. Pasteurized A. muciniphila is proposed for use as a food ingredient, and was therefore subjected to a nonclinical safety assessment, comprising genotoxicity assays (bacterial reverse mutation and in vitro mammalian cell micronucleus tests) and a 90‐day toxicity study. For the latter, Han Wistar rats were administered with the vehicle or pasteurized A. muciniphila at doses of 75, 375 or 1500 mg/kg body weight/day (equivalent to 4.8 × 10⁹, 2.4 × 10¹⁰, or 9.6 × 10¹⁰ A. muciniphila cells/kg body weight/day) by oral gavage for 90 consecutive days. The study assessed potential effects on clinical observations (including detailed arena observations and a modified Irwin test), body weight, food and water consumption, clinical pathology, organ weights, and macroscopic and microscopic pathology. The results of both in vitro genotoxicity studies were negative. No test item‐related adverse effects were observed in the 90‐day study; therefore, 1500 mg/kg body weight/day (the highest dose tested, equivalent to 9.6 × 10¹⁰ A. muciniphila cells/kg body weight/day) was established as the no‐observed‐adverse‐effect‐level. These results support that pasteurized A. muciniphila is safe for use as a food ingredient.

中文翻译：

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巴氏杀菌 Akkermansia muciniphila 的毒理学安全性评价。

肠道微生物对人类健康的许多方面都至关重要，共生细菌Akkermansia muciniphila一再被确定为肠道微生物群的关键组成部分。A. muciniphila丰度的减少与代谢紊乱（如肥胖和 2 型糖尿病）的患病率增加有关。最近发现，施用A. muciniphila具有有益效果，并且在巴氏杀菌后这些效果并没有减弱，而是增强。巴氏杀菌A. muciniphila拟用作食品成分，因此进行了非临床安全评估，包括基因毒性试验（细菌回复突变和体外哺乳动物细胞微核试验）和 90 天毒性研究。对于后者，Han Wistar 大鼠以75、375或 1500 mg/kg 体重/天的剂量（相当于 4.8 × 10 ⁹、2.4 × 10 ¹⁰或 9.6 × 10 ¹⁰ A. muciniphila细胞/公斤体重/天），连续 90 天经口强饲。该研究评估了对临床观察（包括详细的竞技场观察和改良的 Irwin 测试）、体重、食物和水消耗、临床病理、器官重量以及宏观和微观病理的潜在影响。两项体外遗传毒性研究的结果均为阴性。在为期 90 天的研究中未观察到与测试项目相关的不良反应；因此，1500 mg/kg 体重/天（测试的最高剂量，相当于 9.6 × 10 ¹⁰ A. muciniphila细胞/kg 体重/天）被确定为未观察到的不良反应水平。这些结果支持巴氏杀菌的A. muciniphila可安全用作食品成分。