困難梭狀芽孢桿菌是一種人類胃腸道致病菌，並且被認為是造成醫院和社區環境中感染性腹瀉的主要原因，隨著困難梭狀芽孢桿菌感染症發病率、死亡率和復發率的嚴重上升，此公共衛生威脅必須進行研究和發展出有效的治療方式。然而，傳統的臨床治療仍依賴使用廣效型抗生素如萬古黴素和甲硝唑，此治療方式常導致疾病復發以及多重抗藥性菌株的演化出現，先前發表的報告已證明源自天然植物中的中碳鏈脂肪酸可以在體外實驗抑制多種人類致病菌的細菌生長，因此我們假設這些中碳鏈脂肪酸也可能對困難梭狀芽孢桿菌具有高潛力的抑制效果。在本篇研究中，我們目標在鑒定新型天然抑制劑用於困難梭狀芽孢桿菌感染症的輔助治療，在體外實驗中我們證實月桂酸對於多種困難梭狀芽孢桿菌之分離菌株的抗菌特性，且月桂酸會明顯地干擾細菌生物膜的形成和破壞已建立好的生物膜。有趣的是，在牛磺膽酸存在下月桂酸能夠降低萌芽時孢子的生長，此外我們進一步研究月桂酸的抑菌機制是由於損害細菌細胞膜和產生活性氧化物質，並在體內小鼠感染模型實驗中評估月桂酸的治療成效。總結而言，我們論斷月桂酸此天然存在的中碳鏈脂肪酸是一個新穎的困難梭狀芽孢桿菌抑制劑，可以作為一個替代療法用以降低困難梭狀芽孢桿菌感染症的症狀。

Clostridium difficile (C. difficile) is a human gastrointestinal pathogen and considered to be the leading cause of infectious diarrhea in hospital and community surroundings. With the severely increasing morbidity, mortality and recurrence of C. difficile infection (CDI), this public health threat must be undertaken to research and develop effective treatments for clinical application. However, traditional clinical treatment relies on broad-spectrum antibiotic usage such as vancomycin and metronidazole which can often result in relapses and the emergence of multiple resistant strains. Previous published reports have demonstrated that natural plant derived medium chain fatty acids (MCFAs) can inhibit the bacterial growth of multiple human pathogens in vitro. Consequently, we hypothesized that these MCFAs might also present a high potential inhibitory effect against C. difficile. In this study, we aimed to identify novel natural inhibitors of C. difficile which could be used as adjunct treatment for CDI. In our in vitro works, we confirmed the antibacterial property of lauric acid against multiple toxigenic C. difficile isolates. Biofilm formation and established biofilm were also significantly reduced by the addition of lauric acid in a dose-dependent manner. Interestingly, lauric acid was able to decrease spore outgrowth during germination in the presence of taurocholic acid. In addition, we further investigated the mechanisms of lauric acid were owing to damage bacterial cell membrane and generate reactive oxygen species (ROS) products. The therapeutic efficacy of lauric acid was also evaluated in vivo using a murine model of infection. Taken together, we concluded that lauric acid, naturally occurring MCFA, is a novel C. difficile inhibitor which could be used as an alternative treatment to lower the symptoms of CDI.

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