微生物群能夠通過調節免疫系統、代謝營養物質和抵禦包括細菌和病毒在內的病原體， 在維持人類健康方面發揮著至關重要的作用。 微生物群失調或失衡與多種疾病有關， 表明了微生物群與人類健康之間相互作用的重要性。 在本研究中，我們首先研究液化 澱粉芽孢桿菌(Bacillus amyloliquefacien, B. amyloliquefaciens)對發芽水稻種子 γ-胺基丁酸 (Gamma-aminobutyric acid, GABA) 積累的影響，從而增加小鼠背部皮膚中的 I 型膠原 蛋白 (type I collagen, COL1)。不管有沒有液化澱粉芽孢桿菌對發芽水稻進行孵育，都能 從中檢測到 GABA 含量，並且使用蛋白質轉漬法能夠檢測到大量的 COL1。結果表明， 局部應用與液化澱粉芽孢桿菌共培養水稻種子的上清液可以顯著增加小鼠皮膚中 COL1 的產生。其次，我們研究了痤瘡丙酸桿菌(Cutibacterium acnes, C. acnes)的脂肪酶 或棕櫚酸是否可以促進小鼠產生針對 SARS-CoV-2 膜蛋白（ membrane glycoprotein M） 的抗體。每隔 2 周使用膜蛋白加上脂肪酶或棕櫚酸對小鼠進行 3 次皮下免疫注射。並通 過酵素連結免疫吸附分析法(Enzyme Linked Immune Sorbent Assay, ELISA) 對小鼠肺部 中的白細胞介素-6(level interleukin-6, IL-6)水平進行定量。我們的數據表明，與小鼠單獨 使用膜蛋白的免疫相比，使用膜蛋白加脂肪酶或棕櫚酸的聯合免疫有效誘導了高抗體反 應。此外，在使用膜蛋白加脂肪酶或棕櫚酸免疫的小鼠肺中，由 SARS-CoV-2 膜蛋白誘 導產生的 IL-6 顯著減少。總而言之，這些研究提供了對天然來源的佐劑在 COVID-19 疫苗開發中的潛力以及微生物群中細菌作為治療人類疾病的生物療法的重要性的見解。;The microbiome has been shown to play a crucial role in maintaining human health by regulating the immune system, metabolizing nutrients, and protecting against pathogens including bacteria and viruses. Dysbiosis or imbalance in the microbiome has been linked to various diseases, highlighting the importance of understanding the interaction between microbiome and human health. First, we investigated the effect of Bacillus amyloliquefaciens (B. amyloliquefaciens) on the accumulation of gamma-aminobutyric acid (GABA) in germinated rice seed. Afterward, we tested the effect of those germinated rice seed on production of type I collagen (COL1) in the dorsal skin of mice. GABA content were detected in the germinated rice incubated with or without B. amyloliquefaciens by the colorimetric test. Further, amount of COL1 were detected using western blot method. The results showed that the topical application of supernatant from rice seed co-cultivated with B. amyloliquefaciens can significantly increase the production of COL1 in the dorsal skin of mice. Secondly, we investigated whether Cutibacterium acnes (C. acnes) lipase or palmitic acid could boost the antibody production against SARS-CoV-2 membrane glycoprotein (M protein) in mice. Mice were subcutaneously immunized with M protein plus lipase or palmitic acid 3 times in 2-week intervals. The level interleukin (IL)-6 in the lung of mice were quantified by enzyme linked immune sorbent assay (ELISA). Our data demonstrated that co-immunization with M protein plus lipase or palmitic acid effectively induced a high antibody response in comparison to immunization with M protein alone in mice. Furthermore, the production of IL-6 induced by SARS-CoV-2 M protein was drastically reduced in the lung of mice immunized with M protein plus lipase or palmitic acid. In summary, these studies provide insights into the potential of naturally derived adjuvants for COVID-19 vaccine development and the importance of bacteria in the microbiome as biotherapeutics for treatments of human diseases.
