Latar Belakang: Mukositis rongga mulut merupakan efek samping pada anti kanker 5-fluorourasil (5-FU). Kemoterapi memicu disbiosis yang berkorelasi dengan keparahan mukositis. Penggunaan probiotik merupakan pendekatan baru untuk mengurangi keparahan mukositis. Tujuan: mengetahui efek Lactococcus lactis subsp. lactis strain Y-PDH terhadap keparahan lesi dan modulasi mikrobiota terkait mukositis rongga mulut. Metode: Sebanyak 48 tikus Sprague Dawley dibagi menjadi enam kelompok: normal (N), normal dan L. lactis subsp. lactis strain Y-PDH dosis tinggi (N + LL HD), kelompok induksi 5-FU (5FU), induksi 5-FU dan diberikan LL LD (5FU + LL LD), induksi 5-FU dan diberikan LL HD (5FU + LL HD), serta induksi 5-FU dan diberikan L. reuteri DSM 17983 (5FU + LR). Pada hari ke sepuluh dilakukan penilaian keparahan klinis, biopsi mukosa bukal tikus untuk penilaian histopatologi, penilaian mediator inflamasi TNFα, IL-6, dan IL-10 dengan ELISA, penanda FGF7 dan MMP2 dengan imunohistokimia, dan swab mukosa mulut untuk analisis metagenomik. Hasil: Pemberian LL LD menurunkan keparahan klinis dan histopatologis pada kelompok yang diinduksi 5-FU. Terjadi penurunan TNFα, IL-6, dan IL-10, penurunan ekspresi FGF7 dan peningkatan ekspresi MMP2. Pemberian LL LD menurunkan kelimpahan genus Fusobacterium, meningkatkan kelimpahan Rothia, serta meningkatkan richness dan evenness pada kelompok 5-FU. Namun, pemberian LL HD meningkatkan keparahan klinis dan mengubah komposisi bakteri secara signifikan. Kesimpulan: Pemberian LL LD mengurangi keparahan lesi mukositis rongga mulut yang diinduksi 5-FU secara klinis dan histopatologis. Perbaikan oleh LL LD disertai penurunan kadar sitokin inflamasi, modulasi penanda penyembuhan serta restorasi disbiosis.

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Background: Oral mucositis is one of the most common side effects in anti-cance 5-fluorouracil (5-FU). Mucositis disrupt nutrition intake and interrupt anti-cancer regimens. The severity of oral mucositis correlates with dysbiosis The use of probiotics becomes a novel potential therapy to reduce mucositis severity by restoring dysbiosis. Objective: To evaluate the effect of L. lactis subsp. lactis strain Y-PDH on lesion severity and microbiota modulation in oral mucositis. Methods: We randomly divided 48 Sprague-Dawley into six groups: normal (N), normal and high dose L. lactis subsp. lactis strain Y-PDH (N + LL HD), 5-FU-induced mucositis i.p. (5FU), 5-FU induced and LL LD (5FU + LL LD), 5-FU induced and LL HD (5FU + LL HD), and L. reuteri DSM 17983 (5FU + LR). On the tenth day, we observed clinical severity, and took buccal mucosa biopsy for histopathology analysis, TNFα, IL-6, and IL-10 quantifications, wound healing markers (FGF7 and MMP2) evaluation with immunohistochemistry and oral mucosal swab for metagenomic analysis. Result: LL LD reduce clinical and histopathological severity in 5-FU-induced groups. There were decrease in TNFα, IL-6, and IL-10. The expression of FGF7 was diminished and the expression of MMP2 was increased. LL LD lower the abundance of Fusobacterium, increase the abundance of Rothia, and increase the richness and evenness of 5-FU groups. In contrast, LL HD increased clinical severity and significantly changed the bacterial composition Conclusion: Administration of LL LD can reduce clinical and histopathological severity in 5-FU induced oral mucositis. The improvement was concurrent with the decrease of inflammatory level, modulation of wound healing marker and restoration of dysbiosis.