Electronic Theses and Dissertation

Abstrak

HUBUNGAN KOMPOSISI DAN KERAGAMAN
MIKROBIOTA USUS DENGAN TAMPILAN KLINIS
PENYAKIT GRAVES

Latar Belakang: Penyakit graves adalah penyakit autoimun tiroid yang umum, namun patogenesisnya belum sepenuhnya dipahami. Bukti ilmiah terbaru menunjukkan adanya peran disbiosis mikrobiota usus dalam perkembangan dan progresivitas penyakit autoimun. Penelitian ini bertujuan untuk mengetahui hubungan antara tampilan klinis penyakit graves dengan komposisi dan keragaman mikrobiota usus.
Metode: Penelitian ini merupakan studi observasional dengan desain case-control yang dilakukan di RSUD dr. Zainoel Abidin Banda Aceh. Total 48 subjek berpartisipasi, terdiri dari 24 pasien penyakit graves yang baru terdiagnosis dan belum mendapat terapi (treatment-naïve) sebagai kelompok kasus, dan 24 individu sehat sebagai kelompok kontrol. Data klinis berupa indeks wayne, GO, dan derajat goiter dicatat dalam penelitian. Analisis mikrobiota usus dari sampel feses dilakukan menggunakan sekuensing 16S rDNA full-length. Analisis statistik meliputi keragaman alpha (Chao1, Shannon, Simpson), keragaman beta (Bray-Curtis, NMDS), serta analisis komposisi taksonomi menggunakan Linear Discriminant Analysis Effect Size (LEfSe) dan Heat Tree.
Hasil: Tidak terdapat perbedaan signifikan pada karakteristik demografi dasar (usia, IMT, jenis kelamin) antara kelompok kasus dan kontrol (p > 0,05). Parameter klinis (indeks wayne, GO, dan goiter) menunjukkan perbedaan yang sangat signifikan (p < 0,001). Pasien graves menunjukkan kecenderungan keragaman alpha (indeks Chao1, Simpson, dan Shannon) yang lebih rendah dibandingkan kelompok normal. Analisis keragaman beta menunjukkan perbedaan struktur komunitas yang signifikan antara kedua kelompok. Analisis LEfSe mengidentifikasi peningkatan signifikan beberapa spesies dari genus Faecalibacterium pada kelompok graves. Berdasarkan tingkat keparahan (indeks wayne), analisis Heat Tree menunjukkan peningkatan signifikan Veillonellaceae dan penurunan Flintibacter pada kelompok Severe.
Kesimpulan: Terdapat hubungan yang signifikan antara tampilan klinis penyakit graves dengan disbiosis mikrobiota usus. Disbiosis ini ditandai dengan perubahan keragaman dan komposisi bakteri. Temuan utama adalah adanya peningkatan paradoksal genus Faecalibacterium pada pasien graves. Tingkat keparahan klinis berkorelasi dengan peningkatan bakteri pro inflamasi (Veillonellaceae) dan penurunan bakteri anti inflamasi (Flintibacter).
Kata Kunci: Penyakit Graves, Mikrobiota Usus, Disbiosis, Komposisi Mikrobiota, Keragaman Mikrobiota, Indeks Wayne, Faecalibacterium

Abstract ASSOCIATION OF GUT MICROBIOTA COMPOSITION AND DIVERSITY WITH THE CLINICAL FEATURES OF GRAVES DISEASE Background: Graves disease is a common autoimmune thyroid disorder, yet its pathogenesis is not fully understood. Recent scientific evidence suggests a role for gut microbiota dysbiosis in the development and progression of autoimmune diseases. This study aims to determine the relationship between the clinical presentation of graves disease and the composition and diversity of the gut microbiota. Methods: This was an observational study with a case-control design conducted at dr. Zainoel Abidin in Banda Aceh. A total of 48 subjects participated, comprising 24 newly diagnosed, treatment-naïve graves disease patients as the case group, and 24 healthy individuals as the control group. Clinical data (wayne index, GO grade, goiter grade) were recorded. Gut microbiota analysis from fecal samples was performed using full-length 16S rDNA sequencing. Statistical analysis included alpha diversity (Chao1, Shannon, Simpson), beta diversity (Bray-Curtis, NMDS), and taxonomic composition analysis using Linear Discriminant Analysis Effect Size (LEfSe) and Heat Tree. Results: There were no significant differences in basic demographic characteristics (age, BMI, gender) between the case and control groups (p > 0.05). Clinical parameters (Wayne Index, GO, and goiter) showed highly significant differences (p < 0.001). Graves patients showed a trend of lower alpha diversity (Chao1, Simpson, and Shannon indices) compared to the normal group. Beta diversity analysis indicated significant differences in community structure between the two groups. LEfSe analysis identified a significant increase in several species from the genus Faecalibacterium in the graves group. Based on severity (wayne index), the Heat Tree analysis revealed a significant increase in Veillonellaceae and a decrease in Flintibacter in the Severe group. Conclusion: There is a significant relationship between the clinical presentation of Graves disease and gut microbiota dysbiosis. This dysbiosis is characterized by changes in diversity (decreased alpha diversity and differing beta diversity) and bacterial composition. The main finding is a paradoxical increase in the genus Faecalibacterium in Graves patients. Clinical severity correlates with an increase in pro inflammatory bacteria (Veillonellaceae) and a decrease in anti inflammatory bacteria (Flintibacter). Keywords: Graves Disease, Gut Microbiota, Dysbiosis, Microbiota Composition, Microbiota Diversity, Wayne Index, Faecalibacterium