Electronic Theses and Dissertation

Tuberkulosis (TBC) merupakan penyebab kematian utama penyakit menular, terutama di negara berkembang seperti Indonesia. Mikrobiota berperan penting dalam fisiologi tubuh dan mempengaruhi patogenesis penyakit infeksi melalui regulasi sistem imunitas tubuh. Salah satu metabolit yang dihasilkan oleh mikrobiota usus dari metabolisme asam amino triptofan (Trp) adalah derivat indole, indole propionic acid (IPA). M. Tb memerlukan biosintesis Trp untuk bertahan hidup dari stres oleh sel T CD4 dan IFN-γ dalam makrofag alveolar, sementara IPA dapat berperan sebagai anti-mikobakterial secara in vitro dan in vivo melalui penghambatan jalur biosintetik Trp pada M. Tb. Namun, penelitian tentang metabolit IPA pada pasien TBC belum dilakukan. Oleh karena itu, penelitian ini bertujuan menganalisis perbedaan kadar IPA pada pasien TBC dan subjek sehat, serta menganalisis hubungan antara kadar IPA dengan karakteristik pasien, kadar IFN-γ, serta kelimpahan relatif mikrobiota usus yang membantu produksi IPA, yaitu Clostridium sporogenes, Peptostreptococcus anaerobius dan Lactobacillus sp. Penelitian dengan desain case control ini merekrut 29 pasien TBC yang terkonfirmasi secara bakteriologis dan 30 orang sehat. Kadar IPA plasma kelompok pasien TBC aktif lebih tinggi secara signifikan dibandingkan orang sehat pada model unadjusted (median [IQR]; 22.2 pmol/L [21.3-23.9)] vs. 18.9 pmol/L [17-22.8], p-value

Tuberculosis (TBC) is the main cause of death in communicable diseases globally, especially in developing countries, including Indonesia. Microbiota plays an important role in the physiology of the human health and influences infectious disease pathogenesis through regulation of the immune system. One of the metabolites produced from the tryptophan (Trp) metabolism by gut microbiota is an indole derivative, indole propionic acid (IPA). As M. Tb requires Trp biosynthesis to survive from stress by CD4 T cells and IFN-γ in alveolar macrophages, IPA acts as anti-mycobacterial in vitro and in vivo through inhibition of the Trp biosynthetic pathway in M. Tb. However, studies on IPA metabolites in TBC patients have not been carried out. Therefore, the aim of this study was to analyze differences of IPA levels in TB patients and healthy subjects, as well as analyze the relationship between IPA levels and patient characteristics, IFN-γ levels, and the relative abundance of IPA producing-gut microbiota, namely Clostridium sporogenes, Peptostreptococcus anaerobius and Lactobacillus sp. The case control design study recruited 29 active TB patients who were bacteriologically confirmed, and 30 healthy subjects as controls. Plasma IPA levels of active TB patients were significantly higher than those in healthy individuals in unadjusted model (median [IQR]; 22.2 pmol/L [21.3-23.9)] vs. 18.9 pmol/L [17-22.8], p-value