Abnormal Weight Gain and Gut Microbiota Modifications Are Side Effects of Long-Term Doxycycline and Hydroxychloroquine Treatment

作者：Emmanouil Angelakis, Matthieu Million, Sallah Kankoe, Jean‐Christophe Lagier, Fabrice Armougom, Roch Giorgi, Didier Raoult · 发表于：Antimicrobial Agents and Chemotherapy · 年份：2014 · DOI：10.1128/aac.02437-14 · 被引用次数：98 · 研究领域：Gut microbiota and health、Clostridium difficile and Clostridium perfringens research、Ginseng Biological Effects and Applications

Doxycycline has been proposed for the treatment of malnourished children in developing countries, and its use has been associated with weight gain in healthy volunteers. No previous studies have assessed abnormal weight gain as a putative side effect of long-term doxycycline treatment; thus, the objective of the present study was to characterize this phenomenon. We also analyzed the role of the gut microbiota in this effect. We assessed changes in the body mass index in Q fever endocarditis patients treated with doxycycline and hydroxychloroquine and healthy individuals with no antibiotic treatment. Abnormal weight gain was defined as a gain in weight above that of the controls. The fecal samples were examined using molecular assays for Methanobrevibacter smithii, Bacteroidetes, Firmicutes, Escherichia coli, Lactobacillus, Lactobacillus reuteri, and total bacterial concentrations. We examined 82 patients, including 48 patients with Q fever endocarditis and 34 controls. Approximately 23% of the treated patients showed abnormal weight gain (P = 0.001). Patients treated with doxycycline and hydroxychloroquine presented significantly lower concentrations of Bacteroidetes (P = 0.002), Firmicutes (P = 0.01), and Lactobacillus (P = 0.02). The linear regression analysis revealed that the duration of treatment was significantly associated with a decrease in Bacteroidetes (P = 0.0001), Firmicutes (P = 0.002), and total bacteria (P < 0.00001). Abnormal weight gain is a side effect of lo...