title: Abnormal weight gain and gut microbiota modifications are side effects of long-term doxycycline and hydroxychloroquine treatment.
abstract: 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 long-term doxycycline and hydroxychloroquine treatment. Gut microbiota modifications at the phylum level could play an instrumental role in this effect. We highlight the need for specific nutritional care in patients undergoing long-term antibiotic treatment, particularly treatment involving the use of doxycycline.
authors.affiliation: Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, Faculté de Médecine et de Pharmacie, CNRS UMR 7278, IRD 198, Aix-Marseille Université, Marseille, France.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Angelakis
authors.affiliation: Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, Faculté de Médecine et de Pharmacie, CNRS UMR 7278, IRD 198, Aix-Marseille Université, Marseille, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Million
authors.affiliation: UMR 912 SESSTIM, INSERM/IRD/Aix-Marseille Université, Faculté de Médecine, Marseille Cedex, France.
authors.forename: Sallah
authors.initials: S
authors.lastname: Kankoe
authors.affiliation: Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, Faculté de Médecine et de Pharmacie, CNRS UMR 7278, IRD 198, Aix-Marseille Université, Marseille, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Lagier
authors.affiliation: Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, Faculté de Médecine et de Pharmacie, CNRS UMR 7278, IRD 198, Aix-Marseille Université, Marseille, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Armougom
authors.affiliation: UMR 912 SESSTIM, INSERM/IRD/Aix-Marseille Université, Faculté de Médecine, Marseille Cedex, France.
authors.forename: Roch
authors.initials: R
authors.lastname: Giorgi
authors.affiliation: Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, Faculté de Médecine et de Pharmacie, CNRS UMR 7278, IRD 198, Aix-Marseille Université, Marseille, France didier.raoult@gmail.com.
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
mesh_terms: D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D004318:Doxycycline / Q000627:therapeutic use*; D004697:Endocarditis, Bacterial / Q000150:complications / Q000382:microbiology*; D004926:Escherichia coli; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use*; D007778:Lactobacillus; D008297:Male; D064307:Microbiota / Q000187:drug effects*; D008875:Middle Aged; D011778:Q Fever / Q000150:complications / Q000188:drug therapy*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D006886:Hydroxychloroquine; D004318:Doxycycline