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

Abstract

b 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.

Sorting out adipocyte precursors and their role in physiology and disease

“…Auwerx and colleagues (Chatzispyrou et al 2015;Moullan et al 2015) demonstrated that doxycycline negatively impacts mitochrondrial function. Doxycycline can also impact the gut microbiota in humans; the direct impact of this on adipose biology is unclear but potentially significant (Angelakis et al 2014). Furthermore, doxycycline can regulate the function of matrix metalloproteinases (Stechmiller et al 2010).…”

Sexually transmissible infection control programs for men who have sex with men – what will they look like in 2020?

“…Although doxycycline is prescribed long term for conditions ranging from acne to malaria, while generally safe, its prolonged use has been rarely associated with irritable bowel syndrome, abnormal weight gain and photosensitivity. [34][35][36] Currently, a few laboratories are researching vaccines to prevent bacterial STIs. While no vaccine is imminent, continued research may generate a product for further evaluation.…”

Adrenomedullin regulates intestinal physiology and pathophysiology

“…Twenty-eight mice (>50 wk) were divided in WT males (WTM), WT females (WTF) knockout males (KOM), and knockout females (KOF). All of them were treated with doxycycline to avoid differences caused by the antibiotic because it has been proven that doxycycline administration not only alters the microbiota composition [203] it also significantly modifies the expression of important cellular pathways [204]. A month after completing the doxycycline treatment, fresh stool was obtained from each animal in a noninvasive way and analyzed by real-time PCR with specific primers for the 4 most dominant orders of gut bacteria: Enterobacteriales, Lactobacillales, Bacteroidales, and Clostridiales [205].…”