Profiling the Effects of Systemic Antibiotics for Acne, Including the Narrow-Spectrum Antibiotic Sarecycline, on the Human Gut Microbiota

Abstract

Treatment for moderate-to-severe acne vulgaris relies on prolonged use of oral tetracycline-class antibiotics; however, these broad-spectrum antibiotics are often associated with off-target effects and negative gastrointestinal sequelae. Sarecycline is a narrow-spectrum antibiotic treatment option. Here, we investigated the effect of prolonged sarecycline exposure, compared with broad-spectrum tetracyclines (doxycycline and minocycline) upon the colonic microbiota. Three in vitro models of the human colon were instilled with either minocycline, doxycycline or sarecycline, and we measured microbiota abundance and diversity changes during and after antibiotic exposure. Significant reductions in microbial diversity were observed following minocycline and doxycycline exposure, which failed to recover post antibiotic withdrawal. Specifically, minocycline caused a ~10% decline in Lactobacillaceae and Bifidobacteriaceae abundances, while doxycycline caused a ~7% decline in Lactobacillaceae and Bacteroidaceae abundances. Both minocycline and doxycycline were associated with a large expansion (>10%) of Enterobacteriaceae. Sarecycline caused a slight decline in bacterial diversity at the start of treatment, but abundances of most families remained stable during treatment. Ruminococcaceae and Desulfovibrionaceae decreased 9% and 4%, respectively, and a transient increased in Enterobacteriaceae abundance was observed during sarecycline administration. All populations recovered to pre-antibiotic levels after sarecycline exposure. Overall, sarecycline had minimal and transient impact on the gut microbiota composition and diversity, when compared to minocycline and doxycycline.

MiGut: A scalable in vitro platform for simulating the human gut microbiome—Development, validation and simulation of antibiotic‐induced dysbiosis

“…Each of the faecal slurries was prepared by pooling faecal samples from five healthy volunteers without history of antibiotic therapy or prescription of proton pump inhibitors in the 3 months prior to sample collection, as previously described (Moura et al, 2022 ; Roberts et al, 2020 ). Samples were homogenised with phosphate‐buffered saline to a 1:10 weight ratio (Buckley, Moura, Arai, et al, 2021 ).…”

“…By arranging multiple vessels in series, it is possible to simulate different colonic environments, as has been demonstrated with various gut model systems in the literature (SHIME: Van de Wiele et al, 2015 ; TIM: Minekus, 2015 ; PolyFermS: Zihler Berner et al, 2013 ; EnteroMix: Mäkivuokko et al, 2006 ). A triple‐stage chemostat model ( Supporting Information, Section 2 ) based on the original work by Gibson et al ( 1988 ) has been extensively used by our team for over two decades to investigate the effects of antibiotics on the GM and the pathogenesis of infections caused, for example, by C. difficile and multi‐drug resistant Gram‐negative bacteria (Begum et al, 2020 ; Best et al, 2012 ; Buckley, Altringham, et al, 2021 ; Buckley, Moura, Altringham, et al, 2021 ; Crowther et al, 2016 ; Harris et al, 2021 ; Moura et al, 2019 , 2022 ; Rooney et al, 2019 ). This human gut model (HGM) has been previously validated against human gut content of sudden death victims, with samples taken from the proximal, medial and distal colonic regions closely matching the microbial in vitro populations in vessels 1, 2 and 3 of the triple‐stage model, respectively (Macfarlane et al, 1998 ).…”

Interim position statement on doxycycline post-exposure prophylaxis (Doxy-PEP) for the prevention of bacterial sexually transmissible infections in Australia and Aotearoa New Zealand – the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM)

“…Doxycycline use has been associated with a loss of diversity in the human gut microbiome, 32 and disturbances of the gut microbiome have been linked to a broad range of chronic diseases, ranging from diabetes, to autoimmune diseases and mental health disorders. 33 As one concrete example, tetracyclines such as doxycycline are used to promote weight gain in livestock, and this effect is thought to be mediated by effects on animals' gut microbiome.…”

Bidirectional Interaction between Tetracyclines and Gut Microbiome

“…Failure to recover to pre-treatment levels in some bacteria Reduction in microbial richness Increase in opportunistic bacteria [49,68,71,72] Table 7. RESERVE antibiotics' mechanisms of dysbiosis.…”