Association of anti-TNF- treatment with gut microbiota of patients with ankylosing spondylitis

Objective Gut dysbiosis contributes to multiple autoimmune diseases, including ankylosing spondylitis. which is commonly treated with tumor necrosis factor (TNF)-alpha inhibitors (TNFis). Because host TNF-alpha levels are considered to interact with gut microbiota, we aimed to systematically investigate the microbiota profile of ankylosing spondylitis patients with anti-TNF-alpha-based treatment and identify potential key bacteria. Methods Fecal samples were collected from 11 healthy controls and 24 ankylosing spondylitis patients before/after anti-TNF-alpha treatment, the microbiota profiles of which were evaluated by 16S ribosomal DNA amplicon sequencing and subsequent bioinformatic analysis. Results Significantly different microbial compositions were observed in samples from ankylosing spondylitis patients compared with healthy controls, characterized by a lower abundance of short-chain fatty acid (SCFA)-producing bacteria. All patients exhibited a positive response after anti-TNF-alpha treatment, accompanied by a trend of restoration in the microbiota compositions and functional profile of ankylosing spondylitis patients to healthy controls. In particular, the abundance of SCFA-producing bacteria (e.g. Megamonsa and Lachnoclostridium) was not only significantly lower in ankylosing spondylitis patients than in healthy controls and restored after anti-TNF-alpha treatment but also negatively correlated with disease severity (e.g. cor=-0.52, P=8 x 10(-5) for Megamonsa). In contrast, Bacilli and Haemophilus may contribute to ankylosing spondylitis onset and severity. Conclusions Microbiota dysbiosis in ankylosing spondylitis patients can be restored after anti-TNF-alpha treatment, possibly by impacting SCFA-producing bacteria. Copyright (C) 2022 he Author(s). Published by Wolters Kluwer Health, Inc.