Intestinal microbiota changes induced by TNF-inhibitors in IBD-related spondyloarthritis

Abstract

BackgroundThe close relationship between joints and gut inflammation has long been known and several data suggest that dysbiosis could link spondyloarthritis (SpA) to inflammatory bowel diseases (IBD). The introduction of biological drugs, in particular tumour necrosis factor inhibitors (TNFi), revolutionised the management of both these diseases. While the impact of conventional drugs on gut microbiota is well known, poor data are available about TNFi.AimTo investigate the impact of TNFi on gut microbiota.MethodsWe evaluated 20 patients affected by enteropathic arthritis, naïve for biological drugs, treated with TNFi at baseline and after 6 months of therapy. All patients followed a Mediterranean diet. Patients performed self-sampling of a faecal sample at baseline and after 6 months of therapy. NGS-based ITS and 16S rRNA gene sequencing was performed, followed by the taxonomic bioinformatics analysis.ResultsAfter 6 months of therapy, we detected a remarkable increase in Lachnospiraceae family (Δ +10.3, p=0.04) and Coprococcus genus (Δ +2.8, p=0.003). We also noted a decreasing trend in Proteobacteria (Δ −8.0, p=0.095) and Gammaproteobacteria (Δ −9, p=0.093) and an increasing trend in Clostridia (Δ +8.2, p=0.083). We did not find differences between TNFi responders (SpA improvement or IBD remission achieved) and non-responders in terms of alpha and beta diversity.ConclusionsOur findings are consistent with the hypothesis that TNFi therapy tends to restore the intestinal eubiosis.

The Role of the Microbiota in Graves’ Disease and Graves’ Orbitopathy

“…Like AZA, the anti-TNF-α antibody can restore intestinal microbial diversity in patients with Crohn’s disease by decreasing Proteobacteria but increasing Bacteroidetes ( Effenberger et al., 2021 ). In 20 enteropathic arthritis patients who followed a Mediterranean diet, anti-TNF-α antibody treatment for 6 months could increase Lachnospiraceae family and Coprococcus genus and also induce a decreasing trend in Proteobacteria and Gammaproteobacteria and an increasing trend in Clostridia ( Ditto et al., 2021 ).…”

Role of the microbiome and its metabolites in ankylosing spondylitis

“…In mice, etanercept treatment restored intestinal microbiota composition similar to control mice (174). YIN et al ( 19) and Maria et al (175) found that TNFi treatment substantially restored the disturbed microbiome observed in untreated AS Potential methods for therapeutic intervention targeting the gut microbiota. Antibiotics may eliminate harmful bacteria in the gut.…”

“…( 19 ) and Maria et al. ( 175 ) found that TNFi treatment substantially restored the disturbed microbiome observed in untreated AS cases, including several critical bacterial species previously associated with AS and other related diseases, compared to HCs. In a study exploring responses to anti-TNF-α therapy, AS patients had a lower microbiota diversity at baseline than HCs at the same level but returned to normal after one month of treatment ( 12 ).…”

Levofloxacin induces differential effects in the transcriptome between the gut, peripheral and axial joints in the Spondyloarthritis DBA/1 mice: Improvement of intestinal dysbiosis and the overall inflammatory process

“…Moreover, in HLA-B27-positive transgenic rats, Prevotella dysregulates the key pathogenic cytokines, including IL-17, IL-23, and TNF-α [42,43]. Blautia [44], Odoribacter [45], Rikinella [43,46], Bacteroides [47,48], Parabacteroides [17,49], Desulfovibrio [50,51], Streptococcus [52][53][54][55], and Clostridia [56][57][58][59] are associated with the dysbiosis in patients with SpA and/or in animal models of the human disease. Most of these bacteria primarily have pro-inflammatory potential; Desulfovibrio and Parabacteroides [60,61] also have anti-inflammatory potential.…”