The intestinal microbiota, a predictor of response to anti-TNF alpha therapy?

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Characterization of the intestinal microbiota could allow the efficacy of treatment with TNFa inhibitors to be predicted in patients suffering from ankylosing spondylitis. The presence of bacteria of the Burkholderiales order is thought to be synonymous with a better response to treatment, according to the results of a French team.

 

Ankylosing spondylitis (AS) is an inflammatory rheumatic disease which mainly affects the spine and the lower back. Its etiology is beginning to be elucidated: genetic and environmental factors (especially smoking) have been identified, but they are not enough to explain all the pathophysiological phenomena observed. In this regard, the intestinal microbiota and its variations in subjects suffering from spondylitis treated for the first time with an anti-TNFa agent* represent another clue.

Treatment has little impact on the microbiota

Changes in the intestinal populations of 18 subjects were tracked by sequencing bacterial DNA from fecal samples collected before and three months after the start of treatment. The objective was to identify any microbial specificities, according to whether or not the individual responded to treatment. Probably because of its low statistical power, the study ultimately revealed that taking a TNFa inhibitor caused only a slight change in the concentration of the most representative taxa: Firmicutes, Bacteroidetes, Tenericutes and Proteobacteria. Patients who did not respond to treatment however presented with larger variations in the composition of their intestinal microbiotas than patients who did respond, after 0 and 3 months of treatment. This difference could be linked to a “normalizing” action, with the microbiota of the first group being initially less uniform than that of the second.

A bacterium as a biomarker of a positive response

The most noteworthy result remains the identification of a taxon whose abundance at T0 was associated with a positive clinical result at three months: bacteria of the order Burkholderiales (Betaproteobacteria class). The presence of these bacteria could therefore represent a biomarker that would allow prior identification of patients who are likely to respond to treatment with a TNFa inhibitor. A potential opportunity to improve the management of all patients while optimizing health care costs, but which requires a prospective study phase.

 

*Anti-TNFa agents are monoclonal antibodies that behave as soluble Tumor Necrosis Factor alpha (TNFα) receptors. TNFa is a cytokine which has proinflammatory and immunoregulatory properties.

 

Sources:

T. Bazin, K. Hooks, T. Barnetche, et al. Microbiota Composition May Predict Anti-Tnf Alpha Response in Spondyloarthritis Patients: an Exploratory Study, Nature Scientific Reports | (2018) 8:5446 | DOI:10.1038/s41598-018-23571-4