The gut microbiome in IBD is characterized by impaired metabolic cooperativity and can be restored upon anti-TNFα therapy

Background and aims:

Blocking TNFα is an important treatment option for inflammatory bowel disease (IBD). The etiology of the disorder comprises a permanent activation of immune cascades and imbalanced cytokine networks. Evidence has been put forward that alteration of the human gut microbiome may play a critical role in the pathogenesis of IBD. However, the impact of targeted cytokine blockade on dysbiosis of intestinal microbial communities is poorly understood. Here, we investigate the effect of anti-TNFα treatment on gut microbial community structures in a prospective, longitudinal study for 30 weeks. The study compares IBD as a disorder, which primarily affects the gut, with seropositive and -negative rheumatoid arthritis and ankylosing spondylitis as a rheumatic disorder (RD) as an inflammatory disease complex, which usually does not affect the intestine.

Methods:

anti-TNFα naive patients suffering from IBD (n = 12) or RD (n = 17), subject to first-time anti-TNFα therapy were recruited for longitudinal stool sampling at baseline and 2, 6 and 30 weeks after therapy induction. Intestinal microbiota communities were studied by 16S rRNA gene (V4) sequencing. Changes in microbiota before and after therapeutic interventions were assessed in terms of alpha and beta diversity, indicator species and prediction of metabolic cooperative interactions. Samples from healthy controls (n = 19) were included as a benchmark of healthy microbial profiles.

Results:

Intestinal microbial diversity and cooperativity are decreased in both disease entities, IBD and RA. In IBD, anti-TNFα therapy is able to restore microbial diversity and cooperativity. More over cooperative metabolic interaction is significantly increased only in anti-TNFα responders. In RA, anti-TNFα therapy did not significantly restore microbial community structures.

Conclusion:

We show that anti-TNFα treatment increases the gut microbial diversity and coupling of cross feeding metabolic interactions towards the state of healthy individuals. Assessment of metabolic interactions of intestinal microbiota may serve as a marker for clinical response in IBD patients.