Editorial: mesalazine and mucosal microbiome in quiescent ulcerative colitis—what can we learn?

Abstract

Patients with IBD have an altered gut microbiome; these alterations are defined as dysbiosis. Reduced diversity, abundance of pro‐in‐ flammatory bacteria such as Enterobacteriaceae, reduction in phyla with anti‐inflammatory properties such as Firmicutes have been re‐ ported.1,2 Mechanisms of efficacy of pharmacotherapy or markers of response and relationships to dysbiosis have been of special in‐ terest. Ananthrakrishnan et al3 looked specifically into longitudinal changes of the gut microbiome and correlated them with response to drug therapy to determine whether the microbiome may predict response.3 The association between baseline taxonomic composi‐ tion and functional pathways abundance and the ability of a patient with IBD to achieve clinical remission at week 14 after initiation of treatment with anti‐integrin therapy have been confirmed.3 Intestinal bacteria are believed to play a role in causing or per‐ petuating IBD and bioremediation has been studied as a therapeutic strategy. To better understand the bacteriological effects of 5‐ASA, its ability to alter bacterial microbiota composition and its relation‐ ship to response to therapy have been investigated.4,5 Xu et al4 demonstrated in untreated UC patients that Firmicutes (e.g. Enterococcus) were decreased and Proteobacteria (e.g. Escherichia, Shigella) were increased in inflamed mucosa. There was a higher abundance of Firmicutes and lower levels of Proteobacteria in the inflamed mucosa of 5‐ASA‐treated patients. By decreasing polyphosphate levels in diverse bacteria, mesalazine may diminish bacterial persistence within inflamed mucosa.5 The recent study by Dr. Olaisen et al6 in AP&T adds a valid argu‐ ment for the influence of 5‐ASA on the mucosal microbiome. The study aimed to evaluate the relationship between 5‐ASA concen‐ trations, 5‐ASA formulations, N‐acyl transferase (NAT) genotype and bacterial microbiome in 42 patients with UC. However, it fo‐ cused only on patients with quiescent UC undergoing monotherapy with either Mezavant (i.e. Lialda or MMX mesalazine), Asacol (de‐ layed‐release mesalazine) or Pentasa (i.e. extended‐release mesal‐ azine). MMX mesalazine provided the highest mucosal 5‐ASA level, followed by delayed‐release and extended‐release mesalazine. Mucosal 5‐ASA concentration was positively associated with muco‐ sal bacterial diversity and bacterial compositions. Specifically, high mucosal 5‐ASA concentration was related to the reduced abundance of pathogenic bacteria such as Proteobacteria and increased abun‐ dance of several favourable bacteria such as Faecalibacterium. 5‐ASA may have beneficial effects on the mucosal microbiome and high concentrations alter dysbiosis in UC. While the study clearly high‐ lighted that mucosal 5‐ASA concentration is associated with changes in mucosal bacterial composition, it did not demonstrate alteration of faecal microbiota to the same extent. The use of 16S rRNA se‐ quence to analyse the intestinal microbiome may not be preferred long term. Analysis of faecal bacteriome could be more applicable if future studies demonstrated utility. This study showed that 5‐ASA increases bacterial diversity, fa‐ vouring beneficial bacteria and inhibiting potential harmful bacte‐ ria in UC patients. However, we may still question the mechanisms behind these associations and how we can apply these results in our UC patients. Further studies are needed to define alterations of the microbiome and faecal bacteriome with 5‐ASA in patients with active and quiescent disease.