Golimumab Effect in the Modulation of Gut Microbiota in Ulcerative Colitis: Pilot Study

Golimumab effect in the modulation of gut microbiota in Ulcerative Colitis. Pilot Study.

1. BACKGROUND Recently, a consistent body of evidence indicates that the gut microbiota ability to modulate and direct the host immune response is considered one of the pivotal factors that modulate the delicate balance between health and disease in digestive diseases. In the case of inflammatory bowel disease (IBD), the gut microbiota has a central role in maintaining the microbiological homeostasis of the patient. Recent studies describe the existence of different patterns of intestinal microbiota from patients with IBD and healthy individuals . The alteration of the microbiological pattern not associated with disease is known as dysbiosis and is directly related to the degree of inflammation of the intestinal mucosa, and, thus, the clinic status: a greater dysbiosis, greater clinical correlation with disease state, so that the gut microbiota is a direct marker of the state of colonic inflammation .

The state of dysbiosis is measured through different microbiological indices of the total population of bacteria in the colon. Changes in rates of these indices are the parameters that are measured to characterize the gut microbiota of the patients. In the case of ulcerative colitis (UC) studies have shown that intestinal microbiota is a central factor in maintaining the balance between deep remission and the presence of a flare-up. Despite advances, in-depth knowledge of how the gut microbiota interacts with the intestinal mucosa and alters the intestinal barrier and the molecular/genetic mechanism is still unknown. Some genes and associated cofactors have been identified but the exact mechanism of interaction has not yet been described. The data indicate that, presumably, the mechanism of regulation is a multifactorial process.

In this way, a deep understanding of gut microbiota and its interactions with the host and the colon will be of great interest, in order to shape the future of IBD treatment, especially of UC. Thus, IBD patients' intestinal microbiota could be either a therapeutic target itself (fecal transplantation) or be consider as an adjustable adjuvant with immunomodulators The group of anti-TNF drugs are the most recently incorporated in the therapeutic arsenal of UC, in some cases changing the natural curse of the disease. However, it is still unknown how these drugs modulate the intestinal microbiota and how they interfere with it, although, probably, they develop a role. Recent results from studies by our group, indicate that on entering clinical remission, gut microbiota is modified to patterns less related with dysbiosis. Given the increasing importance of the use of anti-TNF drugs, it is of great interest to discriminate between the patterns associated with dysbiosis and those related with healthy mucosa, and how they are modified as a result of the use of anti-TNF drugs. In this way, previous results of our group analyzing the changes of intestinal microbiota associated with Adalimumab anti-TNF drug treatment have shown that during the progression of the patient into remission, the mucosal dysbiosis pattern changes. On the other hand, our group has also observed that after drug treatment failure, the gut microbiota returns to a pattern closer to dysbiosis. For that reason, gut microbiota could be considered as an excellent indicator of the real drug effectiveness in the patient.

Regarding Golimumab, a recently introduced anti-TNF drug therapy in UC, it is still unknown how it is able to modulate the intestinal microbiota to remission-related patterns, since to date there are not available studies about the relationship between Golimumab and this phenomenon.