**2.4 Synbiotics**

Synbiotics represents a combination of prebiotics and probiotics with synergistic beneficial effect, but for now there are still few literature data on their effect on IBD patients; more often, they contain Lactobacillus GG and/or Bifidobacteria combined with FOS and/or inulin [67, 68]. In the double-blind trial of Steed et al. [69], patients with active CD were randomized to receive 6 g per day of either a synbiotic (a combination of inulin and FOS) vs. placebo for 6 months. The results demonstrated significant reduction in the clinical and histopathological activity of CD, an increased population of Bifidobacteria species in the study group, and a decrease in TNF alpha after 3 months (but not 6 months). Another randomized, double-blind and placebo-controlled study [70] evaluated the same symbiotic for a period of 1 month, revealing significant improvement in the endoscopic and histopathological activity in the rectal biopsies and reduction in serum CRP, TNF-α, and IL-1 α and mucosal human beta defensins 2, 3, 4.

The randomized, double-blind and placebo-controlled trial of Chermesh et al. [71] investigated Synbiotic 2000 including four probiotics and four prebiotics administrated for 24 months found no significant differences between the study group and placebo regarding clinical picture, laboratory data, and endoscopic activity. Fujimori et al. [72] included 120 patients with UC (active and inactive) that were randomized into three groups, first treated with probiotic (Bifidobacterium longum), the second with prebiotic (Psyllium), and the third one with symbiotic (bifidobacterium longum plus psyllium) for 4 weeks, observing a significant improvement in the QoL and decrease in CRP level in the group treated with symbiotic vs. the other two groups. Another study investigated 41 patients with mild-to-moderate UC, randomized into two groups, one with standard treatment associated with symbiotic (Bifidobacterium breve strain Yakult plus GOS) vs. the second group treated only with standard treatment. After 1 year of treatment, authors noticed significant reduction in clinical and endoscopic activity in study group vs. control [73].
