Butyrate is a short-chain fatty acid that plays a key role in maintaining gut homeostasis as well as the integrity of the intestinal barrier. In the present study, we investigated the effect of oral microencapsulated sodium butyrate (BLM) administration in maintaining remission and improving residual symptoms and inflammatory markers in a population of patients with ulcerative colitis (UC). Forty-two patients with UC in clinical remission were enrolled in the study. Three patients were lost to follow up; 39 patients (18 treated with BLM add-on therapy and 21 with standard mesalamine only) that reached 12 months of follow up were included in the final analysis. Therapeutic success (defined as Mayo partial score ≤ 2 and faecal calprotectin (FC) < 250 µg/g at 12 months of follow up) was achieved in 25 patients (64.1%); 15/18 (83.3%) in BLM group and 10/21 (47.6%) in control group (p = 0.022). Consistently, 13/18 patients (72.2%) receiving BLM improved residual symptoms compared to 5/21 patients (23.8%) in control group (p = 0.003). FC values significantly diminished from the baseline to the end of follow up in patients that received BLM, while FC values remained almost stable in the control group. In conclusion, oral BLM supplementation appears to be a valid add-on therapy in order to maintain remission in patients with UC. Further randomized, placebo-controlled, double-blind clinical trials are needed to validate our results on a larger population or cohort of patients.

Several compounds based on short chain fatty acids and/or probiotics/prebiotics have shown promising results in the therapy of ulcerative colitis (UC), possibly due to its key role in restoring gut homeostasis as well as intestinal barrier integrity. Here, we investigated the efficacy of a patented preparation based on calcium butyrate, Bifidobacterium bifidum, Bifidobacterium lactis, and fructooligosaccharides (FEEDColon®, Princeps, Cuneo, Italy) in maintaining remission and improving subjective symptoms and inflammatory indices in patients with UC receiving 5-ASA therapy. A total of 42 patients were prospectively recruited and randomized in 21 patients receiving combination therapy with mesalamine (5-ASA) plus FEEDColon® and 21 patients treated with standard 5-ASA therapy. Patients were assessed at baseline, at 6-month, and 12-month follow-up (FU). Therapeutic success (defined as Mayo partial score ≤ 2 and faecal calprotectin (FC) < 250 µg/g at 12-month FU) was reached by 32 (76%) patients: 20 (95%) among those treated with 5-ASA + FeedColon®, and 12 (57%) among those treated with 5-ASA only (p = 0.009). Consistently, patients treated with combination therapy improved subjective symptoms (quality of life, abdominal pain, and stool consistency) and reduced FC values, while those treated with 5-ASA alone, improved neither subjective symptoms nor FC during the FU. In conclusion, FEEDColon® supplementation appears to be a valid add-on therapy for the maintenance of remission in patients with UC. Further multicentre, placebo-controlled, double-blind clinical trials are needed to validate our results on larger cohorts of patients with UC.

Cholangiocarcinoma (CCA) is an aggressive neoplasia with an increasing incidence and mortality. It is characterized by a strong desmoplastic stroma surrounding cancer cells. Cancer-associated fibroblasts (CAFs) are the main cell type of CCA stroma and they have an important role in modulating cancer microenvironments. CAFs originate from multiple lines of cells and mainly consist of fibroblasts and alpha-smooth muscle actin (α-SMA) positive myofibroblast-like cells. The continuous cross-talking between CCA cells and desmoplastic stroma is permitted by CAF biochemical signals, which modulate a number of pathways. Stromal cell-derived factor-1 expression increases CAF recruitment to the tumor reactive stroma and influences apoptotic pathways. The Bcl-2 family protein enhances susceptibility to CAF apoptosis and PDGFRβ induces fibroblast migration and stimulates tumor lymphangiogenesis. Many factors related to CAFs may influence CCA prognosis. For instance, a better prognosis is associated with IL-33 expression and low stromal IL-6 (whose secretion is stimulated by microRNA). In contrast, a worst prognosis is given by the expression of PDGF-D, podoplanin, SDF-1, α-SMA high expression, and periostin. The maturity phenotype has a prognostic relevance too. New therapeutic strategies involving CAFs are currently under study. Promising results are obtained with anti-PlGF therapy, nintedanib (BIBF1120), navitoclax, IPI-926, resveratrol, and controlled hyperthermia.

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