Butyrate, a postbiotic of intestinal bacteria, affects pancreatic cancer and gemcitabine response in in vitro and in vivo models

Biomedicine & Pharmacotherapy

Francesco Perri¹  Adele Potenza²  Fulvia Terracciano³  Concetta Panebianco³  Annacandida Villani³  Valerio Pazienza³  Federica Pisati⁴  Claudio Tripodo⁴  Fabrizio Orsenigo⁵  Tiziana Pia Latiano⁶  Annapaola Andolfo⁷  Marynka Ulaszewska⁷ 

[1]Tumor Immunology Unit, Department of Health Sciences, University of Palermo, Via del Vespro 129, 90127 Palermo, Italy

[2]Dietetic and Clinical Nutrition Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale dei Cappuccini, 1, 71013 San Giovanni Rotondo, FG, Italy

[3]Division of Gastroenterology, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale dei Cappuccini, 1, 71013 San Giovanni Rotondo, FG, Italy

[4]Histopathology Unit, Cogentech S.C.a.R.L, Via Adamello, 16, 20139 Milan, MI, Italy

[5]IFOM, FIRC Institute of Molecular Oncology, Milan, Italy

[6]Oncology Unit, Fondazione IRCCS ''Casa Sollievo della Sofferenza Hospital, Viale dei Cappuccini, 1, 71013 San Giovanni Rotondo, FG, Italy

[7]Proteomics and Metabolomics Facility (ProMeFa), IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132 Milan, Italy

关键词: Pancreatic cancer;    Microbiota;    Butyrate;    Gemcitabine response;   

DOI  :  

来源: DOAJ

【 摘 要 】

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer. The characteristic excessive stromatogenesis accompanying the growth of this tumor is believed to contribute to chemoresistance which, together with drug toxicity, results in poor clinical outcome. An increasing number of studies are showing that gut microbiota and their metabolites are implicated in cancer pathogenesis, progression and response to therapies. In this study we tested butyrate, a product of dietary fibers’ bacterial fermentation, whose anticancer and anti-inflammatory functions are known. We provided in vitro evidence that, beside slowing proliferation, butyrate enhanced gemcitabine effectiveness against two human pancreatic cancer cell lines, mainly inducing apoptosis. In addition, we observed that, when administered to a PDAC mouse model, alone or combined with gemcitabine treatment, butyrate markedly reduced the cancer-associated stromatogenesis, preserved intestinal mucosa integrity and affected fecal microbiota composition by increasing short chain fatty acids producing bacteria and decreasing some pro-inflammatory microorganisms. Furthermore, a biochemical serum analysis showed butyrate to ameliorate some markers of kidney and liver damage, whereas a metabolomics approach revealed a deep modification of lipid metabolism, which may affect tumor progression or response to therapy. Such results support that butyrate supplementation, in addition to conventional therapies, can interfere with pancreatic cancer biology and response to treatment and can alleviate some damages associated to cancer itself or to chemotherapy.

【 授权许可】

Unknown