title: Engineered Resistant-Starch (ERS) Diet Shapes Colon Microbiota Profile in Parallel with the Retardation of Tumor Growth in In Vitro and In Vivo Pancreatic Cancer Models.
abstract: OBJECTIVE
  Pancreatic cancer (PC) is ranked as the fourth leading cause of cancer-related deaths worldwide. Despite recent advances in treatment options, a modest impact on the outcome of the disease is observed so far. We have previously demonstrated that short-term fasting cycles have the potential to improve the efficacy of chemotherapy against PC. The aim of this study was to assess the effect of an engineered resistant-starch (ERS) mimicking diet on the growth of cancer cell lines in vitro, on the composition of fecal microbiota, and on tumor growth in an in vivo pancreatic cancer mouse xenograft model.
  
  
  METHODS
  BxPC-3, MIA PaCa-2 and PANC-1 cells were cultured in the control, and in the ERS-mimicking diet culturing condition, to evaluate tumor growth and proliferation pathways. Pancreatic cancer xenograft mice were subjected to an ERS diet to assess tumor volume and weight as compared to mice fed with a control diet. The composition and activity of fecal microbiota were further analyzed in growth experiments by isothermal microcalorimetry.
  
  
  RESULTS
  Pancreatic cancer cells cultured in an ERS diet-mimicking medium showed decreased levels of phospho-ERK1/2 (extracellular signal-regulated kinase proteins) and phospho-mTOR (mammalian target of rapamycin) levels, as compared to those cultured in standard medium. Consistently, xenograft pancreatic cancer mice subjected to an ERS diet displayed significant retardation in tumor growth. In in vitro growth experiments, the fecal microbial cultures from mice fed with an ERS diet showed enhanced growth on residual substrates, higher production of formate and lactate, and decreased amounts of propionate, compared to fecal microbiota from mice fed with the control diet.
  
  
  CONCLUSIONS
  A positive effect of the ERS diet on composition and metabolism of mouse fecal microbiota shown in vitro is associated with the decrease of tumor progression in the in vivo PC xenograft mouse model. These results suggest that engineered dietary interventions could be supportive as a synergistic approach to enhance the efficacy of existing cancer treatments in pancreatic cancer patients.
authors.affiliation: Gastroenterology Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza", Hospital, San Giovanni Rotondo (FG) 71013, Italy. panebianco.c@gmail.com.
authors.forename: Concetta
authors.initials: C
authors.lastname: Panebianco
authors.affiliation: Department of Food Processing, Tallinn University of Technology, Tallinn 12616, Estonia. kaarel.adamberg@ttu.ee.|Competence Center of Food and Fermentation Technologies, Tallinn 12616, Estonia. kaarel.adamberg@ttu.ee.
authors.forename: Kaarel
authors.initials: K
authors.lastname: Adamberg
authors.affiliation: Department of Food Processing, Tallinn University of Technology, Tallinn 12616, Estonia. signe.adamberg@gmail.com.
authors.forename: Signe
authors.initials: S
authors.lastname: Adamberg
authors.affiliation: Gastroenterology Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza", Hospital, San Giovanni Rotondo (FG) 71013, Italy. chiarasaracino88@gmail.com.
authors.forename: Chiara
authors.initials: C
authors.lastname: Saracino
authors.affiliation: Competence Center of Food and Fermentation Technologies, Tallinn 12616, Estonia. madis.jaagura@ttu.ee.|Department of Chemistry, Tallinn University of Technology, Tallinn 12616, Estonia. madis.jaagura@ttu.ee.
authors.forename: Madis
authors.initials: M
authors.lastname: Jaagura
authors.affiliation: Department of Chemistry, Tallinn University of Technology, Tallinn 12616, Estonia. kaia.kolk@ttu.ee.
authors.forename: Kaia
authors.initials: K
authors.lastname: Kolk
authors.affiliation: Tamma Industrie Alimentari di Capitanata (FG), Foggia 71100, Italy. adichio@tamma.it.
authors.forename: Anna Grazia
authors.initials: AG
authors.lastname: Di Chio
authors.affiliation: Pathology Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza", Hospital, San Giovanni Rotondo (FG) 71013, Italy. p.graziano@operapadrepio.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Graziano
authors.affiliation: Competence Center of Food and Fermentation Technologies, Tallinn 12616, Estonia. raivo@kbfi.ee.|Department of Chemistry, Tallinn University of Technology, Tallinn 12616, Estonia. raivo@kbfi.ee.
authors.forename: Raivo
authors.initials: R
authors.lastname: Vilu
authors.affiliation: Gastroenterology Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza", Hospital, San Giovanni Rotondo (FG) 71013, Italy. pazienza_valerio@yahoo.it.
authors.forename: Valerio
authors.initials: V
authors.lastname: Pazienza
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003106:Colon / Q000382:microbiology*; D004269:DNA, Bacterial / Q000302:isolation & purification; D004032:Diet; D004195:Disease Models, Animal; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome; D051379:Mice; D008819:Mice, Nude; D020928:Mitogen-Activated Protein Kinases; D010190:Pancreatic Neoplasms / Q000178:diet therapy*; D013213:Starch / Q000008:administration & dosage* / Q000737:chemistry; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D004269:DNA, Bacterial; D013213:Starch; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases
keywords: functional food; microbiota; pancreatic cancer