title: Bacterial translocation is reduced by a specific nutritional combination in mice with chemotherapy-induced neutropenia.
abstract: Immune function is compromised in many cancer patients, leading to an increased risk of (infectious) complications. Chemotherapy-induced neutropenia is a common cause of treatment-induced immune suppression. In the present study, the effect of a specific nutritional combination (SNC) on bacterial translocation was studied in a model of chemotherapy-induced neutropenia in C3H/HeN mice colonized with Pseudomonas aeruginosa PAO-1. Dietary intervention started after stable colonization with P. aeruginosa to compare the SNC containing high protein, l-leucine, fish oil, and specific oligosaccharides to an isoenergetic control diet. After 3 wk, the mice were treated with cyclophosphamide to induce neutropenia. This rendered the mice susceptible to Pseudomonas translocation, which was quantified 5 d later. Intervention with the SNC resulted in a reduced incidence and intensity of bacterial translocation to the liver (P < 0.05) and a similar trend in the lungs (P ≤ 0.057). In addition, the SNC reduced the fecal pH (P < 0.05) and decreased P. aeruginosa counts in fecal samples (P < 0.05). Moreover, plasma concentrations of proinflammatory cytokines were correlated with the reduced bacterial translocation to the liver (ρ > 0.78; P < 0.001). In conclusion, dietary intervention with the SNC significantly reduced the incidence and severity of P. aeruginosa translocation in a mouse model of chemotherapy-induced immune suppression. Several mechanisms might have played a role, including the modulation of the intestinal microbiota, an improved gut barrier function, immune function, and a reduced inflammatory state. These results suggest an opportunity to develop new applications in cancer patients, with the aim to reduce infectious and other complications.
authors.affiliation: Nutricia Advanced Medical Nutrition, Danone Research, Centre for Specialised Nutrition, Wageningen, The Netherlands 6704 PH. joyce.faber@danone.com
authors.forename: Joyce
authors.initials: J
authors.lastname: Faber
authors.forename: Kees
authors.initials: K
authors.lastname: van Limpt
authors.forename: Diane
authors.initials: D
authors.lastname: Kegler
authors.forename: Yvette
authors.initials: Y
authors.lastname: Luiking
authors.forename: Johan
authors.initials: J
authors.lastname: Garssen
authors.forename: Ardy
authors.initials: A
authors.lastname: van Helvoort
authors.forename: Arjan Paul
authors.initials: AP
authors.lastname: Vos
authors.forename: Jan
authors.initials: J
authors.lastname: Knol
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D018988:Bacterial Translocation; D003520:Cyclophosphamide / Q000633:toxicity; D016207:Cytokines / Q000097:blood; D004044:Dietary Proteins / Q000008:administration & dosage; D019587:Dietary Supplements; D015232:Dinoprostone / Q000097:blood; D004195:Disease Models, Animal; D005243:Feces / Q000382:microbiology; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage; D006863:Hydrogen-Ion Concentration; D007930:Leucine / Q000008:administration & dosage; D051379:Mice; D008809:Mice, Inbred C3H; D009503:Neutropenia / Q000139:chemically induced / Q000178:diet therapy* / Q000276:immunology / Q000382:microbiology; D009844:Oligosaccharides / Q000008:administration & dosage; D011552:Pseudomonas Infections / Q000178:diet therapy / Q000382:microbiology / Q000517:prevention & control; D011550:Pseudomonas aeruginosa / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D004044:Dietary Proteins; D005395:Fish Oils; D009844:Oligosaccharides; D003520:Cyclophosphamide; D007930:Leucine; D015232:Dinoprostone