Bovine colostrum modulates myeloablative chemotherapy-induced gut toxicity in piglets
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Bovine colostrum modulates myeloablative chemotherapy-induced gut toxicity in piglets. / Pontoppidan, Peter Erik Lotko; Shen, René Liang; Cilieborg, Malene Skovsted; Jiang, Pingping; Kissow, Hannelouise; Petersen, Bodil L.; Thymann, Thomas; Heilmann, Carsten; Muller, Klaus; Sangild, Per Torp.
In: Journal of Nutrition, Vol. 145, No. 7, 07.2015, p. 1472-1480.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Bovine colostrum modulates myeloablative chemotherapy-induced gut toxicity in piglets
AU - Pontoppidan, Peter Erik Lotko
AU - Shen, René Liang
AU - Cilieborg, Malene Skovsted
AU - Jiang, Pingping
AU - Kissow, Hannelouise
AU - Petersen, Bodil L.
AU - Thymann, Thomas
AU - Heilmann, Carsten
AU - Muller, Klaus
AU - Sangild, Per Torp
N1 - © 2015 American Society for Nutrition.
PY - 2015/7
Y1 - 2015/7
N2 - BACKGROUND: Intensive chemotherapy frequently results in gut toxicity, indicated by oral and intestinal mucositis, resulting in poor treatment outcomes and increased mortality. There are no effective preventive strategies against gut toxicity and the role of diet is unknown.OBJECTIVE: We hypothesized that the severity of chemotherapy-induced gut toxicity in early life is diet-dependent, and that intake of bovine colostrum (BC) provides better gut protection than an artificial milk replacer (MR).METHODS: A total of 37 3-d-old pigs received for 6 d either intravenous saline control or myeloablative treatment with busulfan and cyclophosphamide, and were fed either BC or MR, resulting in the following 4 treatments (n = 8-10/group): bovine colostrum plus saline control (Ctr-BC), milk replacer plus saline control (Ctr-MR), bovine colostrum plus busulfan and cyclophosphamide chemotherapy (BUCY-BC), and milk replacer plus busulfan and cyclophosphamide chemotherapy (BUCY-MR). The gut was collected for analysis 11 d after the start of chemotherapy.RESULTS: Relative to the control groups, both busulfan and cyclophosphamide chemotherapy (BUCY) groups showed signs of gut toxicity, with oral ulcers, reduced intestinal dimensions, and hematologic toxicity. Diet type did not affect mucosal structure on day 11, but BUCY-BC pigs had less vomiting than BUCY-MR pigs (1 of 10 vs. 10 of 10, P < 0.05). Markers of intestinal function were higher (up to 20-fold greater galactose absorption and 2-3-fold greater brush border enzyme activity, all P < 0.05), and tissue inflammatory cytokine concentrations and serum liver enzyme values were lower in BUCY-BC than in BUCY-MR pigs (30-50% reductions in interleukin 6 and 8, aminotransferase, and bilirubin concentrations, P < 0.05). Gut colonization was not significantly affected except that BUCY pigs had lower microbial diversity with a higher abundance of Lactobacilli.CONCLUSION: BC may reduce gut toxicity during myeloablative chemotherapy in piglets by preserving intestinal function and reducing inflammation. Whether similar effects occur in children remains to be tested.
AB - BACKGROUND: Intensive chemotherapy frequently results in gut toxicity, indicated by oral and intestinal mucositis, resulting in poor treatment outcomes and increased mortality. There are no effective preventive strategies against gut toxicity and the role of diet is unknown.OBJECTIVE: We hypothesized that the severity of chemotherapy-induced gut toxicity in early life is diet-dependent, and that intake of bovine colostrum (BC) provides better gut protection than an artificial milk replacer (MR).METHODS: A total of 37 3-d-old pigs received for 6 d either intravenous saline control or myeloablative treatment with busulfan and cyclophosphamide, and were fed either BC or MR, resulting in the following 4 treatments (n = 8-10/group): bovine colostrum plus saline control (Ctr-BC), milk replacer plus saline control (Ctr-MR), bovine colostrum plus busulfan and cyclophosphamide chemotherapy (BUCY-BC), and milk replacer plus busulfan and cyclophosphamide chemotherapy (BUCY-MR). The gut was collected for analysis 11 d after the start of chemotherapy.RESULTS: Relative to the control groups, both busulfan and cyclophosphamide chemotherapy (BUCY) groups showed signs of gut toxicity, with oral ulcers, reduced intestinal dimensions, and hematologic toxicity. Diet type did not affect mucosal structure on day 11, but BUCY-BC pigs had less vomiting than BUCY-MR pigs (1 of 10 vs. 10 of 10, P < 0.05). Markers of intestinal function were higher (up to 20-fold greater galactose absorption and 2-3-fold greater brush border enzyme activity, all P < 0.05), and tissue inflammatory cytokine concentrations and serum liver enzyme values were lower in BUCY-BC than in BUCY-MR pigs (30-50% reductions in interleukin 6 and 8, aminotransferase, and bilirubin concentrations, P < 0.05). Gut colonization was not significantly affected except that BUCY pigs had lower microbial diversity with a higher abundance of Lactobacilli.CONCLUSION: BC may reduce gut toxicity during myeloablative chemotherapy in piglets by preserving intestinal function and reducing inflammation. Whether similar effects occur in children remains to be tested.
KW - Animals
KW - Animals, Newborn
KW - Bilirubin
KW - Busulfan
KW - Cattle
KW - Citrulline
KW - Colostrum
KW - Cyclophosphamide
KW - Diet
KW - Endpoint Determination
KW - Interleukin-6
KW - Interleukin-8
KW - Intestinal Mucosa
KW - Intestines
KW - Microbiota
KW - Myeloablative Agonists
KW - Swine
KW - Transaminases
U2 - 10.3945/jn.114.203430
DO - 10.3945/jn.114.203430
M3 - Journal article
C2 - 26019247
VL - 145
SP - 1472
EP - 1480
JO - Journal of Nutrition
JF - Journal of Nutrition
SN - 0022-3166
IS - 7
ER -
ID: 160671250