Diet- and Genetically-Induced Obesity Differentially Affect the Fecal Microbiome and Metabolome in Apc1638N Mice.
Obesity is a risk factor for colorectal cancer (CRC), and alterations in the colonic microbiome and metabolome may be mechanistically involved in this relationship. The relative contribution of diet and obesity per se are unclear. We compared the effect of diet- and genetically-induced obesity on the intestinal microbiome and metabolome in a mouse model of CRC. Apc1638N mice were made obese by either high fat (HF) feeding or the presence of the Leprdb/db (DbDb) mutation. Intestinal tumors were quantified and stool microbiome and metabolome were profiled. Genetic obesity, and to a lesser extent HF feeding, promoted intestinal tumorigenesis. Each induced distinct microbial patterns: taxa enriched in HF were mostly Firmicutes (6 of 8) while those enriched in DbDb were split between Firmicutes (7 of 12) and Proteobacteria (5 of 12). Parabecteroides distasonis was lower in tumor-bearing mice and its abundance was inversely associated with colonic Il1b production (p<0.05). HF and genetic obesity altered the abundance of 49 and 40 fecal metabolites respectively, with 5 in common. Of these 5, adenosine was also lower in obese and in tumor-bearing mice (p<0.05) and its concentration was inversely associated with colonic Il1b and Tnf production (p<0.05). HF and genetic obesity differentially alter the intestinal microbiome and metabolome. A depletion of adenosine and P.distasonis in tumor-bearing mice could play a mechanistic role in tumor formation. Adenosine and P. distasonis have previously been shown to be anti-inflammatory in the colon and we postulate their reduction could promote tumorigenesis by de-repressing inflammation.
Cancer Cluster, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America; Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, United States of America.
Anna C
AC
Pfalzer
Cancer Cluster, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America; Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, United States of America.
Paula-Dene C
PD
Nesbeth
Cancer Cluster, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America; Agricultural Research Service, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America.
Laurence D
LD
Parnell
Neuroscience Department, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
Lakshmanan K
LK
Iyer
Cancer Cluster, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America; Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, United States of America; Department of Nutrition, University of Massachusetts, Amherst, Massachusetts, United States of America.
Zhenhua
Z
Liu
Cancer Cluster, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America; Phoenix Laboratory, Tufts Medical Center, Boston, Massachusetts, United States of America.
Anne V
AV
Kane
Cancer Cluster, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America; Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, United States of America.
C-Y Oliver
CY
Chen
Genomics Core, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
Albert K
AK
Tai
Cancer Cluster, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America.
Thomas A
TA
Bowman
Cancer Cluster, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America; Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, United States of America.
Martin S
MS
Obin
Cancer Cluster, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America; Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, United States of America.
Joel B
JB
Mason
Cancer Cluster, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America; Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, United States of America.
Andrew S
AS
Greenberg
Cancer Cluster, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America; CHA University School of Medicine, Seoul, South Korea.
Sang-Woon
SW
Choi
Cancer Cluster, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America; Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, United States of America.
Jacob
J
Selhub
Cancer Cluster, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America; Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, United States of America.
Ligi
L
Paul
Cancer Cluster, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America; Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, United States of America.
Jimmy W
JW
Crott
D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D005243:Feces / Q000737:chemistry* / Q000382:microbiology*; D005260:Female; D007414:Intestinal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D008297:Male; D055442:Metabolome / Q000187:drug effects / Q000235:genetics; D051379:Mice; D064307:Microbiota / Q000187:drug effects / Q000235:genetics; D009154:Mutation; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D054411:Receptors, Leptin / Q000172:deficiency / Q000235:genetics*
D054411:Receptors, Leptin