A human, double-blind, placebo-controlled, crossover trial of prebiotic, probiotic, and synbiotic supplementation: effects on luminal, inflammatory, epigenetic, and epithelial biomarkers of colorectal cancer.
BACKGROUND
Diet is an important factor in colorectal carcinogenesis; thus, dietary supplements may have a role in colorectal cancer prevention.


OBJECTIVE
The objective was to establish the relative luminal, epithelial, and epigenetic consequences of prebiotic, probiotic, and synbiotic dietary supplementation in humans.


METHODS
This was a randomized, double-blind, placebo-controlled, 4-wk crossover trial of resistant starch and Bifidobacterium lactis, either alone or as a combined synbiotic preparation, in 20 human volunteers. Rectal biopsy, feces, and serum samples were collected. The rectal mucosal endpoints were DNA methylation at 16 CpG island loci and LINE-1, epithelial proliferation (Ki67 immunohistochemistry), and crypt cellularity. The fecal endpoints were short-chain fatty acid concentrations, pH, ammonia, and microbiological profiles (by denaturing gradient gel electrophoresis and sequencing). Serum endpoints were a panel of cytokines and high-sensitivity C-reactive protein.


RESULTS
Seventeen subjects completed the entire study. The synbiotic intervention fostered a significantly different fecal stream bacterial community than did either the prebiotic (P = 0.032) or the probiotic (P = 0.001) intervention alone, in part because of a greater proportion of patients harboring fecal Lachnospiraceae spp. These changes developed in the absence of any significant differences in fecal chemistry. There were no differences in epithelial kinetics.


CONCLUSIONS
This synbiotic supplementation with B. lactis and resistant starch, in the doses used, induced unique changes in fecal microflora but did not significantly alter any other fecal, serum, or epithelial variables. This trial was registered in the Australian New Zealand Clinical Trials Registry at www.anzctr.org.au as ACTRN012606000115538.
Worthley
Daniel L
DL
Royal Brisbane and Women's Hospital Research Foundation, Clinical Research Centre, Brisbane, Australia. daniel.worthley@uqconnect.edu.au
Le Leu
Richard K
RK
Whitehall
Vicki L
VL
Conlon
Michael
M
Christophersen
Claus
C
Belobrajdic
Damien
D
Mallitt
Kylie-Ann
KA
Hu
Ying
Y
Irahara
Natsumi
N
Ogino
Shuji
S
Leggett
Barbara A
BA
Young
Graeme P
GP
D000368:Aged; D000688:Amylose; D001419:Bacteria / Q000235:genetics / Q000302:isolation & purification*; D001644:Bifidobacterium; D015415:Biomarkers / Q000032:analysis; D015179:Colorectal Neoplasms / Q000382:microbiology* / Q000517:prevention & control; D018592:Cross-Over Studies; D019175:DNA Methylation; D019587:Dietary Supplements; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D044127:Epigenesis, Genetic; D004848:Epithelium / Q000382:microbiology; D005232:Fatty Acids, Volatile / Q000032:analysis; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D006801:Humans; D007249:Inflammation; D007413:Intestinal Mucosa / Q000382:microbiology; D008875:Middle Aged; D019936:Probiotics / Q000008:administration & dosage*; D013213:Starch / Q000008:administration & dosage / Q000494:pharmacology
D015415:Biomarkers; D005232:Fatty Acids, Volatile; D013213:Starch; D000688:Amylose