Dietary nucleic acid and intestinal microbiota synergistically promote a shift in the Th1/Th2 balance toward Th1-skewed immunity.
BACKGROUND
Intestinal microbiota are known to play an important role in the establishment of oral tolerance, thereby protecting the organism from food allergies. Dietary intake of nucleic acid (NA) is also reported to have such an anti-allergic effect; however, one unsolved question is whether or not dietary NA would act through a process of toll-like receptor 9 signaling activated by DNA containing a CpG motif, a well-known sequence leading to immunostimulatory activity. In this study, we focused on the question of whether the addition of dietary NA lacking CpG motifs would allow continued modulation of the Th1/Th2 balance.


METHODS
Germ free (GF) and Bifidobacterium-infantis-monoassociated BALB/c mice were maintained on either an NA-free casein diet or on an NA-supplemented casein diet for 4 weeks. Thereafter, both the in vivo anti-casein antibody levels and in vitro splenocyte cytokine secretion pattern were evaluated.


RESULTS
Feeding with a casein diet elicited a substantial increase in the serum anti-casein-specific IgG1, IgG2a, and IgE levels of GF mice fed the NA free-diet. The in vitro cytokine production profile showed that enhanced IL-4 production in the GF mice fed the NA free-diet was markedly reduced by the supplementation with dietary NA in both the GF and B.-infantis-monoassociated mice. In addition, IFN-gamma secretion increased in the B.-infantis-reconstituted mice fed the diet containing NA.


CONCLUSIONS
These results suggest that dietary intake of NA devoid of CpG motifs may prevent the development of allergies via acceleration of Th1-dominant immunity.
Sudo
Nobuyuki
N
Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. sudo@hcam.med.kyushu-u.ac.jp
Aiba
Yuji
Y
Oyama
Naomi
N
Yu
Xiao-Nian
XN
Matsunaga
Masaji
M
Koga
Yasuhiro
Y
Kubo
Chiharu
C
D000818:Animals; D039941:Bifidobacteriales Infections / Q000276:immunology; D001644:Bifidobacterium / Q000276:immunology; D002364:Caseins / Q000276:immunology; D018899:CpG Islands / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004032:Diet; D005512:Food Hypersensitivity; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007422:Intestines / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009696:Nucleic Acids / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D002364:Caseins; D016207:Cytokines; D007074:Immunoglobulin G; D009696:Nucleic Acids; D007073:Immunoglobulin E