2,4-Dinitrofluorobenzene-Induced Contact Hypersensitivity Response in NC/Nga Mice Fed Fructo-Oligosaccharide

Abstract

Summary Strategies to manipulate gut microbiota in infancy have been considered to prevent the development of allergic diseases later in life. We previously demonstrated that maternal dietary supplementation with fructo-oligosaccharide (FOS) during pregnancy and lactation modulated the composition of gut microbiota and diminished the severity of spontaneously developing atopic dermatitis-like skin lesions in the offspring of NC/Nga mice. The present study tested whether dietary FOS affects contact hypersensitivity (CHS), another model for allergic skin disease, in NC/Nga mice. In experiment 1, 5-wk-old female NC/Nga mice were fed diets either with or without FOS supplementation for 3 wk and then received 2,4-dinitrofluorobenzene (DNFB) on the ear auricle 5 times at 7-d intervals. FOS supplementation reduced CHS response as demonstrated by ear swelling. Quantitative RT-PCR analysis showed that mRNA levels for interleukin (IL)-10, IL-12p40, and IL-17 in the lesional ear skin were significantly lower in mice fed FOS. In experiment 2, female NC/Nga mice were fed diets either with or without FOS during pregnancy and lactation. After weaning, offspring were fed the diets supplemented with or without FOS. Three weeks after weaning, offspring received DNFB on the ear auricle 4 times at 7-d intervals. Although FOS supplementation after weaning reduced ear swelling, maternal FOS consumption was ineffective in offspring. The present data suggest that dietary FOS reduces CHS while maternal FOS consumption is ineffective in offspring of DNFB-treated NC/Nga mice. Key Words fructo-oligosaccharide, 2,4-dinitrofluorobenzene, contact hypersensitivity, gut microbiota, NC/Nga mice Because gut microbiota early in life profoundly influences later immune responses ( 1-4 ), strategies to manipulate the microbiota in infancy have been considered in preventing the onset of allergic diseases. In fact, clinical trials showed that maternal administration of Lactobacillus rhamnosus GG (i.e., probiotics) during pregnancy and lactation was beneficial in preventing the development of atopic dermatitis (AD) in at-risk children during the first 4 y of life ( 5 , 6 ). Likewise, animal experiments showed that dietary supplementation with heat-killed L. rhamnosus GG in NC/Nga mice during pregnancy and lactation suppressed the spontaneous development of AD-like skin lesions in offspring ( 7 ). In addition, administration of L. rhamnosus GG in female BALB/c mice during pregnancy and lactation suppressed the ovalbumin-induced allergic airway inflammation in their offspring ( 8 ). Furthermore, administration of Lactobacillus johnsonii NCC533 in NC/Nga mice around the weaning period (i.e., 20 to 22 d of age) prevented the development of allergic skin lesions induced by topical application of mite antigen from 6 wk of age ( 9 , 10 ).Because indigestible oligosaccharides (i.e., prebiotics) modulate the composition of gut microbiota, administration of indigestible oligosaccharides during infancy could be also expected to be effective in preventing the devel...

Non‐digestible oligosaccharides modulate intestinal immune activation and suppress cow's milk allergic symptoms

“…The single components were used in the same amount as present in the mixture which resembles the natural composition of neutral vs. acidic oligosaccharides present in human milk. However, increased dosages of the single components may be beneficial as was shown, for example for FOS (25)(26)(27). Although the mixtures of oligosaccharides were effective in allergy prevention, which is in line with recent studies in human and mice (4,8,(10)(11)(12)(13), they lacked effectiveness in the used treatment protocol.…”

The Interplay Between Fiber and the Intestinal Microbiome in the Inflammatory Response

“…Similar FOS supplementation also reduced the ovalbumininduced allergic peritonitis (105) and allergic asthma (106) in mice. Mice receiving FOS (5% in diet) showed less 2,4-dinitrofluorobenzene-induced contact sensitivity and less increase in plasma inflammatory markers (107,108). The same amount of FOS supplementation also reduced spontaneous skin lesions and inflammation-related cytokines in NC/Nga mice (109).…”

Broad spectrum antibiotic enrofloxacin modulates contact sensitivity through gut microbiota in a murine model

“…The influence of microbiota on CS response is not well explored. A few studies suggest that the proliferation of Bifidobacterium pseudolongum in the intestinal tract could be partially responsible for the reduction of 2,4-dinitro-1-fluorobenzeneinduced CD8 Tc1-mediated CS response in mice, 34,35 and oral administration of the probiotic Lactobacillus casei alleviates CD8 Tc1-mediated CS to 2,4-dinitro-1-fluorobenzene. 36 Currently there are no studies, however, investigating the role of microbiota in CD4 1 T H 1-mediated CS responses.…”