ABSTRACT
BACKGROUND: Alteration of the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Epigallocatechin-3-gallate (EGCG), a major bioactive constituent of green tea, is known to be beneficial in IBD alleviation. However, it is unclear whether the gut microbiota exerts an effect when EGCG attenuates IBD. RESULTS: We first explored the effect of oral or rectal EGCG delivery on the DSS-induced murine colitis. Our results revealed that anti-inflammatory effect and colonic barrier integrity were enhanced by oral, but not rectal, EGCG. We observed a distinct EGCG-mediated alteration in the gut microbiome by increasing Akkermansia abundance and butyrate production. Next, we demonstrated that the EGCG pre-supplementation induced similar beneficial outcomes to oral EGCG administration. Prophylactic EGCG attenuated colitis and significantly enriched short-chain fatty acids (SCFAs)-producing bacteria such as Akkermansia and SCFAs production in DSS-induced mice. To validate these discoveries, we performed fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) to inoculate DSS-treated mice. Microbiota from EGCG-dosed mice alleviated the colitis over microbiota from control mice and SFF shown by superiorly anti-inflammatory effect and colonic barrier integrity, and also enriched bacteria such as Akkermansia and SCFAs. Collectively, the attenuation of colitis by oral EGCG suggests an intimate involvement of SCFAs-producing bacteria Akkermansia, and SCFAs, which was further demonstrated by prophylaxis and FMT. CONCLUSIONS: This study provides the first data indicating that oral EGCG ameliorated the colonic inflammation in a gut microbiota-dependent manner. Our findings provide novel insights into EGCG-mediated remission of IBD and EGCG as a potential modulator for gut microbiota to prevent and treat IBD. Video Abstract.
Subject(s)
Colitis , Gastrointestinal Microbiome , Animals , Colitis/chemically induced , Colitis/drug therapy , Dextran Sulfate , Disease Models, Animal , Homeostasis , Mice , Mice, Inbred C57BL , Polyphenols/pharmacology , TeaABSTRACT
Within-litter birth weight variation in multiparous animals has become a big issue due to high incidence of low birth weight neonates, which gives rise to high preweaning mortality and morbidity. Foetus with various birth weights is the outcome of diverse embryos competence which is affected by oocyte quality. Glucosamine (GlcN) has been reported to be involved in oocyte maturation; however, its effect on pregnant outcomes remains unknown. The present study was conducted to investigate the effects of premating GlcN supplementation via drinking water on within-litter birth weight variation and its underlying mechanism. Fifty eight Sprague-Dawley female rats were randomly assigned to one of two groups with normal drinking water or drinking water supplemented with 0.5 mM GlcN from six to eight weeks old. Variation of within-litter birth weight in the GlcN group was 5.55%, significantly lower compared with 8.17% in the control group. Birth weight was significantly increased in the GlcN group (2.27 ± 0.06) compared with the control group (2.08 ± 0.04). Both absolute and relative weights of the ovary at the end of GlcN treatment were higher in the GlcN group than in the control group (P < 0.05). In the GlcN group, there were more successfully implanted blastocysts (13.38 ± 0.63 and 15.75 ± 0.59 in the control and treatment group, respectively) with more uniform distribution along the two uterine horns compared with the control group. Besides, gene expressions of Alk3 and Bmp2 were increased in the implantation sites, while IGF-1 and Mucin-1 were decreased significantly in rats administrated with GlcN. Maternal progesterone, estradiol, and IGF-1 concentrations on D 19.5 were significantly increased, while insulin and total cholesterol levels were significantly decreased in contrast with control dams. In summary, the administration of 0.5 mM GlcN solution before mating reduced within-litter birth weight variation, accompanied with increased fetal weight. Further investigation indicated that the improved outcome of pregnancy results at least partly from the increased ovary weights of the rats, the homogeneous embryo developmental competence, the enhanced receptivity of the uterine environment, and the adjusted maternal hormone levels.
Subject(s)
Birth Weight/drug effects , Dietary Supplements , Embryo Implantation/drug effects , Glucosamine/pharmacology , Animals , Female , Pregnancy , Rats , Rats, Sprague-DawleyABSTRACT
The high within-litter birth weight variation has become a big issue in multiparous animals. The present study was conducted to investigate the effects of leucine supplementation in premating diet on the reproductive performance, maternal antioxidative capability, and immune function in primiparous rats. Six-week-old female SD rats were assigned to basal diet or 0.6% leucine supplemented diet for two weeks. After mating during the eighth week of age, the rats were fed with regular gestation diet. Maternal blood samples were collected on the day before mating (day -1) and day 7 and day 20 of pregnancy, while ovaries and uteruses were obtained on day -1 and on day 7, respectively. The results indicate that, compared with control group, within-litter birth weight variation was significantly decreased, while birth weights were significantly increased in the leucine group (P < 0.01). Also, leucine improved the embryo distribution uniformity and the number of implantation sites in uterine. The ovarian gene expressions of LHR, CYP19A1, and VEGFA were upregulated, while Mucin-1 was decreased significantly (P < 0.05). Leucine also increased the maternal antioxidant capacity and immune function. Conclusively, leucine supplementation in premating diet could improve the reproductive performance, which could be attributed to the improved oxidative and immune status.