Effect of maternal curcumin supplementation on intestinal damage and the gut microbiota in male mice offspring with intra-uterine growth retardation

Purpose The present study investigated whether maternal curcumin supplementation might protect against intra-uterine growth retardation (IUGR) induced intestinal damage and modulate gut microbiota in male mice offspring. Methods In total, 36 C57BL/6 mice (24 females and 12 males, 6-8 weeks old) were randomly divided into three groups based on the diet before and throughout pregnancy and lactation: (1) normal protein (19%), (2) low protein (8%), and (3) low protein (8%) + 600 mg kg(-1) curcumin. Offspring were administered a control diet until postnatal day 35. Results Maternal curcumin supplementation could normalize the maternal protein deficiency-induced decrease in jejunal SOD activity (NP = 200.40 +/- 10.58 U/mg protein; LP = 153.30 +/- 5.51 U/mg protein; LPC = 185.40 +/- 9.52 U/mg protein; P < 0.05) and T-AOC content (NP = 138.90 +/- 17.51 U/mg protein; LP = 84.53 +/- 5.42 U/mg protein; LPC = 99.73 +/- 12.88 U/mg protein; P < 0.05) in the mice offspring. Maternal curcumin supplementation increased the maternal low protein diet-induced decline in the ratio of villus height-to-crypt depth (NP = 2.23 +/- 0.19; LP = 1.90 +/- 0.06; LPC = 2.56 +/- 0.20; P < 0.05), the number of goblet cells (NP = 12.72 +/- 1.16; LP = 7.04 +/- 0.53; LPC = 13.10 +/- 1.17; P < 0.05), and the ratio of PCNA-positive cells (NP = 13.59 +/- 1.13%; LP = 2.42 +/- 0.74%; LPC = 6.90 +/- 0.96%; P < 0.05). It also reversed the maternal protein deficiency-induced increase of the body weight (NP = 13.00 +/- 0.48 g; LP = 16.49 +/- 0.75 g; LPC = 10.65 +/- 1.12 g; P < 0.05), the serum glucose levels (NP = 5.32 +/- 0.28 mmol/L; LP = 6.82 +/- 0.33 mmol/L; LPC = 4.69 +/- 0.35 mmol/L; P < 0.05), and the jejunal apoptotic index (NP = 6.50 +/- 1.58%; LP = 10.65 +/- 0.75%; LPC = 5.24 +/- 0.71%; P < 0.05). Additionally, maternal curcumin supplementation enhanced the gene expression level of Nrf2 (NP = 1.00 +/- 0.12; LP = 0.73 +/- 0.10; LPC = 1.34 +/- 0.12; P < 0.05), Sod2 (NP = 1.00 +/- 0.04; LP = 0.85 +/- 0.04; LPC = 1.04 +/- 0.04; P < 0.05) and Ocln (NP = 1.00 +/- 0.09; LP = 0.94 +/- 0.10; LPC = 1.47 +/- 0.09; P < 0.05) in the jejunum. Furthermore, maternal curcumin supplementation normalized the relative abundance of Lactobacillus (NP = 31.56 +/- 6.19%; LP = 7.60 +/- 2.33%; LPC = 17.79 +/- 2.41%; P < 0.05) and Desulfovibrio (NP = 3.63 +/- 0.93%; LP = 20.73 +/- 3.96%; LPC = 13.96 +/- 4.23%; P < 0.05), and the ratio of Firmicutes/Bacteroidota (NP = 2.84 +/- 0.64; LP = 1.21 +/- 0.30; LPC = 1.79 +/- 0.15; P < 0.05). Moreover, Lactobacillus was positively correlated with the SOD activity, and it was negatively correlated with Il - 1 beta expression (P < 0.05). Desulfovibrio was negatively correlated with the SOD activity and the jejunal expression of Sod1, Bcl - 2, Card11, and Zo - 1 (P < 0.05). Conclusions Maternal curcumin supplementation could improve intestinal integrity, oxidative status, and gut microbiota in male mice offspring with IUGR.