Maternal microbiota Bifidobacterium promotes placental vascularization, nutrient transport and fetal growth in mice

The gut microbiota plays a central role in regulating host metabolism. However, while substantial progress has been made in discerning how the microbiota influences host functions post birth and beyond, little has been carried out into understanding how key members of the maternal gut microbiota can influence feto-placental growth. Here, using germ-free and specific-pathogen-free mice, we demonstrate that the bacterium Bifidobacterium breve UCC2003 modulates maternal body adaptations, placental vasculature growth and nutrient transporter capacity, with implications for fetal metabolism and growth. The effects of B. breve UCC2003 on feto-placental growth are mediated, in part, by changes in the maternal and placental metabolome (i.e. acetate and carnitine). Analysis of placental vascular bed confirmed that Bifidobacterium improves fetal capillary elongation via changes in Igf2P0, Dlk1 and Mapk14 expression. Additionally, B. breve UCC2003, acting through Slc2a1 and Fatp3-4 transporters, was shown to restore fetal glycaemia and improve fetal growth in association with changes in the fetal hepatic transcriptome. This study provides knowledge towards a novel and safe therapeutic strategy for treating pregnancy disorders via modulation of the maternal gut microbiota.

Complementary α-arrestin-ubiquitin ligase complexes control nutrient transporter endocytosis in response to amino acids

How cells adjust nutrient transport across their membranes is incompletely understood. Previously, we have shown that S. cerevisiae broadly re-configures the nutrient transporters at the plasma membrane in response to amino acid availability, through endocytosis of sugar- and amino acid transporters (AATs) (Müller et al., 2015). A genome-wide screen now revealed that the selective endocytosis of four AATs during starvation required the α-arrestin family protein Art2/Ecm21, an adaptor for the ubiquitin ligase Rsp5, and its induction through the general amino acid control pathway. Art2 uses a basic patch to recognize C-terminal acidic sorting motifs in AATs and thereby instructs Rsp5 to ubiquitinate proximal lysine residues. When amino acids are in excess, Rsp5 instead uses TORC1-activated Art1 to detect N-terminal acidic sorting motifs within the same AATs, which initiates exclusive substrate-induced endocytosis. Thus, amino acid excess or starvation activate complementary α-arrestin-Rsp5-complexes to control selective endocytosis and adapt nutrient acquisition.

Effect of phytase on nutrient digestibility and expression of intestinal tight junction and nutrient transporter genes in pigs

The study was conducted to determine the effects of high levels of phytase on growth performance, nutrient digestibility, phytate breakdown, and expression of mucosal tight junction and nutrient transporter genes in weanling pigs. A total of 128 barrows were penned in groups of four and used in a randomized completely block design and assigned to four treatments for a 28-d study. A two-phase feeding was implemented (phase 1: day 1 to 14; phase 2: day 15 to 28). The diets differed in dietary calcium (Ca) and phosphorus (P) levels (positive control [PC]: 8.1 to 7.1 g/kg Ca and 6.5 to 6.8 g/kg P; negative control [NC]: 6.6 to 5.5 g/kg Ca and 5.6 to 5.3 g/kg P) from phase 1 to phase 2, respectively. NC diets were supplemented with phytase at 0 (NC), 1,500 (NC + 1,500), or 3,000 (NC + 3,000) phytase units (FTU)/kg. Blood was collected after fasting (day 27) or feeding (day 28) for the measurement of plasma inositol concentrations. On day 28, two pigs per pen were euthanized. Duodenal–jejunal and ileal digesta samples and feces were collected to determine inositol phosphates (InsP3-6) concentrations. Phytase supplementation increased the body weight on days 14 and 28 (P < 0.05). Average daily gain and feed efficiency compared with NC were increased by phytase with the majority of its effect in phase 1 (P < 0.05). The apparent ileal digestibility and apparent total tract digestibility of P were increased in piglets fed phytase-supplemented diets (P < 0.01) compared with NC piglets. Disappearance of InsP6 and total InsP3-6 up to the duodenum–jejunum, ileum, and in feces was increased by both phytase application rates (P < 0.01). Plasma concentrations of myo-inositol were higher (P < 0.001) in the phytase-supplemented diets than PC and NC diets, irrespective of whether pigs were fed or fasted. Expression of claudin 3 was higher in pigs fed both phytase-supplemented diets in the duodenum and jejunum compared with PC and NC. Mucin 2 expression was lower in the ileum of NC + 3,000 fed piglets compared with PC (P < 0.05), whereas expression of GLUT2 (solute carrier family 2-facilitated glucose transporter member 2) was increased (P < 0.05) by the NC + 3,000 treatment in all sections. In summary, high phytase supplementation increased the growth performance of nursery pigs. The increased expression of GLUT2 by phytase may indicate an upregulation of glucose absorption from the intestine by phytase.

Paternal High Fat Diet and Exercise Regulate Sperm miRNA to Alter Placental Inflammation and Nutrient Transporter Expression in a Sex-Dependent Manner

Objectives We have shown that male offspring (F1) of fathers (F0) fed a high fat (HF) diet and exercised had greater skeletal muscle insulin signaling and reduced T2DM risk compared to fathers fed HF diet and remain sedentary. The current study extends this work by hypothesizing that F0 HF diet and exercise regulate F1 T2DM risk by early alterations in epigenetics of placental tissue growth via changes in sperm miRNA expression. Methods To test these hypotheses, three-week old male C57BL/6 mice were fed a normal-fat (NF) diet (16% fat) or a HF diet (45% fat) and assigned to either voluntary wheel running exercise or cage activity for 3 months prior to mating with NF diet fed dams. F0 sperm and placental tissue samples were collected to determine changes in placental and fetal weights, placental gene expression, and F0 sperm miRNA expression. Results F0 sperm miRNA 193b expression was decreased while miRNA 204 was increased by paternal exercise. Protein expression of di-methylated histone 3 lysine 9 was decreased with F0 HF diet. Placental and fetal tissue weights were decreased by F0 HF diet in F1 males while no changes in the F1 females. Placental proinflammatory cytokine mRNA expression, including IL-1 beta and TNF-alpha, was reduced by paternal exercise while nutrient transporter mRNA expression was decreased by paternal HF diet only in the placentae of F1 females. Treatment of primary placental cell with miRNA 193 inhibited TNF-alpha mRNA expression. In addition, treatment of the same cells with TNF-alpha increased SLC6a19. Moreover, paternal exercise increased body weight at weaning in a female offspring. Conclusions These results demonstrate that placental tissue weight, placental nutrient transporter gene expression and fetal weights are altered by paternal exercise while placental inflammatory gene expression are influenced by paternal exercise in offspring in a sex-specific manner. Funding Sources This work was supported by USDA ARS Project #3062–51,000-054–00D.