Role of iron in host-microbiota interaction and its effects on intestinal mucosal growth and immune plasticity in a piglet model.

Iron is an essential trace element for both the host and resident microbes in the gut. In this study, iron was administered orally and parenterally to anemic piglets to investigate the role of iron in host-microbiota interaction and its effects on intestinal mucosal growth and immune plasticity. We found that oral iron administration easily increased the abundance of Proteobacteria and Escherichia-Shigella, and decreased the abundance of Lactobacillus in the ileum. Furthermore, similar bacterial changes, namely an increase in Proteobacteria, Escherichia-Shigella, and Fusobacterium and a reduction in the Christensenellaceae_R-7_group, were observed in the colon of both iron-supplemented groups. Spearman's correlation analysis indicated that the changed Fusobacterium, Fusobacteria and Proteobacteria in the colon were positively correlated with hemoglobin, colon and spleen iron levels. Nevertheless, it was found that activated mTOR1 signaling, improved villous height and crypt depth in the ileum, enhanced immune communication, and increased protein expression of IL-22 and IL-10 in the colon of both iron-supplemented groups. In conclusion, the benefits of improved host iron outweigh the risks of altered gut microbiota for intestinal mucosal growth and immune regulation in treating iron deficiency anemia.

A parallel-group study of near-infrared spectroscopy-neurofeedback in children with attention deficit hyperactivity disorder.

The present study aimed to assess the efficacy of Near-infrared spectroscopy (NIRS) real-time neurofeedback (NF) vs. atomoxetine (AT) in children with attention deficit hyperactivity disorder (ADHD). A parallel-group study was conducted to enroll children with ADHD between 8 and 12 years of age. Participants were assigned into the NIRS group and AT group as their wish. Subjects in the NIRS group received 12 sessions of NF training within 6 weeks, and subjects in the AT group were given oral medication. Changes in Swanson, Nolan, and Pelham-V rating scales (SNAP-IV), and performance of Go/No-Go and N-back working memory tasks at week 3, 6 and 8 were evaluated. Forty-nine patients completed the study, including 18 ADHD in the NIRS group and 31 in the AT group. Total scores of SNAP-IV significantly decreased from baseline to week 3, week 6, and week 8 in both groups. Patients in the NIRS group showed significant lower scores on the inattention subscale of SNAP-IV at week 3 and week 6, compared to the AT group. NIRS group had a shorter reaction time during the Go/No-Go task at week 6 and fewer errors during 2-back than the AT group at week 3. The findings revealed that NIRS real-time NF is more efficacious relative to AT in improving behavioral performance, highlighting its potential role and advantages in treating patients with ADHD.

Electroacupuncture enhances resting-state functional connectivity between dorsal caudate and precuneus and decreases associated leptin levels in overweight/obese subjects.

Electroacupuncture (EA) is a safe and effective method for treating obesity. However, how it modulates reward-related brain activity/functional connectivity and gut hormones remains unclear. We employed resting-state functional magnetic resonance imaging (RS-fMRI) and resting-state functional connectivity (RSFC) to investigate EA induced changes in resting-state activity and RSFC in reward-related regions and its association with gut hormones in overweight/obese subjects who received real (n = 20) and Sham (n = 15) stimulation. Results showed reduced leptin levels was positively correlated with reduced body mass index (BMI) and negatively correlated with increased cognitive-control as measured with Three-Factor-Eating-Questionnaire (TFEQ). Significant time effects on RSFC between dorsal caudate (DC) and precuneus were due to significant increased RSFC strength in both EA and Sham groups. In addition, increased RSFC of DC-precuneus was negatively correlated with reduced BMI and leptin levels in the EA group. Mediation analysis showed that the relationship between increased DC-precuneus RSFC strength and reduced BMI was mediated by reduced leptin levels. These findings reflect the association between EA-induced brain reward-related RSFC and leptin levels, and decreased leptin levels mediated altered DC-precuneus RSFC strength and consequent weight-loss, suggesting the potential role of EA in reducing weight and appetite.

Distinct Basal Brain Functional Activity and Connectivity in the Emotional-Arousal Network and Thalamus in Patients With Functional Constipation Associated With Anxiety and/or Depressive Disorders.

OBJECTIVE: Functional constipation (FC) is a common gastrointestinal disorder. Anxiety and/or depressive disorders are common in patients with FC (FCAD). Brain dysfunction may play a role in FC, but the contribution of comorbid anxiety and/or depression in patients with FC is poorly understood. METHODS: Sixty-five FC patients and 42 healthy controls (HCs) were recruited, and a hierarchical clustering algorithm was used to classify FC patients into FCAD and patients without anxiety/depressive status (FCNAD) based on neuropsychological assessment. Resting-state functional magnetic resonance imaging measures including fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity were used to investigate brain functional differences. RESULTS: Thirty-seven patients were classified as FCAD, and 28 patients were classified as FCNAD; as compared with HC, both groups showed decreased activity (fALFF) in the perigenual anterior cingulate cortex (pACC), dorsomedial prefrontal cortex (DMPFC), and precuneus; enhanced precentral gyrus-thalamus connectivity and attenuated precuneus-thalamus connectivity in FCAD/FCNAD highlighted the thalamus as a critical connectivity node in the brain network (pFWE < .05). In comparison with FCNAD/HC, the FCAD group also had decreased fALFF in the orbitofrontal cortex (OFC) and thalamus, and increased OFC-hippocampus connectivity. In the FCNAD group, brain activities (pACC/DMPFC) and connection (precuneus-thalamus) had correlations only with symptoms; in the FCAD group, brain activities (OFC, pACC/DMPFC) and connectivities (OFC-hippocampus/precentral gyrus-thalamus) showed correlations with both constipation symptoms and anxiety/depressive status ratings. Mediation analysis indicated that the relationship between abdominal distension and OFC activity was completely mediated by anxiety in FCAD. CONCLUSIONS: These findings provide evidence of differences in brain activity and functional connectivity between FCAD and FCNAD, potentially providing important clues for improving treatment strategies.

Effects of Iron Deficiency on Serum Metabolome, Hepatic Histology, and Function in Neonatal Piglets.

Few studies focused on the effects of iron on characterizing alterations of metabolic processes in neonatal piglets. In the present study, 16 neonatal piglets were randomly assigned to two groups. In the first group piglets were given an intramuscularly injection of iron dextran at 150 mg as a positive control (CON) and the second group were not supplemented with iron as a negative control for iron deficiency (ID). At day 8, iron status, serum biochemical parameters, serum metabolome, hepatic histology, and hepatic expression of genes for the metabolism were analyzed. Results indicated that piglets without iron supplementation had significantly reduced iron values and increased blood urea nitrogen concentrations at day 8 (p < 0.05). Analysis of serum metabolome revealed that concentrations of serum lysine, leucine, tyrosine, methionine, and cholesterol were significantly decreased while concentrations of 3-Methyldioxyindole, chenodeoxycholate acid, indoleacetic acid, icosadienoic acid, phenylpyruvic acid, pantothenic acid, ursocholic acid, and cholic acid were significantly increased in iron deficient piglets (p < 0.05). Furthermore, expressions of cyp7a1 and the urea cycle enzyme (ornithinetranscarbamoylase and argininosuccinate synthetase) were significantly increased in iron deficient pigs (p < 0.05). The present experimental results indicated that neonatal piglets without iron supplementation drop to borderline anemia within 8 days after birth. Iron deficiency led to a series of metabolic changes involved in tyrosine metabolism, phenylalanine metabolism, bile secretion, primary bile acid biosynthesis, steroid biosynthesis, and upregulated activities of the urea cycle enzymes in the liver of neonatal piglets, suggesting early effects on metabolic health of neonatal piglets.

Dietary supplementation with N-carbamylglycinate (CGly) improved feed source proline absorption and reproductive performance in sows.

Nutrient requirements are increased in the late-gestation period due to the faster growth of the foetal-placental unit and maternal erythrocyte mass. Glycine, proline and arginine are important amino acids that could improve foetal growth and development. The present study aims to investigate the effects of a derivative of glycine (N-carbamylglycinate, CGly) on the amino acid profiles and reproductive performances of late gestation sows. Thirty-two multiparous gestating sows (∼d 80) were selected, and randomly assigned into two groups: (1) control and (2) treatment (CGly, 800 mg kg-1) from day 85 of gestation to parturition. The serum amino acid profiles at day 110 of gestation and reproductive performance were investigated. The results showed that dietary supplementation of CGly in the late gestation period significantly improved the levels of glycine (p < 0.05) and proline (p < 0.01) in the serum of the perinatal sows, and thereafter improved the litter birth weights (p < 0.05) and number born alive (p < 0.1). Based on the in vitro studies, the improvement of proline levels is probably due to the induced expression of SLC6A20 and SLC38A2. Further studies should focus on the details of amino acid absorption, especially the competitive and cooperative absorption processes for different amino acids and derivatives.

Acute and long-term effects of electroacupuncture alter frontal and insular cortex activity and functional connectivity during resting state.

Electroacupuncture (EA) is a safe method for treating obesity; however, its underlying neural mechanisms remain unclear. We employed resting-state-functional-magnetic-resonance-imaging (RS-fMRI) and amplitude-of-low-frequency-fluctuation (ALFF) to investigate acute/long-term effects of EA on brain activity and resting-state-functional-connectivity (RSFC) in overweight/obesity subjects who received real/Sham stimulation. For acute effects, 26 and 19 overweight/obesity subjects were included in EA and Sham groups respectively. There were significant time effects on ALFF in the right insula (INS) and left dorsolateral-prefrontal-cortex (DLPFC) due to decreases/increases in INS/DLPFC in both groups. There were weaker positive RSFC between INS and supplementary-motor-area (SMA)/right DLPFC and weaker negative RSFC between INS and precuneus (PCUN); stronger negative RSFC between DLPFC and dorsomedial-prefrontal-cortex (DMPFC) in both groups. For long-term study, body-mass-index (BMI) had significant reduction in EA (n = 17) and Sham (15) groups; EA had higher BMI reduction than in Sham. There were significant time effects on ALFF in right ventrolateral-prefrontal-cortex (VLPFC) due to significant increases in EA group, and stronger positive RSFC between VLPFC and orbitofrontal-cortex and negative RSFC between VLPFC and left thalamus (THA) in both groups after long-term treatment. These findings suggest that changes in resting-activity and RSFC implicated in inhibitory-control, gastric-motility and satiety-control are associated with EA-induced weight-loss.

Comparison of Oral and Parenteral Iron Administration on Iron Homeostasis, Oxidative and Immune Status in Anemic Neonatal Pigs.

The present study was to evaluate the consequences of iron status across oral and parenteral iron administrations in prevention of iron deficiency anemia. A total of 24 one-day-old male neonatal piglets were allocated into three groups given non-iron supplementation (NON), intramuscular iron dextran injection (FeDex), and oral administration of ferrous glycine chelate (FeGly), respectively. At day 8, no significant differences in final body weight, average weight gain, and tissue coefficients were observed among three groups (P > 0.05). Both oral FeGly and FeDex injection significantly increased serum iron, ferritin, hemoglobin, and tissue iron deposition (P < 0.05). However, FeDex-injected supplementation resulted in rapidly rising hepcidin levels and hepatic iron deposition (P < 0.05). In addition, compared to parenteral iron supplementation, greater serum IgA level, SOD, and GSH-Px activities, lower expressions of IL-1ß and TNF-α in the liver, and lower expressions of IL-6 and TNF-α in the spleen were found in oral iron piglets (P < 0.05). According to our results, oral administration of ferrous glycine chelate improved iron homeostasis, and oxidative and immune status in anemic neonatal pigs.

Dietary supplement with nucleotides in the form of uridine monophosphate or uridine stimulate intestinal development and promote nucleotide transport in weaned piglets.

BACKGROUND: Nucleotides are key constituents of milk, where they are utilized in cell replication, although there are limited studies for weaned piglets. This study evaluated the effects of uridine monophosphate (UMP) with uridine (UR) feed supplementation on the intestinal development and nucleotide transport in weaned piglets. RESULTS: Supplementation with UMP significantly increased (P < 0.05) plasma glucose, and UR supplementation significantly reduced (0.05 < P < 0.10) the plasma total cholesterol (TC) of piglets when compared with that of the control group, although non-significant difference (P > 0.05) in growth performance was observed among three groups. Piglets fed supplementary UR exhibited greater (P < 0.05) crypt depth in the duodenum and ileum when compared with those in the supplementary UMP and control groups. Real-time quantitative polymerase chain reaction (RT-qPCR) results revealed that UR supplementation increased (P < 0.05) the relative mRNA levels of genes encoding the transmembrane proteins ZO-1 and occludin in the duodenum mucosa, and ZO-1 in the jejunum mucosa (P < 0.05). Similarly, UR supplementation increased (P < 0.05) expression of solute carriers SLC28A1 and SLC29A1 in the duodenum mucosa. Conversely, claudin-1 expression in the duodenum mucosa was inhibited (P < 0.05) by dietary supplementation with UMP or UR. CONCLUSION: Collectively, our data indicated that dietary supplementation with UMP or UR was conducive to stimulating intestinal development and promoting nucleotide transport in weaned piglets. © 2019 Society of Chemical Industry.

Uridine/UMP metabolism and their function on the gut in segregated early weaned piglets.

Uridine monophosphate (UMP) is a major nucleotide analogue in mammalian milk and uridine (UR) is its gastro-intestinal metabolite in vivo. This study aims to investigate the functional effects of UMP and UR on the gut in vitro and in vivo. Twenty-one piglets were randomly allotted into three groups, the control group, UMP group and UR group, and orally administered UMP or UR for 10 days. Results showed that UMP and UR supplements improved the ADG of piglets, and decreased the diarrhea rate. UR increased the jejunum villus length/crypt depth ratio, Claudin-3 and E-cadherin expression, and the pyrimidine nucleotide metabolic enzymes including CMPK1, RRM2, UPRT, CTPS1 and CTPS2 in the duodenal mucosa. Both the UMP and UR decreased the expression of CAD and RRM2 at the jejunal mucosa. Moreover, UMP and UR increased the apoptosis ratio of intestinal epithelial cells in in vivo and in vitro experiments. Taken together, oral administration of UR and UMP could improve the small intestinal morphology, promote epithelial cell apoptosis and renewal of intestinal villus tips, and benefit intestinal development and health thus improving the growth performance and reducing the risk of diarrhea in early-weaned piglets.

Effect of Dietary Copper on Intestinal Microbiota and Antimicrobial Resistance Profiles of Escherichia coli in Weaned Piglets.

Copper is an essential microelement for animals, and not only it has been used as a feed additive at pharmacological doses in swine production to improve growth performance, but it also has an effect on intestinal microbes by enhancing host bacterial resistance. However, there are few reports on the effects of pharmacological doses of copper on intestinal microorganisms and the antimicrobial resistance profiles of pathogenic bacteria, such as Escherichia coli, in pigs. Therefore, this study aimed to investigate the effects of pharmacological doses of copper on the microbial communities in the hindgut and the antimicrobial resistance profiles of E. coli in weaned piglets. Twenty-four healthy weaned piglets aged 21 ± 1 days and with an average weight of 7.27 ± 0.46 kg were randomly divided into four groups. The control group was fed a basal diet, while the treatment groups were fed a basal diet supplemented with 20, 100, or 200 mg copper/kg feed, in the form of CuSO4. Anal swabs were collected at 0, 21, and 42 days of the trial, and E. coli was isolated. Meanwhile, the contents of the ileum and cecum from the control and 200 mg copper/kg feed groups were collected at 21 and 42 days for microbial community analysis and E. coli isolation. All isolated E. coli strains were used for antimicrobial resistance profile analysis. A pharmacological dose of copper did not significantly change the diversity, but significantly affected the composition, of microbial communities in the ileum and cecum. Moreover, it affected the microbial metabolic functions of energy metabolism, protein metabolism, and amino acid biosynthesis. Specifically, copper treatment increased the richness of E. coli in the hindgut and the rates of E. coli resistance to chloramphenicol and ciprofloxacin. Moreover, the rate of E. coli resistance to multiple drugs increased in the ileum of pigs fed a pharmacological dose of copper. Thus, a pharmacological dose of copper affected the composition of the microbial community, increased the antimicrobial resistance rates of intestinal E. coli, and was most likely harmful to the health of piglets at the early stage after weaning.

Low Dosage of Chitosan Supplementation Improves Intestinal Permeability and Impairs Barrier Function in Mice.

The purpose of this study was to explore relationships between low dose dietary supplementation with chitosan (COS) and body weight, feed intake, intestinal barrier function, and permeability in mice. Twenty mice were randomly assigned to receive an unadulterated control diet (control group) or a dietary supplementation with 30 mg/kg dose of chitosan (COS group) for two weeks. Whilst no significant differences were found between the conditions for body weight or food and water intake, mice in the COS group had an increased serum D-lactate content (P < 0.05) and a decreased jejunal diamine oxidase (DAO) activity (P < 0.05). Furthermore, mice in COS group displayed a reduced expression of occludin and ZO-1 (P < 0.05) and a reduced expression of occludin in the ileum (P < 0.05). The conclusion drawn from these findings showed that although 30 mg/kg COS-supplemented diet had no effect on body weight or feed intake in mice, this dosage may compromise intestinal barrier function and permeability. This research will contribute to the guidance on COS supplements.