scholarly journals Adaptation of the gut holobiont to malnutrition during mouse pregnancy depends on the type of nutritional adversity

2021 ◽  
Author(s):  
Kristin Connor ◽  
Enrrico Bloise ◽  
Todd Z DeSantis ◽  
Stephen J Lye
Keyword(s):  
Control Diet ◽  
Inflammatory Biomarkers ◽  
Mrna Levels ◽  
Cancer Resistance ◽  
Glycoprotein P ◽  
Microbiome Composition ◽  
Maternal Adaptation ◽  
Systems Physiology ◽  
And Function ◽  
Transporter Expression

Malnutrition can influence maternal physiology and programme offspring development. Yet, in pregnancy, little is known about how dietary challenges that influence maternal phenotype affect gut structure and function. Emerging evidence suggests that interactions between the environment, multidrug resistance (MDR) transporters and microbes may influence maternal adaptation to pregnancy and regulate fetoplacental development. We hypothesised that the pregnancy gut holobiont (host and microbes) adapts differently to suboptimal maternal diets, evidenced by changes in the gut microenvironment, morphology, and expression of key protective MDR transporters during pregnancy. Mice were fed a control diet (CON) during pregnancy, or undernourished (UN) by 30% of control intake from gestational day (GD)5.5-18.5, or fed 60% high fat diet (HF) for eight weeks before and during pregnancy. At GD18.5, maternal small intestinal (SI) architecture (H&E), proliferation (Ki67), P-glycoprotein (P-gp - encoded by Abcb1a/b) and breast cancer resistance protein (BCRP/Abcg2) MDR transporter expression and levels of pro-inflammatory biomarkers were assessed. Circulating inflammatory biomarkers and maternal caecal microbiome composition (G3 PhyloChipTM) were measured. MDR transporter expression was also assessed in fetal gut. HF diet increased maternal SI crypt depth and proinflammatory load, and decreased SI expression of Abcb1a mRNA, whilst UN increased SI villi proliferation and Abcb1a, but decreased Abcg2, mRNA expression. There were significant associations between Abcb1a and Abcg2 mRNA levels with relative abundance of specific microbial taxa. Using a systems physiology approach we report that common nutritional adversities provoke adaptations in the pregnancy holobiont in mice, and reveal new mechanisms that could influence reproductive outcomes and fetal development.

Hexose transporter expression in rat small intestine: effect of diet on diurnal variations

1996 ◽  
Vol 271 (1) ◽  
pp. G211-G216 ◽  
Author(s):  
C. P. Corpe ◽  
C. F. Burant
Keyword(s):  
Daily Variation ◽  
Control Diet ◽  
Diurnal Variations ◽  
Mrna Levels ◽  
Hexose Transporter ◽  
Diurnal Pattern ◽  
Protein Levels ◽  
Feeding Study ◽  
Hexose Transporters ◽  
Transporter Expression

In rodents, a number of intestinal digestive and absorptive processes demonstrate a diurnal pattern of activity. To investigate if the jejunal hexose transporters are regulated in such a diurnal fashion, the levels for the glucose and fructose transporter mRNA and proteins were determined at 6-h intervals over a 24-h control fed period. SGLT-1, GLUT-2, and GLUT-5 mRNA levels increased between two- and eightfold before the onset of peak feeding. GLUT-5 protein levels also varied in a diurnal fashion but were out of phase with the observed changes in GLUT-5 mRNA levels. In contrast, GLUT-2 protein levels remained relatively constant during the control fed 24-h period. The effect of dietary manipulations on the observed diurnal variation was also investigated. After only 3 h of feeding a 60% fructose-enriched diet, the levels of GLUT-5 mRNA and protein were significantly elevated. GLUT-5 mRNA and protein levels remained elevated relative to the level of control diet-fed animals over the ensuing 24 h and during the 7th day of fructose feeding. Exposure to elevated levels of fructose had no significant effect on the diurnal pattern of GLUT-2 and SGLT-1 mRNA. In contrast, GLUT-2 protein was rapidly downregulated during the length of the fructose feeding study. In conclusion, the data demonstrate a normal daily variation in the level of hexose transporter expression that can be rapidly modulated by diet.

scholarly journals Chorioamnionitis Induces a Specific Signature of Placental ABC Transporters Associated with an Increase of miR-331-5p in the Human Preterm Placenta

2018 ◽  
Vol 45 (2) ◽  
pp. 591-604 ◽  
Author(s):  
Guinever Eustaquio do Imperio ◽  
Enrrico Bloise ◽  
Mohsen Javam ◽  
Phetcharawan Lye ◽  
Andrea Constantinof ◽  
...  
Keyword(s):  
Abc Transporter ◽  
Abc Transporters ◽  
Staining Intensity ◽  
Distinct Pattern ◽  
Mrna Levels ◽  
Cancer Resistance ◽  
Glycoprotein P ◽  
Immunological Responses

Background/Aims: The ATP-binding cassette (ABC) transporters mediate drug biodisposition and immunological responses in the placental barrier. In vitro infective challenges alter expression of specific placental ABC transporters. We hypothesized that chorioamnionitis induces a distinct pattern of ABC transporter expression. Methods: Gene expression of 50 ABC transporters was assessed using TaqMan® Human ABC Transporter Array, in preterm human placentas without (PTD; n=6) or with histological chorioamnionitis (PTDC; n=6). Validation was performed using qPCR, immunohistochemistry and Western blot. MicroRNAs known to regulate P-glycoprotein (P-gp) were examined by qPCR. Results: Up-regulation of ABCB9, ABCC2 and ABCF2 mRNA was detected in chorioamnionitis (p<0.05), whereas placental ABCB1 (P-gp; p=0.051) and ABCG2 (breast cancer resistance protein-BCRP) mRNA levels (p=0.055) approached near significant up-regulation. In most cases, the magnitude of the effect significantly correlated to the severity of inflammation. Upon validation, increased placental ABCB1 and ABCG2 mRNA levels (p<0.05) were observed. At the level of immunohistochemistry, while BCRP was increased (p<0.05), P-gp staining intensity was significantly decreased (p<0.05) in PTDC. miR-331-5p, involved in P-gp suppression, was upregulated in PTDC (p<0.01) and correlated to the grade of chorioamnionitis (p<0.01). Conclusions: Alterations in the expression of ABC transporters will likely lead to modified transport of clinically relevant compounds at the inflamed placenta. A better understanding of the potential role of these transporters in the events surrounding PTD may also enable new strategies to be developed for prevention and treatment of PTD.

scholarly journals Differential Effects of Chrysin on Nitrofurantoin Pharmacokinetics Mediated by Intestinal Breast Cancer Resistance Protein in Rats and Mice

2009 ◽  
Vol 12 (2) ◽  
pp. 150 ◽  
Author(s):  
Atsushi Kawase ◽  
Yukako Matsumoto ◽  
Motoshi Hadano ◽  
Yui Ishii ◽  
Masahiro Iwaki
Keyword(s):  
Breast Cancer ◽  
Small Intestine ◽  
Breast Cancer Resistance Protein ◽  
Plasma Concentrations ◽  
Mrna Levels ◽  
Cancer Resistance ◽  
Glycoprotein P ◽  
Metabolizing Enzymes ◽  
Resistance Protein ◽  
Rats And Mice

PURPOSE: The activities of breast cancer resistance protein (Bcrp/ABCG2) as well as P-glycoprotein (P-gp) and drug-metabolizing enzymes can be inhibited by several flavonoids or drugs in rats. However, the species, gender and regional differences of effects of flavonoids on Bcrp/ABCG2 in rats and mice remain unclear, although Bcrp, like P-gp, is also important in controlling drug absorption and disposition. METHODS: We used chrysin as a model flavonoid because it possesses anti-inflammatory and antioxidative properties and is used as a dietary supplement. We examined the pharmacokinetics of nitrofurantoin, a specific Bcrp substrate, in rats and mice treated with chrysin. Bcrp mRNA levels were measured in liver, kidney, duodenum, jejunum and ileum in rats and mice. RESULTS: Plasma concentrations of nitrofurantoin were increased in rats, but not mice, treated with oral chrysin, compared with untreated controls. Intraperitoneal injection of chrysin into rats or mice had little effect on the elimination of nitrofurantoin, compared with untreated animals. CONCLUSIONS: These results suggest that chrysin-nitrofurantoin interactions occur in the small intestine in rats, but not in mice, possibly due to the higher levels of Bcrp expression in the small intestine in rats, compared with those in mice.

scholarly journals Consumption of a Western-Style Diet Modulates the Response of the Murine Gut Microbiome to Ciprofloxacin

mSystems ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Damien J. Cabral ◽  
Jenna I. Wurster ◽  
Benjamin J. Korry ◽  
Swathi Penumutchu ◽  
Peter Belenky
Keyword(s):  
Gut Microbiome ◽  
Transcriptional Activity ◽  
Control Diet ◽  
Structure And Function ◽  
Western Diet ◽  
Content Type ◽  
Microbiome Composition ◽  
Host Diet ◽  
And Function ◽  
The Impact

ABSTRACT Dietary composition and antibiotic use have major impacts on the structure and function of the gut microbiome, often resulting in dysbiosis. Despite this, little research has been done to explore the role of host diet as a determinant of antibiotic-induced microbiome disruption. Here, we utilize a multi-omic approach to characterize the impact of Western-style diet consumption on ciprofloxacin-induced changes to gut microbiome structure and transcriptional activity. We found that Western diet consumption dramatically increased Bacteroides abundances and shifted the community toward the metabolism of simple sugars and mucus glycoproteins. Mice consuming a Western-style diet experienced a greater expansion of Firmicutes following ciprofloxacin treatment than those eating a control diet. Transcriptionally, we found that ciprofloxacin reduced the abundance of tricarboxylic acid (TCA) cycle transcripts on both diets, suggesting that carbon metabolism plays a key role in the response of the gut microbiome to this antibiotic. Despite this, we observed extensive diet-dependent differences in the impact of ciprofloxacin on microbiota function. In particular, at the whole-community level we detected an increase in starch degradation, glycolysis, and pyruvate fermentation following antibiotic treatment in mice on the Western diet, which we did not observe in mice on the control diet. Similarly, we observed diet-specific changes in the transcriptional activity of two important commensal bacteria, Akkermansia muciniphila and Bacteroides thetaiotaomicron, involving diverse cellular processes such as nutrient acquisition, stress responses, and capsular polysaccharide (CPS) biosynthesis. These findings demonstrate that host diet plays a role in determining the impacts of ciprofloxacin on microbiome composition and microbiome function. IMPORTANCE Due to the growing incidence of disorders related to antibiotic-induced dysbiosis, it is essential to determine how our “Western”-style diet impacts the response of the microbiome to antibiotics. While diet and antibiotics have profound impacts on gut microbiome composition, little work has been done to examine their combined effects. Previous work has shown that nutrient availability, influenced by diet, plays an important role in determining the extent of antibiotic-induced disruption to the gut microbiome. Thus, we hypothesize that the Western diet will shift microbiota metabolism toward simple sugar and mucus degradation and away from polysaccharide utilization. Because of bacterial metabolism’s critical role in antibiotic susceptibility, this change in baseline metabolism will impact how the structure and function of the microbiome are impacted by ciprofloxacin exposure. Understanding how diet modulates antibiotic-induced microbiome disruption will allow for the development of dietary interventions that can alleviate many of the microbiome-dependent complications of antibiotic treatment.

scholarly journals Consumption of a Western-style diet modulates the response of the murine gut microbiome to ciprofloxacin

2019 ◽  
Author(s):  
Damien J. Cabral ◽  
Jenna I. Wurster ◽  
Benjamin J. Korry ◽  
Swathi Penumutchu ◽  
Peter Belenky
Keyword(s):  
Antibiotic Treatment ◽  
Stress Responses ◽  
Gut Microbiome ◽  
Transcriptional Activity ◽  
Control Diet ◽  
Transcriptional Level ◽  
Microbiome Composition ◽  
Host Diet ◽  
And Function ◽  
The Impact

AbstractDietary composition and antibiotic use are known to have major impacts on the structure and function of the gut microbiome, often resulting in dysbiosis. Despite this, little research has been done to explore the role of host diet as a determinant of antibiotic-induced microbiome disruption.Here, we utilize a multi-omic approach to characterize the impact of Western-style diet consumption on ciprofloxacin-induced changes to gut microbiome community structure and transcriptional activity. We found that mice consuming a Western-style diet experienced a greater expansion of Firmicutes following ciprofloxacin treatment than those eating a control diet. At the transcriptional level, we found that ciprofloxacin induced a reduction in the abundance of TCA cycle transcripts on both diets, suggesting that carbon metabolism plays a key role in the response of the gut microbiome to this antibiotic. Despite this shared response, we observed extensive differences in the response of the microbiota to ciprofloxacin on each diet. In particular, at the whole-community level we detected an increase in starch degradation, glycolysis, and pyruvate fermentation following antibiotic treatment in mice on the Western diet, which we did not observe in mice on the control diet. Similarly, we observed diet-specific changes in the transcriptional activity of two important commensal bacteria, Akkermansia muciniphila and Bacteroides thetaiotaomicron, involving diverse cellular processes such as nutrient acquisition, stress responses, and capsular polysaccharide (CPS) biosynthesis. These findings demonstrate that host diet plays a key role in determining the extent of disruption of microbiome composition and function induced by antibiotic treatment.ImportanceWhile both diet and antibiotics are individually known to have profound impacts on gut microbiome composition, little work has been done to examine the effect of these two factors combined. A number of negative health outcomes, including diabetes and obesity, are associated with diets high in simple sugars in fats but low in host-indigestible fiber, and some of these outcomes may be mediated by the gut microbiome. Likewise, treatment with broad-spectrum antibiotics and the resulting dysbiosis is associated with many of the same detrimental side effects. Previous work has shown that nutrient availability, as influenced by host diet, plays an important role in determining the extent of antibiotic-induced disruption to the gut microbiome. Due to the growing incidence of disorders related to antibiotic-induced dysbiosis, it is essential to determine how the prevalence of high fat and sugar “Western”-style diets impacts the response of the microbiome to antibiotics.

scholarly journals 52 Alterations of fecal microbiome characteristics by dietary soy isoflavone ingestion in growing pigs infected with porcine reproductive and respiratory syndrome virus

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 30-31
Author(s):  
Brooke N Smith ◽  
Stephen A Fleming ◽  
Mei Wang ◽  
Ryan N Dilger
Keyword(s):  
Control Diet ◽  
Growing Pigs ◽  
Respiratory Syndrome Virus ◽  
Post Inoculation ◽  
Long Term Effects ◽  
Unifrac Distance ◽  
Fecal Microbiome ◽  
Microbiome Composition ◽  
Time Points ◽  
Experimental Treatments

Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically-important disease and ingestion of soy isoflavones (ISF) may benefit PRRSV-infected pigs due to demonstrated anti-inflammatory and anti-viral properties. The objective of this study was to quantify long-term effects of ISF consumption on fecal microbiome characteristics under disease challenge. In total, 96 weaned barrows were group-housed in a BSL-2 containment facility and allotted to 1 of 3 experimental treatments that were maintained throughout the wean-to-finish study: non-infected pigs receiving an ISF-devoid control diet (NC, n=24), and infected pigs receiving either the control diet (PC, n=36) or that supplemented with total ISF in excess of 1,600 mg/kg (ISF, n=36) (Table 1). Following a 7-day adaptation, pigs were inoculated intranasally with either a sham-control (PBS) or live PRRSV (1×105 TCID50/mL, strain NADC20). Fecal samples were collected from 48 individual pigs at pre-infection (-2 days post-inoculation, DPI), peak-infection (10 DPI), and post-infection (144 DPI) time-points and extracted DNA was used for 16S bacterial rRNA sequencing. Differences in bacterial communities among diet groups were evaluated using UniFrac distance matrices (weighted and unweighted) in QIIME. All other data were analyzed by one-way ANOVA performed on transformed data using R. Across all time-points, only minimal differences were observed due to ISF alone. At 10 DPI, PRRSV infection reduced Prevotella 9 genera abundance from approximately 20% to less than 10%, but the specific function of this variety in pigs is unclear. The most notable finding was decreased relative abundance of Actinobacteria at 144 DPI between non-infected and infected treatments (P &lt; 0.05), which is consistent with various dysbioses observed in other disease models. Our findings indicate that differences present were mainly due to PRRSV infection and not strongly influenced by ISF ingestion, which implies previously observed performance benefits conferred by dietary ISF are not likely due to changes in microbiome composition.

scholarly journals Spinal Cord Injury Increases Pro-inflammatory Cytokine Expression in Kidney at Acute and Sub-chronic Stages

Inflammation ◽  
2021 ◽  
Author(s):  
Shangrila Parvin ◽  
Clintoria R. Williams ◽  
Simone A. Jarrett ◽  
Sandra M. Garraway
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Inflammatory Cytokine ◽  
Cardiovascular Health ◽  
Mrna Levels ◽  
Post Injury ◽  
Cord Injury ◽  
And Function ◽  
The Impact

Abstract— Accumulating evidence supports that spinal cord injury (SCI) produces robust inflammatory plasticity. We previously showed that the pro-inflammatory cytokine tumor necrosis factor (TNF)α is increased in the spinal cord after SCI. SCI also induces a systemic inflammatory response that can impact peripheral organ functions. The kidney plays an important role in maintaining cardiovascular health. However, SCI-induced inflammatory response in the kidney and the subsequent effect on renal function have not been well characterized. This study investigated the impact of high and low thoracic (T) SCI on C-fos, TNFα, interleukin (IL)-1β, and IL-6 expression in the kidney at acute and sub-chronic timepoints. Adult C57BL/6 mice received a moderate contusion SCI or sham procedures at T4 or T10. Uninjured mice served as naïve controls. mRNA levels of the proinflammatory cytokines IL-1β, IL-6, TNFα, and C-fos, and TNFα and C-fos protein expression were assessed in the kidney and spinal cord 1 day and 14 days post-injury. The mRNA levels of all targets were robustly increased in the kidney and spinal cord, 1 day after both injuries. Whereas IL-6 and TNFα remained elevated in the spinal cord at 14 days after SCI, C-fos, IL-6, and TNFα levels were sustained in the kidney only after T10 SCI. TNFα protein was significantly upregulated in the kidney 1 day after both T4 and T10 SCI. Overall, these results clearly demonstrate that SCI induces robust systemic inflammation that extends to the kidney. Hence, the presence of renal inflammation can substantially impact renal pathophysiology and function after SCI.

scholarly journals Restoration of Noradrenergic Function in Parkinson’s Disease Model Mice

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110097
Author(s):  
Kui Cui ◽  
Fan Yang ◽  
Turan Tufan ◽  
Muhammad U. Raza ◽  
Yanqiang Zhan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factors ◽  
Disease Model ◽  
Neuronal Loss ◽  
Mrna Levels ◽  
Gene Therapies ◽  
Protein Levels ◽  
Dopaminergic Systems ◽  
And Function

Dysfunction of the central noradrenergic and dopaminergic systems is the primary neurobiological characteristic of Parkinson’s disease (PD). Importantly, neuronal loss in the locus coeruleus (LC) that occurs in early stages of PD may accelerate progressive loss of dopaminergic neurons. Therefore, restoring the activity and function of the deficient noradrenergic system may be an important therapeutic strategy for early PD. In the present study, the lentiviral constructions of transcription factors Phox2a/2b, Hand2 and Gata3, either alone or in combination, were microinjected into the LC region of the PD model VMAT2 Lo mice at 12 and 18 month age. Biochemical analysis showed that microinjection of lentiviral expression cassettes into the LC significantly increased mRNA levels of Phox2a, and Phox2b, which were accompanied by parallel increases of mRNA and proteins of dopamine β-hydroxylase (DBH) and tyrosine hydroxylase (TH) in the LC. Furthermore, there was considerable enhancement of DBH protein levels in the frontal cortex and hippocampus, as well as enhanced TH protein levels in the striatum and substantia nigra. Moreover, these manipulations profoundly increased norepinephrine and dopamine concentrations in the striatum, which was followed by a remarkable improvement of the spatial memory and locomotor behavior. These results reveal that over-expression of these transcription factors in the LC improves noradrenergic and dopaminergic activities and functions in this rodent model of PD. It provides the necessary groundwork for the development of gene therapies of PD, and expands our understanding of the link between the LC-norepinephrine and dopamine systems during the progression of PD.

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