A Ketogenic Diet Is Protective Against Atherosclerosis in Apolipoprotein E Knockout Mice

Abstract Objectives A ketogenic diet (KD) positively impacts cardiovascular disease (CVD) risk factors yet its effect on atherosclerosis, the main cause of CVD, is elusive. We hypothesize that, when compared to a high-fat diet (HF), KD protects from atherosclerosis. Methods Seven-week-old male Apoe−/− mice, a model for human atherosclerosis, were fed ad libitum (%kcal) KD (81-fat, 1-carbohydrate, 18-protein; n = 4) or HF (40-fat, 42-carbohydrate, 18-protein; n = 5). After 4, 8 and 12 weeks, plasma was collected and used to (1) quantify beta-hydroxybutyrate levels (OH-But) by a colorimetric assay; or (2) assess systemic inflammation, a key feature associated with atherosclerosis, using a panel of inflammatory cytokines; or (3) explore diet-driven changes in levels of atherosclerosis-relevant metabolites using a targeted metabolomic approach by triple quadrupole mass spectrometry. At the endpoint, mice were euthanized and their perfusion-fixed aortas were subjected to 3-D analysis by magnetic resonance imaging to quantify the extent of atherosclerosis. Data were reconstructed using Matlab and segmented to obtain atherosclerotic plaque volumes using Avizo 9.0. Results The inflammatory cytokines were significantly (P < 0.05, Student's t-test) elevated in HF-mice compared to KD-mice after 12 weeks; MIP-1α, (25 ± 13 vs 13 ± 4 pg/mol), MCP-1 (165 ± 67 vs 69 ± 23 pg/mol), TNF-α(51 ± 17 vs 35 ± 5 pg/mol), and IL-1β (2 ± 2 vs 0.6 ± 0.1 pg/mol). OH-But levels were always significantly higher in KD-mice than in HF-mice, thus confirming the presence of ketosis in KD-mice. Significant changes in the plasma metabolome of KD-mice, when compared to HF-mice, were present for dimethylated arginines, gut-derived metabolites, certain bile acids, some acylcarnitines and ceramides, certain sphingolipids and cholesterol esters, and constituents of the major intracellular antioxidant glutathione. Lastly, aortic plaque burden was significantly decreased in KD mice (2.77 ± 1.02%) than in HF mice (13.94 ± 3.72%). Conclusions KD was associated with decreased inflammation, changes in several metabolic intermediates and an atheroprotective effect based on MRI analysis. Funding Sources Huck Institutes of the Life Sciences; Graduate Program in Nutritional Sciences.

Download Full-text

Diet-Induced Mild Hyperhomocysteinemia in Mice Fed a Ketogenic Diet Does Not Alter the Development of Atherosclerosis nor Specific Epigenetic Content

Current Developments in Nutrition ◽

10.1093/cdn/nzab050_020 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 953-953

Author(s):

Courtney Whalen ◽

Sean Gullette ◽

Floyd Mattie ◽

Thomas Neuberger ◽

A Catharin Ross ◽

...

Keyword(s):

Colorimetric Assay ◽

Plaque Burden ◽

Vascular Toxicity ◽

Methyl Donors ◽

Atherosclerosis Progression ◽

Methylation Index ◽

Funding Sources ◽

Ketogenic Diets ◽

Mild Hyperhomocysteinemia ◽

Beta Hydroxybutyrate

Abstract Objectives Elevated plasma homocysteine (Hcy), or hyperhomocysteinemia (HHcy), is a risk factor for atherosclerosis by mechanisms still elusive. A possibility includes the alteration of specific epigenetic tags at lysine 27 of histone H3 (H3K27) due to hypomethylating stress. Similarly, ketogenic diets (KD), or very-low carbohydrate diets, which stimulate ketosis, and may also affect the epigenetic content on the H3K27 residue. Studies connecting the effects of dietary ketosis, mild HHcy, and specific epigenetic dysregulation are lacking. We hypothesize that diet-induced HHcy and ketosis will induce H3K27 hypomethylation combined with increased acetylation to produce a pro-atherogenic phenotype. Methods Seven-week-old male apoe−/− (apolipoprotein E-deficient) mice, a model for human atherosclerosis, were fed ad libitum a KD (in %kcal: fat, 81; carbohydrate, 1; protein, 18; n = 4–6) or HHcy-KD (same macronutrients, with added methionine and reduced methyl donors; n = 4). After 4, 8 and 12 wk of diet treatment, plasma was collected to quantify ketosis via beta-hydroxybutyrate levels (OH-But) by a colorimetric assay, and measure Hcy by HPLC. At the endpoint, mice were euthanized and aortas were collected for quantification of the vascular methylation index, S-adenosylmethionine to S-adenosylHcy ratio by LC-MS-MS; 3-D analysis of the atherosclerotic plaque burden by magnetic resonance imaging; and quantification of the epigenetic tags H3K27me3 and H3K27ac using immunohistochemistry. Results A sustained ketosis was detected through elevated OH-But levels in both KD and HHcy-KD mice. HHcy was mildly but significantly (P < 0.05) elevated in HHcy-KD-mice compared to KD-mice after 4 wk (19.5 ± 2.3 vs 4.5 ± 0.6 µM) and 12 wk (17.2 ± 2.1 vs 4.4 ± 0.9 µM). Nevertheless, no significant differences were observed in aortic methylation index, plaque accumulation, or content of the H3K27me3 or H3K27ac epigenetic tags between the two groups of mice. Conclusions While mild HHcy was achieved in HHcy-KD mice, this phenotype failed to induce vascular hypomethylation, atherosclerosis progression or specific epigenetic dysregulation, suggesting that a more severe Hcy accumulation may be necessary to cause vascular toxicity and specific epigenetic dysregulation. Funding Sources Huck Institutes of the Life Sciences

Download Full-text

Effects of Two Months of Very Low Carbohydrate Ketogenic Diet on Body Composition, Muscle Strength, Muscle Area, and Blood Parameters in Competitive Natural Body Builders

Nutrients ◽

10.3390/nu13020374 ◽

2021 ◽

Vol 13 (2) ◽

pp. 374

Author(s):

Antonio Paoli ◽

Lorenzo Cenci ◽

PierLuigi Pompei ◽

Nese Sahin ◽

Antonino Bianco ◽

...

Keyword(s):

Body Composition ◽

Muscle Strength ◽

Ketogenic Diet ◽

Inflammatory Cytokines ◽

Blood Parameters ◽

Maximal Strength ◽

Muscle Area ◽

Low Carbohydrate ◽

Before And After ◽

Adequate Quantity

Background: Ketogenic diet (KD) is a nutritional approach that restricts daily carbohydrates, replacing most of the reduced energy with fat, while maintaining an adequate quantity of protein. Despite the widespread use of KD in weight loss in athletes, there are still many concerns about its use in sports requiring muscle mass accrual. Thus, the present study sought to investigate the influence of a KD in competitive natural body builders. Methods: Nineteen volunteers (27.4 ± 10.5 years) were randomly assigned to ketogenic diet (KD) or to a western diet (WD). Body composition, muscle strength and basal metabolic rate were measured before and after two months of intervention. Standard blood biochemistry, testosterone, IGF-1, brain-derived neurotrophic factor (BDNF) and inflammatory cytokines (IL6, IL1β, TNFα) were also measured. Results: Body fat significantly decreased in KD (p = 0.030); whilst lean mass increased significantly only in WD (p < 0.001). Maximal strength increased similarly in both groups. KD showed a significant decrease of blood triglycerides (p < 0.001), glucose (p = 0.001), insulin (p < 0.001) and inflammatory cytokines compared to WD whilst BDNF increased in both groups with significant greater changes in KD (p < 0.001). Conclusions: KD may be used during body building preparation for health and leaning purposes but with the caution that hypertrophic muscle response could be blunted.

Download Full-text

Aspartame Intake Relates to Coronary Plaque Burden and Inflammatory Indices in Human Immunodeficiency Virus

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx083 ◽

2017 ◽

Vol 4 (2) ◽

Cited By ~ 3

Author(s):

Leangelo N. Hall ◽

Laura R. Sanchez ◽

Jane Hubbard ◽

Hang Lee ◽

Sara E. Looby ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Cardiac Computed Tomography ◽

Coronary Plaque ◽

Plaque Burden ◽

Artificial Sweetener ◽

Food Record ◽

Cvd Risk ◽

Cardiac Computed Tomography Angiography ◽

Markers Of Inflammation ◽

Immunodeficiency Virus

Abstract Background Dietary sweeteners may contribute to metabolic dysregulation and cardiovascular disease (CVD), but this has not been assessed in human immunodeficiency virus (HIV). Methods One hundred twenty-four HIV-infected and 56 non-HIV-infected participants, without history of known coronary artery disease were included. Dietary intake was assessed using a 4-day food record. Coronary plaque was determined using cardiac computed tomography angiography. Results Human immunodeficiency virus-infected participants had significantly greater intake of dietary sweeteners, including total sugar (P = .03) and added sugar (P = .009); intake of aspartame (artificial sweetener) was greater among aspartame consumers with HIV versus non-HIV consumers (P = .03). Among HIV-infected participants, aspartame intake was significantly associated with coronary plaque (P = .002) and noncalcified plaque (P = .007) segments, as well as markers of inflammation/immune activation (monocyte chemoattractant protein 1 and lipoprotein-associated phospholipase A2), which may contribute to increased atherogenesis. In multivariable regression modeling, aspartame remained an independent predictor of plaque in HIV. In contrast, among non-HIV-infected participants, no sweetener type was shown to relate to plaque characteristics. Conclusions We demonstrate increased intake of dietary sweeteners and a potential novel association between aspartame intake, plaque burden, and inflammation in HIV. Our data suggest that aspartame may contribute to CVD risk in HIV. Further studies should address potential mechanisms by which aspartame may contribute to increased plaque burden and cardiovascular benefits of dietary strategies targeting aspartame intake in HIV.

Download Full-text

Coronary Inflammation Assessed by Perivascular Fat Attenuation Index in Patients with Psoriasis: A Propensity Score-Matched Study

Dermatology ◽

10.1159/000518771 ◽

2021 ◽

pp. 1-9

Author(s):

Wenrui Bao ◽

Min Yang ◽

Zhihan Xu ◽

Fuhua Yan ◽

Qi Yang ◽

...

Keyword(s):

Computed Tomography ◽

Coronary Plaque ◽

Plaque Burden ◽

Control Group ◽

Low Grade ◽

Cvd Risk ◽

Control Subjects ◽

Atherosclerotic Burden ◽

Attenuation Index ◽

Perivascular Fat

Objectives: This study aimed to evaluate coronary inflammation by measuring the perivascular fat attenuation index (FAI) and quantify the atherosclerosis burden in patients with psoriasis and control individuals without psoriasis based on coronary computed tomography angiography (CCTA) images. Methods: A total of 98 consecutive patients with psoriasis (76 male [77.6%], aged 56.5 years, range 45.5–65.0) were recruited, and 196 patients (157 male [80.1%]; aged 54.6 ± 14.1 years) without established cardiovascular disease (CVD) who underwent CCTA within the same period were enrolled in the control group. Coronary plaque burden was quantified using the computed tomography-adapted Leaman score (CT-LeSc), and the FAI surrounding the proximal of three main epicardial vessels was measured to represent coronary inflammation. Results: Patients with psoriasis and the control subjects were well matched in CVD risk factors (all p > 0.05). Psoriasis patients had a greater overall CT-LeSc (5.86 vs. 4.69, p = 0.030) and lower perivascular FAI (−80.19 ± 7.48 vs. −78.14 ± 7.81 HU, p < 0.001). A similar result was found upon comparing psoriasis patients without biological or statin therapy with non-psoriasis individuals without statin treatments. Furthermore, the psoriasis group had a higher prevalence of non-calcified plaques (30.3% in the psoriasis group vs. 20.1% in the control subjects, p = 0.001). No difference in perivascular FAI on either calcified and mixed plaques or non-calcified plaques between the two groups was found. Conclusion: Patients with psoriasis have a higher atherosclerotic burden as quantified by CT-LeSc and less coronary inflammation as detected by perivascular FAI around the most proximal of the three major epicardial vessels. The usefulness of perivascular FAI for evaluating coronary inflammation in patients with chronic low-grade inflammatory disease such as psoriasis should be verified.

Download Full-text

Remnant cholesterol is an independent determinant of the presence and extent of subclinical carotid atherosclerosis in statin-naive individuals

European Heart Journal ◽

10.1093/eurheartj/ehab724.2561 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

D Delialis ◽

E Aivalioti ◽

G Mavraganis ◽

A M Dimopoulou ◽

A Sianis ◽

...

Keyword(s):

Wall Thickness ◽

Carotid Atherosclerosis ◽

Intima Media Thickness ◽

Cholesterol Content ◽

Plaque Burden ◽

Cardiac Events ◽

Cvd Risk ◽

Therapeutic Algorithms ◽

Remnant Cholesterol

Abstract Background Despite continuous improvements of diagnostic and therapeutic algorithms for cardiovascular disease (CVD), mortality from CVD remains high suggesting unaddressed residual risk. Remnant cholesterol (RC) consists the cholesterol content of triglyceride-rich lipoproteins, which along with LDL cholesterol infiltrate the arterial wall, accumulate and cause atherosclerosis. Increased remnant cholesterol (RC) levels have been previously associated with future adverse cardiac events despite hypolipidemic therapy. However, a mechanistic association of RC levels with human atherosclerosis in vivo has not been proven in a clinical setting. Purpose To evaluate the association of RC levels with the presence and extend of subclinical carotid atherosclerosis. Methods In this retrospective cohort study, 438 subjects from the Athens Vascular Registry without clinically overt CVD or treatment with statin were recruited. Atherosclerotic burden was assessed by B-mode carotid ultrasonography using: 1. Maximal carotid wall thickness [maxWT, the highest intima-media thickness (IMT) or highest atherosclerotic plaque thickness (PLQ) if present derived from all carotid sites], 2. Total thickness (sumWT, sum of maximal wall thickness), 3) high plaque burden (PLQ ≥2) and 4) average carotid IMT (avgIMT). RC was calculated using the formula RC=total cholesterol-LDL-C-HDL-C. Results Mean (SD) age was 54.8±12.4 years old with 41% being males. Subjects with RC>median (=18mg/dl) had higher sumWT (6.12±0.7 vs 5.57±1.7, p=0.002), maxWT (1.61±0.7 vs 1.43±0.7, p=0.008) and avgIMT (0.88±0.16 vs 0.83±0.16, p=0.003) vs RC<median.>median was associated with higher odds for increased sumWT (highest tertile, OR: 2.15 95% CI 1.26–3.66, p=0.006) and maxWT (OR: 2.15 95% CI: 1.38–3.33, p=0.001), and a higher plaque burden (≥2 plaques, OR: 2.1 95% CI 1.93–3.1, p<0.001) after adjustment for age, gender and systolic blood pressure, glomerular filtration rate, smoking, diabetes mellitus, body mass index and LDL-C Conclusion In a statin-naive population without clinically overt CVD, increased RC levels were associated with the presence and extend of subclinical carotid atherosclerosis. These findings provide novel mechanistic insight into mechanisms associated with increased CVD risk in individuals with high RC levels. FUNDunding Acknowledgement Type of funding sources: None.

Download Full-text

How and Why Diets Change Post Migration for Chinese Immigrants

Current Developments in Nutrition ◽

10.1093/cdn/nzab035_058 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 150-150

Author(s):

Sarah Lee ◽

Tammie S Choi ◽

Nicole Kellow ◽

Catherine Huggins

Keyword(s):

Nutrition Education ◽

Healthy Eating ◽

Dietary Habits ◽

Disease Risk ◽

Chinese Immigrants ◽

Structured Interview ◽

Dietary Change ◽

Cvd Risk ◽

Funding Sources ◽

Qualitative Interview Study

Abstract Objectives Cardiovascular disease (CVD) risk is disproportionally greater in Chinese immigrants in Australia compared with in China. Dietary acculturation is implicated as a CVD risk factor. This study aimed to explored Chinese immigrants’ perspectives on how and why their diets change post migration. Methods An exploratory qualitative interview study was undertaken with adult Chinese migrants who had been living in Australia for less than 10 years. Semi-structured interview questions were designed to draw out participants’ experience, emotions and thoughts of dietary change. Interviews were conducted via Zoom in participants’ preferred language (Mandarin or English). Interviews were transcribed verbatim and translated into English for analysis. A constructivist approach was adopted to thematically analyse the interviews. Results A total of 11 participants were interviewed (n = 3 males and n = 8 females) and ranged in age from 22–68 years old with length of residence in Australia ranging from 1–8 years. Key themes pertaining to how and why dietary changes that occur post migration are: that breakfast is the first meal to change from Chinese to Western style, convenience is one of the primary drivers of change in dietary habits, dinner is most frequently maintained in Chinese style, cultural identity is an important influence on dietary habits, and awareness of dietary change among Chinese immigrants is low as evidenced through statements such as “not much has changed” when asked about differences in their diet, but further probing identified that their post migration diets were quite different from their diets in China. Participants also reported a lack of general healthy eating knowledge and lack of nutrition education from China. Conclusions Though diets of Chinese immigrants to Australia change post migration, particularly in relation to breakfast, due to convenience, awareness of this change is low. Low awareness of dietary change along with lack of knowledge relating to healthy eating, could be a mechanism for adoption of unhealthy dietary patterns that may contribute to increased chronic disease risk for Chinese immigrants over time. Funding Sources No funding to declare.

Download Full-text

Abstract 501: Prevalence of Ascending Aorta Atherosclerosis as Detected by Echocardiography and Computed Tomography in Patients Referred for Atrial Fibrillation Ablation

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.501 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Efstratios Koutroumpakis ◽

Benjamin Schwartz ◽

John Espey ◽

Elizabeth Rau ◽

David Steckman ◽

...

Keyword(s):

Computed Tomography ◽

Transthoracic Echocardiography ◽

Left Atrial ◽

Ascending Aorta ◽

Plaque Burden ◽

Aortic Atherosclerosis ◽

Predictive Values ◽

Af Ablation ◽

Aortic Plaque ◽

Af Recurrence

Introduction: The prevalence and significance of thoracic aorta atherosclerosis in AF patients has not been clearly defined in the literature. There are scant reports supporting an association of atherosclerotic aortic plaque burden with embolic phenomena and recurrence of AF post ablation. Two modalities of aortic atherosclerosis detection include computed tomography (CT) and echocardiography. Hypothesis: The prevalence of ascending aorta atherosclerosis in AF patients is high and CT performs better than transthoracic echocardiography in its detection. Methods: We investigated prevalence of ascending aorta atherosclerosis by CT and transthoracic echocardiography in 76 consecutive patients referred for AF ablation (67.1% males, 62.9 +/- 9.8 years old, 6.6% active smokers, 75% paroxysmal AF, 13.1% with LV ejection fraction (EF) <50%, 61.8% with hyperlipidemia, 55.8% with hypertension, 10.5% with diabetes, 2.6% with chronic kidney disease, and 1 patient with peripheral artery disease). The pre-ablation echocardiograms and cardiac CT scans, originally performed for left atrial mapping and evaluation of left atrial appendage thrombus, were reviewed in a blinded fashion for the presence of aortic atherosclerosis. Results: Out of 76 AF ablation patients, 27 (35.5%) had evidence of ascending aorta atherosclerosis by CT and 43 (56.6%) by echocardiography. Using CT as the gold standard, echocardiography had a sensitivity of 70.4% and a specificity of 51% in identification of ascending aorta atherosclerosis. Positive and negative predictive values were 44.2% and 75.8%, respectively. A total of 16 patients (21.1%) had AF recurrence post ablation, out of which 6 (37.5%) had evidence of aortic atherosclerosis on CT (vs 21/49 [42.9%] in the non-recurrence group). Conclusions: Ascending aorta atherosclerosis is common in patients referred for AF ablation. Transthoracic echocardiography likely overestimates its prevalence. Aortic atherosclerosis as detected by CT was not significantly associated with AF recurrence post ablation. More studies investigating clinical implications and best treatment approach to subclinical aortic therosclerosis in patients with AF are needed.

Download Full-text

Effect of a Mediterranean Diet with Varying Quantities of Lean Beef on non-HDL and HDL Lipid Particles: A Randomized Controlled Feeding Cross-Over Trial (OR36-05-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz035.or36-05-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Jennifer Fleming ◽

Kristina Petersen ◽

Penny Kris-Etherton ◽

David Baer

Keyword(s):

Particle Number ◽

State University ◽

Cvd Risk ◽

Funding Sources ◽

Ldl Particles ◽

Lipid Panel ◽

Lean Beef ◽

Penn State ◽

Males And Females ◽

Clinical And Translational Research

Abstract Objectives To evaluate the effects of a Mediterranean (Med) style diet with varying quantities of lean beef on non-HDL and HDL lipid subspecies. We hypothesized that a Med diet with lean beef would confer cardiovascular benefits beyond a standard lipid panel and be superior to an average American diet (AAD). Methods We conducted a multicenter, 4-period controlled feeding, randomized crossover study at Penn State University and USDA-Beltsville to evaluate the effects of a Med diet (CHO 42%, PRO 17%, FAT 41%, SFA 8%, MUFA 26%, PUFA 8%) with different quantities of lean beef (0.5, 2.5 and 5.5 oz/day) compared to an average American diet (AAD; CHO 52%, PRO 15%, FAT 33%, SFA 12%, MUFA 13%, PUFA 8%) on CVD risk factors. Participants (n = 66) included generally healthy normal to overweight/obese males and females (BMI = 20–38 kg/m2) 30 to 67 years. Participants were randomized to each of the 4 diets for 4 weeks with an approximate 2-week break between treatments. Fasting blood samples were collected on two consecutive days at baseline (start of study), and at the end of each diet period. Results All three Med diets decreased LDL-C versus AAD (−10.5 ± 2.0, −9.0 ± 2.0, −6.8 ± 2.0 mg/dL, P < 0.0001 for the 0.5, 2.5 and 5.5 oz., respectively). All Med diets elicited similar reductions in total LDL particle number and large particle number (P < 0.01 for both) compared to baseline, however only the Med diets with 0.5 oz./day (−91.2 ± 23 nmol/L) and 2.5 oz./day (−85.3 ± 23 nmol/L) were significantly decreased versus AAD (P < 0.01). There were no treatment differences for IDL or small LDL particles. All diets reduced HDL-C and HDL particle number from baseline (P < 0.01). Conclusions A healthy Med style diet containing 2.5 oz./day of lean beef elicits similar improvements in lipid subspecies compared to a traditional Med style diet containing 0.5 oz./day. The Med style diet containing 5.5 oz./day of lean beef had similar effects on lipid subspecies to the AAD, therefore our findings suggest that £2.5 oz./day of lean beef can be included in a Med diet and not compromise the cardiovascular benefits of a Med diet. Funding Sources This study was funded by the Beef Checkoff. This study also was supported by the USDA, ARS and the Penn State Clinical and Translational Research Institute.

Download Full-text

Later Risk of Wheezing/Asthma and Allergy in Offspring of 2 Vitamin D (VitD) Pregnancy Cohorts: Post Hoc Analysis

Current Developments in Nutrition ◽

10.1093/cdn/nzaa054_168 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1096-1096

Author(s):

Carol Wagner ◽

Myla Ebeling ◽

Judy Shary ◽

John Baatz ◽

Danforth Newton ◽

...

Keyword(s):

Chi Square ◽

Childhood Health ◽

Post Hoc Analysis ◽

Funding Sources ◽

Long Term Effect ◽

Adverse Pregnancy ◽

Student’S T ◽

Post Hoc ◽

In Pregnancy

Abstract Objectives Maternal vitD deficiency as defined by circulating 25(OH)D concentration is linked with certain adverse pregnancy outcomes (e.g., preterm birth) and childhood outcomes (e.g., asthma), with the effect seemingly more pronounced if deficiency occurs earlier in pregnancy. OBJ: Assess the long-term effect of maternal and neonatal vitD status on later risk of childhood allergy, wheezing and/or asthma to 4 yrs. It was hypothesized that deficiency earlier in pregnancy would have a significant effect on risk that would continue during pregnancy. Methods In this follow-up post hoc analysis of women and their offspring enrolled in 1 of 2 pregnancy vitD supplementation trials (NICHD, n = 348 and Kellogg Foundation, n = 298), women were randomized to either 400, 2000 or 4000 IU vitD/day (NICHD) at 12–16 wks’ or 400 or 4400 IU/day at 10–14 wks’ (Kellogg). Baseline then monthly 25(OH)D concentration as the primary outcome in both studies and as the indicator of vitD status was measured by RIA until delivery. Neonatal vitD status was measured in cord blood. Follow-up data on the offspring were available through 4 yrs using an EMR with ICD-9 and 10 codes for eczema, wheezing and/or asthma. Student's t-test was used to analyze differences in mean 25(OH)D and eczema, wheezing, and asthma. Chi-square analyses were used to test for differences in incidence of 25(OH)D below 20, 30, and 40 and eczema, wheezing, and asthma. Results In NICHD Pregnancy, 326/348 (93.7%) offspring had EMR data available: 48 (14.7%) had eczema; 32 (9.8%) had wheezing; and 48 (14.7%) had asthma. In Kellogg Pregnancy, 205/298 (68.8%) had EMR data available; 36 (17.6%) had eczema; 14 (6.8%) had wheezing; and 10 (4.9%) had asthma. Maternal baseline 25(OH)D < 30 ng/mL was associated with eczema (P = 0.024) and asthma (P = 0.035) by age 4 yrs. Neonatal 25(OH)D was inversely associated with eczema (P = 0.01) and asthma by age 4 (P = 0.0012). When dichotomized, neonates with 25(OH)D < 20 ng/mL had a significantly higher risk of eczema (P = 0.02) and asthma (P = 0.004) and those below 40 ng/mL had a higher risk of eczema (P = 0.03). Conclusions In this combined cohort of pregnant women and their offspring, both maternal and neonatal vitD status were associated with later allergy, wheezing and asthma risk. Efforts to improve maternal vitD status may have later significant consequences on childhood health outcomes. Funding Sources NIH/NICHD/NCATS.

Download Full-text

The Role of Bacteriocin Producing Probiotic in Clostridium Difficile Colonization in Mice (P20-010-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz040.p20-010-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Gail Cresci ◽

Bryan Glueck

Keyword(s):

Clostridium Difficile ◽

Inflammatory Cytokines ◽

Bacterial Colonization ◽

Bacterial Overgrowth ◽

Treated Group ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Intestinal Integrity ◽

Funding Sources ◽

Intestinal Length

Abstract Objectives To test the efficacy of a spore-forming, bacteriocin-producing probiotic in mitigating intestinal Clostridium difficile colonization and injury in mice. Methods 10–12 week old female CF1 mice were treated with clindamycin for 3 days, followed by Clostridium difficile exposure (5log10 CFU). Stool samples were collected at baseline, following clindamycin treatment, and 1,3 and 5 days after C. difficile exposure. A separate group of mice were also supplemented with a bacteriocin/spore forming probiotic throughout the study period. Five days after C. difficile exposure mice were euthanized and intestine was dissected and the length was measured and then used to prepare RNA, protein lysate, histology, and cecum contents were analyzed for bacterial colonization. Results All mice exposed to clindamycin had overgrowth of enterococcus and gram negative bacteria and those exposed to C. difficile spores were positive for C. difficile colonization one day after exposure. Of interest, the probiotic supplemented mice resolved the overgrowth of enterococcus and gram negative bacteria as well as C. difficile colonization quicker than the saline treated group. The intestinal length was higher and cecum: body weight was lower in the probiotic supplemented mice compared to those treated with saline. These findings were associated with decreased mRNA expression of inflammatory cytokines and increased anti-inflammatory cytokines in the intestine. Conclusions A bacteriocin-producing probiotic accelerated resolution of bacterial overgrowth and C. difficile colonization and preserved mouse intestinal integrity during antibiotic-induced C. difficile colonization. These data suggest supplementation with a bacteriocin-producing probiotic may serve as a potential protective therapy during antibiotic exposure. Funding Sources Microbiome Labs.

Download Full-text