Probiotic and Muscadine Grape Extract Interventions Shift the Gut Microbiome and Improve Metabolic Parameters in Female C57BL/6 Mice.

Obesity and Western-like diet consumption leads to gut microbiome dysbiosis, which is associated with the development of cardio-metabolic diseases and poor health outcomes. The objective of this study was to reduce Western diet-mediated gut microbial dysbiosis, metabolic dysfunction, and systemic inflammation through the administration of a novel combined intervention strategy (oral probiotic bacteria supplements and muscadine grape extract (MGE)). To do so, adult female C57BL/6 mice were fed a low-fat control or Western-style diet and sub-grouped into diet alone, probiotic intervention, antibiotic treatments, MGE supplementation, a combination of MGE and probiotics, or MGE and antibiotics for 13 weeks. Mouse body weight, visceral adipose tissue (VAT), liver, and mammary glands (MG) were weighed at the end of the study. Fecal 16S rRNA sequencing was performed to determine gut bacterial microbiome populations. Collagen, macrophage, and monocyte chemoattractant protein-1 (MCP-1) in the VAT and MG tissue were examined by immunohistochemistry. Adipocyte diameter was measured in VAT. Immunohistochemistry of intestinal segments was used to examine villi length, muscularis thickness, and goblet cell numbers. We show that dietary interventions in Western diet-fed mice modulated % body weight gain, visceral adiposity, MG weight, gut microbial populations, and inflammation. Intervention strategies in both diets effectively reduced VAT and MG fibrosis, VAT and MG macrophages, adipocyte diameter, and VAT and MG MCP-1. Interventions also improved intestinal health parameters. In conclusion, dietary intervention with MGE and probiotics modulates several microbial, inflammatory, and metabolic factors reducing poor health outcomes associated with Western diet intake.

Early-life dietary exposures mediate persistent shifts in the gut microbiome and visceral fat metabolism.

In utero dietary exposures are linked to the development of metabolic syndrome in adult offspring. These dietary exposures can potentially impact gut microbial composition and offspring metabolic health. Female BALB/c mice were administered a lard, lard + flaxseed oil, high sugar, or control diet 4 wk before mating, throughout mating, pregnancy, and lactation. Female offspring were offered low-fat control diet at weaning. Fecal 16S sequencing was performed. Untargeted metabolomics was performed on visceral adipose tissue (VAT) of adult female offspring. Immunohistochemistry was used to determine adipocyte size, VAT collagen deposition, and macrophage content. Hippurate was administered via weekly intraperitoneal injections to low-fat and high-fat diet-fed female mice and VAT fibrosis and collagen 1A (COL1A) were assessed by immunohistochemistry. Lard diet exposure was associated with elevated body and VAT weight and dysregulated glucose metabolism. Lard + flaxseed oil attenuated these effects. Lard diet exposures were associated with increased adipocyte diameter and VAT macrophage count. Lard + flaxseed oil reduced adipocyte diameter and fibrosis compared with the lard diet. Hippurate-associated bacteria were influenced by lard versus lard + flax exposures that persisted to adulthood. VAT hippurate was increased in lard + flaxseed oil compared with lard diet. Hippurate supplementation mitigated VAT fibrosis pathology. Maternal high-fat lard diet consumption resulted in long-term metabolic and gut microbiome programming in offspring, impacting VAT inflammation and fibrosis, and was associated with reduced VAT hippurate content. These traits were not observed in maternal high-fat lard + flaxseed oil diet-exposed offspring. Hippurate supplementation reduced VAT fibrosis. These data suggest that detrimental effects of early-life high-fat lard diet exposure can be attenuated by dietary omega-3 polyunsaturated fatty acid supplementation.

Diet, obesity, and the gut microbiome as determinants modulating metabolic outcomes in a non-human primate model.

BACKGROUND: The objective of this study was to increase understanding of the complex interactions between diet, obesity, and the gut microbiome of adult female non-human primates (NHPs). Subjects consumed either a Western (n=15) or Mediterranean (n=14) diet designed to represent human dietary patterns for 31 months. Body composition was determined using CT, fecal samples were collected, and shotgun metagenomic sequencing was performed. Gut microbiome results were grouped by diet and adiposity. RESULTS: Diet was the main contributor to gut microbiome bacterial diversity. Adiposity within each diet was associated with subtle shifts in the proportional abundance of several taxa. Mediterranean diet-fed NHPs with lower body fat had a greater proportion of Lactobacillus animalis than their higher body fat counterparts. Higher body fat Western diet-fed NHPs had more Ruminococcus champaneliensis and less Bacteroides uniformis than their low body fat counterparts. Western diet-fed NHPs had significantly higher levels of Prevotella copri than Mediterranean diet NHPs. Western diet-fed subjects were stratified by P. copri abundance (P. copriHIGH versus P. copriLOW), which was not associated with adiposity. Overall, Western diet-fed animals in the P. copriHIGH group showed greater proportional abundance of B. ovatus, B. faecis, P. stercorea, P. brevis, and Faecalibacterium prausnitzii than those in the Western P. copriLOW group. Western diet P. copriLOW subjects had a greater proportion of Eubacterium siraeum. E. siraeum negatively correlated with P. copri proportional abundance regardless of dietary consumption. In the Western diet group, Shannon diversity was significantly higher in P. copriLOW when compared to P. copriHIGH subjects. Furthermore, gut E. siraeum abundance positively correlated with HDL plasma cholesterol indicating that those in the P. copriLOW population may represent a more metabolically healthy population. Untargeted metabolomics on urine and plasma from Western diet-fed P. copriHIGH and P. copriLOW subjects suggest early kidney dysfunction in Western diet-fed P. copriHIGH subjects. CONCLUSIONS: In summary, the data indicate diet to be the major influencer of gut bacterial diversity. However, diet and adiposity must be considered together when analyzing changes in abundance of specific bacterial taxa. Interestingly, P. copri appears to mediate metabolic dysfunction in Western diet-fed NHPs. Video abstract.

From the Table to the Tumor: The Role of Mediterranean and Western Dietary Patterns in Shifting Microbial-Mediated Signaling to Impact Breast Cancer Risk.

Diet is a modifiable component of lifestyle that could influence breast cancer development. The Mediterranean dietary pattern is considered one of the healthiest of all dietary patterns. Adherence to the Mediterranean diet protects against diabetes, cardiovascular disease, and cancer. Reported consumption of a Mediterranean diet pattern was associated with lower breast cancer risk for women with all subtypes of breast cancer, and a Western diet pattern was associated with greater risk. In this review, we contrast the available epidemiological breast cancer data, comparing the impact of consuming a Mediterranean diet to the Western diet. Furthermore, we will review the preclinical data highlighting the anticancer molecular mechanism of Mediterranean diet consumption in both cancer prevention and therapeutic outcomes. Diet composition is a major constituent shaping the gut microbiome. Distinct patterns of gut microbiota composition are associated with the habitual consumption of animal fats, high-fiber diets, and vegetable-based diets. We will review the impact of Mediterranean diet on the gut microbiome and inflammation. Outside of the gut, we recently demonstrated that Mediterranean diet consumption led to distinct microbiota shifts in the mammary gland tissue, suggesting possible anticancer effects by diet on breast-specific microbiome. Taken together, these data support the anti-breast-cancer impact of Mediterranean diet consumption.

Obesity-Linked Gut Microbiome Dysbiosis Associated with Derangements in Gut Permeability and Intestinal Cellular Homeostasis Independent of Diet.

This study aimed to determine the association between non-high-fat diet-induced obesity- (non-DIO-) associated gut microbiome dysbiosis with gut abnormalities like cellular turnover of intestinal cells, tight junctions, and mucin formation that can impact gut permeability. We used leptin-deficient (Lepob/ob) mice in comparison to C57BL/6J control mice, which are fed on identical diets, and performed comparative and correlative analyses of gut microbiome composition, gut permeability, intestinal structural changes, tight junction-mucin formation, cellular turnover, and stemness genes. We found that obesity impacted cellular turnover of the intestine with increased cell death and cell survival/proliferation gene expression with enhanced stemness, which are associated with increased intestinal permeability, changes in villi/crypt length, and decreased expression of tight junctions and mucus synthesis genes along with dysbiotic gut microbiome signature. Obesity-induced gut microbiome dysbiosis is also associated with abnormal intestinal organoid formation characterized with decreased budding and higher stemness. Results suggest that non-DIO-associated gut microbiome dysbiosis is associated with changes in the intestinal cell death versus cell proliferation homeostasis and functions to control tight junctions and mucous synthesis-regulating gut permeability.

Hidradenitis suppurativa: Mammographic and sonographic manifestations in two cases.

Hidradenitis suppurativa is a chronic debilitating disorder of the skin manifested by recurrent, painful, inflammatory, subcutaneous nodules. The lesions occur most commonly in the apocrine-gland-bearing skin sites such as the axillae and inguinal regions; they cause scarring and disfigurement from the formation of multiple abscesses and fistulous tracts within the skin. We report the radiologic manifestations of two cases of hidradenitis suppurativa in women who presented for breast imaging.

Clinical demand for chest/abdomen/pelvis anatomy following thoracic or lumbar spine CT.

The purpose of this study is to determine how often CT is repeated to obtain chest/abdomen/pelvis data outside the reconstructed field of view (FOV) on a prior spine CT. Radiology records of 1,239 consecutive thoracic and lumbar spine CT exams of 1,025 patients from January 1, 2006 to December 31, 2008 were retrospectively reviewed to identify patients who subsequently had CT studies of the chest, abdomen, and/or pelvis. The CT data were also evaluated for contrast enhancement, slice thickness, radiation dose, and reason for subsequent CT exam. Over 3 years, 290 of the 1,239 (24%) spine CT exams were followed by CT of the same anatomic region to evaluate extraspinal anatomy. The use or nonuse of contrast in these follow-up studies was the same as the preceding spine study in 91 cases, which were repeated on the same day (n = 37), within 7 days (n = 19), within 8-30 days (n = 15), or after 30 days (n = 20). Fourteen of 25 (56%) T spine CTs and 34 of 52 (65%) L spine CTs without contrast were followed by a chest CT or abdomen/pelvis CT without contrast within 7 days, respectively. Among 31 pediatric exams, 6 of 31 (19%) spine CTs were followed by a CT of the same anatomic region, all within 7 days. Reconstructing full FOV images of spine CT scans in addition to the standard coned down spine FOV may reduce redundant CT imaging and radiation dose.

Contrast-enhanced magnetic resonance angiography.

With technological advances in magnetic resonance angiography (MRA), spatial resolution of 1-mm perforating vessels can reliably be visualized and accurately located in reference to patients' anatomic landmarks without exposing patients to ionizing radiation or iodinated contrast, resulting in optimal perforator selection, improved flap design, and increased surgical efficiency. As their experience with MRA in breast reconstruction has increased, the authors have made changes to their MRA protocol that allow imaging of the vasculature in multiple donor sites (buttock, abdomen, and upper thigh) in one study. This article provides details of this experience with multiple donor site contrast-enhanced MRA.

Perforator flap magnetic resonance angiography for reconstructive breast surgery: a review of 25 deep inferior epigastric and gluteal perforator artery flap patients.

PURPOSE: To evaluate the accuracy of magnetic resonance angiography (MRA) for preoperative mapping of rectus and gluteal muscle perforating arteries prior to autologous flap breast reconstruction. MATERIALS AND METHODS: Preoperative MRA on 25 consecutive patients undergoing perforator artery-based autologous breast reconstruction was performed at 1.5 T using 3D liver accelerate volume acquisition (LAVA) of abdominal or gluteal regions acquired during injection of 20 mL of gadobenate dimeglumine with bolus timing optimized using MR fluoroscopy or SmartPrep. Perforator artery size and coordinates relative to umbilicus or top of gluteal crease on 3D MRA were compared to findings at surgery. Reconstructed breast volume estimates from MRA were also compared to weights at harvesting. RESULTS: In all, 132 perforator arteries were found at surgery to be located within 1 cm of the coordinates measured on MRA and were surgically verified to be suitable for flap perfusion. Surgery verified the arterial course and caliber through the rectus and gluteal muscles visualized on MRA in 48 of 49 arteries. Volume rendering of 3D MRA predicted a breast reconstruction volume with a mean difference of 47 g compared to measurements at harvesting. CONCLUSION: MRA accurately maps rectus and gluteal muscle perforator arteries for preoperative planning of autologous flaps for breast reconstruction.

Anatomic imaging of gluteal perforator flaps without ionizing radiation: seeing is believing with magnetic resonance angiography.

Preoperative imaging is essential for abdominal perforator flap breast reconstruction because it allows for preoperative perforator selection, resulting in improved operative efficiency and flap design. The benefits of visualizing the vasculature preoperatively also extend to gluteal artery perforator flaps. Initially, our practice used computed tomography angiography (CTA) to image the gluteal vessels. However, with advances in magnetic resonance imaging angiography (MRA), perforating vessels of 1-mm diameter can reliably be visualized without exposing patients to ionizing radiation or iodinated intravenous contrast. In our original MRA protocol to image abdominal flaps, we found the accuracy of MRA compared favorably with CTA. With our increased experience with MRA, we decided to use MRA to image gluteal flaps. Technical changes were made to the MRA protocol to improve image quality and extend the field of view. Using our new MRA protocol, we can image the vasculature of the buttock, abdomen, and upper thigh in one study. We have found that the spatial resolution of MRA is sufficient to accurately map gluteal perforating vessels, as well as provide information on vessel caliber and course. This article details our experience with preoperative imaging for gluteal perforator flap breast reconstruction.

Anatomic imaging of abdominal perforator flaps without ionizing radiation: seeing is believing with magnetic resonance imaging angiography.

The tremendous variability of the inferior epigastric arterial system makes accurate imaging of the vasculature of the anterior abdominal wall an essential component of optimal perforator selection. Preoperative imaging of the abdominal vasculature allows for preoperative perforator selection, resulting in improved operative efficiency and flap design. Abdominal wall perforators of 1-mm diameter can be reliably visualized without exposing patients to ionizing radiation or iodinated intravenous contrast through advances in magnetic resonance imaging angiography (MRA). In this study, MRA imaging was performed on 31 patients who underwent 50 abdominal flaps. For each flap, the location, relative to the umbilicus, of the three largest perforators on both the left and right sides of the abdomen was determined with MRA. Vessel diameter and anatomic course were also evaluated. Postoperatively, a survey was completed by the surgeon to assess the accuracy of the MRA with respect to the intraoperative findings. All perforators visualized on MRA were found at surgery (0% false-positive). In 2 of 50 flaps, the surgeon transferred a flap based upon a vessel not visualized on the MRA (4% false-negative). This article details our experience with MRA as a reliable preoperative imaging technique for abdominal perforator flap breast reconstruction.

Relation of aortic valve calcium to myocardial ischemic perfusion in individuals with a low coronary artery calcium score.

The absence of coronary artery calcium (CAC) is associated with minimal atherosclerosis. Nonetheless, morbid and mortal cardiovascular events occur in patients with low CAC. This study attempts to identify whether calcific deposits outside the coronary arteries or traditional cardiovascular risk variables are associated with myocardial ischemia in patients with low CAC scores. From 1998 to 2006, a total of 605 patients with an Agatston CAC score of 0 to 10 were referred for stress echocardiography or myocardial perfusion imaging. There was a low rate (1.2%) of myocardial ischemia. Seven of 303 patients (2.3%) had ischemia on perfusion imaging. Zero of 302 stress echocardiograms were abnormal. Traditional risk-factor analysis did not predict the presence of ischemia. No differences in age, gender, or self-reported hyperlipidemia, diabetes mellitus, tobacco use, hypertension, or family history of premature heart disease were noted. Contrary to previous belief, patients with myocardial ischemia were not younger or female. Aortic valve calcium (AVC) was associated with ischemia (p = 0.02), with a >10-fold likelihood of having ischemia detected by MPS versus those without AVC (20.0% vs 1.7%). In conclusion, a CAC score <10 is associated with a low rate of myocardial ischemia. AVC may identify a subset of patients who may be at higher risk.

Duke Twins Study of Memory in Aging in the NAS-NRC Twin Registry.

The Duke Twins Study of Memory in Aging is an ongoing, longitudinal study of cognitive change and dementia in the population-based National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry of World War II Male Veterans. The primary goal of this study has been to estimate the overall genetic and environmental contributions to dementia with a specific focus on Alzheimer's disease. An additional goal has been to examine specific genetic and environmental antecedents of cognitive decline and dementia. Since 1989, we have completed 4 waves of data collection. Each wave included a 2-phase telephone cognitive screening protocol, followed by an in-home standardized clinical assessment for those with suspected dementia. For many participants, we have obtained postmortem neuropathological confirmation of the diagnosis of dementia. In addition to data on cognition, we have also collected information on occupational history, medical history, medications and other lifetime experiences that may influence cognitive function in late life. We provide an overview of the study's methodology and describe the focus of recent research.