Dietary approaches for normalizing dysbiosis induced by high-fat, obesogenic diets.

PURPOSE OF REVIEW: Given the world-wide problem of obesity, this review considers what types of dietary changes can be utilized to minimize the adverse effects of an obesogenic diet on the intestinal microbiota. RECENT FINDINGS: In rodents fed high-fat diets containing lard or Western blend fats to induce obesity, switching to high-fat diets formulated to contain higher amounts of fiber or fiber-containing foods, plant extracts, omega-3 fatty acids or whole grains has beneficial effects on body weight, metabolic alterations, and the intestinal microbiota. Several studies show that the intestinal microbiota has a role in mediating the beneficial health effects of these dietary factors. Many aspects of the microbiota observed in animals when healthful dietary components were added to the feed have also been observed in humans who follow healthful dietary patterns. SUMMARY: The data shows that specific foods and macronutrients can normalize the obesity-associated microbiota and improve metabolic health. These findings support the design of dietary interventions that would allow individuals to focus on diet quality independently of weight loss to mitigate the adverse sequelae of obesity.

Proton Pump Inhibitor Use and Obesity-Associated Cancer in the Women's Health Initiative.

Proton pump inhibitors (PPIs) have off-target activity on fatty acid synthase (FASN), a critical enzyme in energy balance and cancer growth. We evaluated risk of common obesity-related cancers: breast, colorectal (CRC), and endometrial, with use of PPI and histamine-2 receptor antagonists (H2RA) in 124,931 postmenopausal women enrolled in the Women's Health Initiative. Incident cancer cases were physician-adjudicated. Cox proportional hazards models were used to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI) for cancer incidence after year 3. There were 7956 PPI ever users and 9398 H2RA only users. Ever use of either PPI or H2RA was not associated with risk of breast cancer (n = 9186) nor risk of endometrial cancer (n = 1231). The risk of CRC (n = 2280) was significantly lower in PPI users (HR = 0.75, 95% CI = 0.61-0.92), but not in H2RA users (HR = 1.13, 95% CI = 0.97-1.31). The association of PPI use with CRC was apparent regardless of BMI or NSAID use, and was stronger with longer PPI duration (p = 0.006) and potency (p = 0.005). The findings that PPI use, but not H2RA use, demonstrate an inverse dose-response relationship with risk of CRC is consistent with preclinical data showing FASN inhibition prevents colon cancer progression and supports a role of PPI in CRC prevention.

Changes in Serum, Red Blood Cell, and Colonic Fatty Acids in a Personalized Omega-3 Fatty Acid Supplementation Trial.

This study evaluated changes in fatty acids from sera, red blood cells, and colonic biopsies from a phase Ib clinical trial of personalized ω-3 fatty acid dosing in 47 healthy volunteers. The trial aimed to reduce colonic prostaglandin E2 (PGE2), a pro-inflammatory product of arachidonic acid (AA) oxidation. The personalized doses ranged 2-10 grams/day (54% eicosapentaenoic acid, EPA, 24% other ω-3 fatty acids). In colon, increases in ω-3 highly unsaturated fatty acids (HUFA) and EPA:AA ratios each were correlated with decreases in PGE2. Changes in either colonic EPA:AA ratios or ω-3 HUFA were significantly correlated with changes in the same fatty acid measures in red blood cells or serum. The only blood-based measure significantly correlated with changes in colonic PGE2 was change in red blood cell ω-3 HUFA (ρ = -0.39), and the increase in red blood cell ω-3 HUFA was significantly greater in participants who had at least a median reduction in colonic PGE2 vs. those who did not. In summary, fatty acid changes in blood did reflect fatty acid changes in the colon, but additional factors will be needed for optimizing dosing models that seek to predict the anti-inflammatory effects of ω-3 fatty acids on the colon.

A New Score for Quantifying Adherence to a Cancer-Preventive Mediterranean Diet.

Herein a Mediterranean Cancer Preventive Diet Score (MCAP Score) is proposed to quantify adherence to both traditional Mediterranean fat intakes and the current dietary recommendations for cancer prevention. The scoring uses research-backed cutoff values, unlike other scores that are based on a population-specific median value. The MCAP score awards positive points for seven preventive food categories, including Mediterranean fats (monounsaturated fats, ω-3 fatty acids) associated with reduced adiposity, and negative points for four food categories associated with increased cancer risk, including ultra-processed foods. In a randomized trial of 120 persons at increased risk of colon cancer, the baseline MCAP Score averaged seven of 20 possible points. Counseling for a Healthy Diet or a Mediterranean Diet improved the score to either 11 or 13 points, respectively, and the highest score observed in any individual was 20 points. The MCAP Score was correlated with serum carotenoids and serum ω-3 fatty acids, and improvements in the score were associated with weight loss over six months of study. The MCAP Score is therefore proposed as a new method to assess adherence to a Mediterranean type of diet for cancer prevention using absolute criteria that will facilitate comparisons of dietary intakes across studies.

Gestational exposure to high fat diets and bisphenol A alters metabolic outcomes in dams and offspring, but produces hepatic steatosis only in dams.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. Perinatal development is a critical window for altered, lifelong health trajectory, and evidence supports the role of perinatal programming in chronic metabolic diseases. To examine the impact of diet and bisphenol A (BPA) on the developmental trajectory of NAFLD in offspring, we exposed dams from pre-gestation through lactation to a human-relevant dose of oral BPA coupled with intake of high fat Western or Mediterranean-style diets. We assessed hepatic steatosis by quantifying hepatic triglycerides (TGs) and metabolic health by measuring body weight, relative organ weights, and serum hormone levels in dams and offspring at postnatal day 10 (PND10) and 10-months of age. In dams, consumption of the Western or Mediterranean diet increased hepatic TGs 1.7-2.4-fold, independent of BPA intake. Among offspring, both perinatal diet and BPA exposure had a greater impact on metabolic outcomes than on hepatic steatosis. At PND10, serum leptin levels were elevated 2.6-4.8-fold in pups exposed to the Mediterranean diet, with a trend for sex-specific effects on body and organ weights. At 10-months, sex-specific increases in organ weight and hormone levels were observed in mice perinatally exposed to Western + BPA or Mediterranean + BPA. These findings suggest lifestage-specific interaction of perinatal exposures to experimental diets and BPA on offspring metabolic health without effects on NAFLD later in life. Importantly, alterations in dam phenotype by diet and BPA exposure appear to impact offspring health trajectory, emphasizing the need to define dam diet in assessing effects of environmental exposures on offspring health.

Association of meal timing with dietary quality in a Serbian population sample.

BACKGROUND: The world-wide adoption of Western lifestyles and eating patterns is associated with adverse effects on nutrient intakes. Here we evaluated the relationships between timing of meals and diet quality in Serbia, a Balkan country with a traditional eating pattern that includes the largest meal of the day as a late lunch. METHODS: A dietary survey was done in the Republic of Serbia using a nationally-representative sample of 74 children and 260 non-pregnant adults. Nutrient intakes were calculated from two 24-h recalls. A Dietary Quality Score (DQS) enumerated how many European Union (EU) Science Hub recommendations were met for fruit and vegetables, fiber, saturated fat, sodium, and sugar. We evaluated whether the timing of dietary intakes is associated with DQS and body mass index. RESULTS: The dietary intakes of children ages 10-17 and adults were similar and were high in total fat intake, with an average of 40% of energy from fat. Mean fruit and vegetable intakes of 473 g/day in adults exceeded the minimal EU recommendation. The most worrisome aspects of the Serbian diet were high intakes of saturated fat, sugar and sodium. Lunch was the meal with the highest mean content of energy, followed by breakfast and dinner, and the average time for lunch was 15:15. Consumption of a higher percentage of calories before 16:00 in adults was associated with higher fruit and vegetable intakes and with higher DQS. The subgroup of adults consuming their largest meal after 20:00 had a lower mean age, more men, and a larger percentage was employed outside of the home. There were no associations of meal timing with BMI, but the prevalence of obesity in this population sample was only 13%. CONCLUSIONS: These results indicate that an earlier meal pattern, and especially consuming the largest meal of the day earlier in the day, was associated with better quality diets. Public health efforts are needed to preserve nutrient intakes as the population shifts away from the traditional Serbian eating pattern. Long-term, deterioration of nutrient intakes could contribute to the increasing rates of obesity that have been observed in Serbia and world-wide.

An Adaptive Bayesian Design for Personalized Dosing in a Cancer Prevention Trial.

INTRODUCTION: In biomarker-driven clinical trials, translational strategies typically involve moving findings from animal experiments to human trials. Typically, the translation is static, using a fixed model derived from animal experiments for the duration of the trial. Bayesian designs, capable of incorporating information external to the experiment, provide a dynamic translational strategy. This article demonstrates an example of such a dynamic Bayesian strategy in a clinical trial. METHODS: This study explored the effect of a personalized dose of fish oil for reducing prostaglandin E2, an inflammatory marker linked to colorectal cancer. A Bayesian design was implemented for the dose-finding algorithm that adaptively updated a dose-response model derived from a previously completed animal study during the clinical trial. In the initial stages of the trial, the dose-response model parameters were estimated from the rodent data. The model was updated following a Bayesian algorithm after data on every 10‒15 subjects were obtained until the model stabilized. Subjects were enrolled in the study between 2013 and 2015, and the data analysis was carried out in 2016. RESULTS: The 3 dosing models were used for groups of 16, 15, and 15 subjects. The mean target dose significantly decreased from 6.63 g/day (Model 1) to 4.06 g/day (Model 3) (p=0.001). Compared with the static strategy of dosing with a single model, the dynamic modeling reduced the dose significantly by about 1.38 g/day on average. CONCLUSIONS: A Bayesian design was effective in adaptively revising the dosing algorithm, resulting in a lower pill burden. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT01860352.

How Does Obesity Drive Human Carcinogenesis? Challenges in Dissecting the Mechanisms of Adipose-Epithelial Signaling.

Obesity is the second leading environmental association with cancer risk; yet, the mechanisms by which obesity drives carcinogenesis are poorly understood. The paper published in this issue of Cancer Prevention Research by Holowatyj and colleagues explores the mechanisms of human visceral adipose-epithelial signaling using samples collected at surgery in patients with invasive colorectal cancer. They identify pathway intermediates potentially involved in the regulation of fibrosis, inflammation, glycosis, and epithelial-mesenchymal transition in neoplastic tissue. 'Omics-based profiling of perioperative human biosamples has potential for inherent biases (preoperative and intraoperative drug therapies, hydration, dynamics, inflammatory response to surgical intervention) and appropriate control samples are difficult to identify and collect. Solutions to this dilemma may include strategies to identify patients undergoing similar surgical procedures but who are without neoplasms, for example, patients with gynecologic problems, abdominal exploration for suspected appendicitis, symptoms or resection of gall stone disease or undergoing bariatric surgery. As the field continues to grow, studies incorporating robust statistical analyses, validation of findings in diverse cohorts, and public data sharing will be essential to identify biological pathways linking obesity and carcinogenesis to be further interrogated using focused, hypothesis-driven approaches.See related article by Holowatyj et al., p. 817.

Dietary polyunsaturated fatty acids modulate adipose secretome and is associated with changes in mammary epithelial stem cell self-renewal.

Chronic low-grade adipose inflammation, characterized by aberrant adipokine production and pro-inflammatory macrophage activation/polarization is associated with increased risk of breast cancer. Adipocyte fatty acid composition is influenced by dietary availability and may regulate adipokine secretion and adipose inflammation. After feeding F344 rats for 20 weeks with a Western diet or a fish oil-supplemented diet, we cultured primary rat adipose tissue in a three-dimensional explant culture and collected the conditioned medium. The rat adipose tissue secretome was assayed using the Proteome Profiler Cytokine XL Array, and adipose tissue macrophage polarization (M1/M2 ratio) was assessed using the iNOS/ARG1 ratio. We then assessed the adipokine's effects upon stem cell self-renewal using primary human mammospheres from normal breast mammoplasty tissue. Adipose from rats fed the fish oil diet had an ω-3:ω-6 fatty acid ratio of 0.28 compared to 0.04 in Western diet rats. The adipokine profile from the fish oil-fed rats was shifted toward adipokines associated with reduced inflammation compared to the rats fed the Western diet. The M1/M2 macrophage ratio decreased by 50% in adipose of fish oil-fed rats compared to that from rats fed the Western diet. Conditioned media from rats fed the high ω-6 Western diet increased stem cell self-renewal by 62%±9% (X¯%±SD) above baseline compared to only an 11%±11% increase with the fish oil rat adipose. Modulating the adipokine secretome with dietary interventions therefore may alter stromal-epithelial signaling that plays a role in controlling mammary stem cell self-renewal.

Increases in Colonic Bacterial Diversity after ω-3 Fatty Acid Supplementation Predict Decreased Colonic Prostaglandin E2 Concentrations in Healthy Adults.

BACKGROUND: The intestinal microbiome is an important determinant of inflammatory balance in the colon that may affect response to dietary agents. OBJECTIVE: This is a secondary analysis of a clinical trial, the Fish Oil Study, to determine whether interindividual differences in colonic bacteria are associated with variability in the reduction of colonic prostaglandin E2 (PGE2) concentrations after personalized supplementation with ω-3 (n-3) fatty acids. METHODS: Forty-seven healthy adults (17 men, 30 women, ages 26-75 y) provided biopsy samples of colonic mucosa and luminal stool brushings before and after personalized ω-3 fatty acid supplementation that was based on blood fatty acid responses. Samples were analyzed using 16S ribosomal RNA sequencing. The data analyses focused on changes in bacterial community diversity. Linear regression was used to evaluate factors that predict a reduction in colonic PGE2. RESULTS: At baseline, increased bacterial diversity, as measured by the Shannon and Inverse Simpson indexes in both biopsy and luminal brushing samples, was positively correlated with dietary fiber intakes and negatively correlated with fat intakes. Dietary supplementation with ω-3 fatty acids increased the Yue and Clayton community dis-similarity index between the microbiome in luminal brushings and colon biopsy samples post-supplementation (P = 0.015). In addition, there was a small group of individuals with relatively high Prevotella abundance who were resistant to the anti-inflammatory effects of ω-3 fatty acid supplementation. In linear regression analyses, increases in diversity of the bacteria in the luminal brushing samples, but not in the biopsy samples, were significant predictors of lower colonic PGE2 concentrations post-supplementation in models that included baseline PGE2, baseline body mass index, and changes in colonic eicosapentaenoic acid-to-arachidonic acid ratios. The changes in bacterial diversity contributed to 6-8% of the interindividual variance in change in colonic PGE2 (P = 0.001). CONCLUSIONS: Dietary supplementation with ω-3 fatty acids had little effect on intestinal bacteria in healthy humans; however, an increase in diversity in the luminal brushings significantly predicted reductions in colonic PGE2. This trial was registered at www.clinicaltrials.gov as NCT01860352.

A Mediterranean diet does not alter plasma trimethylamine N-oxide concentrations in healthy adults at risk for colon cancer.

An elevated circulating level of trimethylamine N-oxide (TMAO) has been identified as a risk factor for numerous diseases, including cardiovascular disease (CVD) and colon cancer. TMAO is formed from trimethylamine (TMA)-precursors such as choline via the combined action of the gut microbiota and liver. We conducted a Mediterranean diet intervention that increased intakes of fiber and changed intakes of many other foods containing fat to increase the relative amount of mono-unsaturated fats in the diet. The Mediterranean diet is associated with reduced risks of chronic diseases and might counteract the pro-inflammatory effects of increased TMAO formation. Therefore, the purpose of this study was to determine if the Mediterranean diet would reduce TMAO concentrations. Fasting TMAO concentrations were measured before and after six-months of dietary intervention in 115 healthy people at increased risk for colon cancer. No significant changes in plasma TMAO or in the ratios of TMAO to precursor compounds were found in either the Mediterranean group or the comparison group that followed a Healthy Eating diet. TMAO concentrations exhibited positive correlations with age and markers of metabolic health. TMAO concentrations were not associated with circulating cytokines, but the relative abundance of Akkermansia mucinophilia in colon biopsies was modestly and inversely correlated with baseline TMAO, choline, and betaine serum concentrations. These results suggest that broad dietary pattern intervention over six months may not be sufficient for reducing TMAO concentrations in an otherwise healthy population. Disruption of the conversion of dietary TMA to TMAO should be the focus of future studies.

Improving Blood Pressure Among African Americans With Hypertension Using a Mobile Health Approach (the MI-BP App): Protocol for a Randomized Controlled Trial.

BACKGROUND: African Americans shoulder significant disparities related to hypertension (HTN), which is a serious public health problem in the city of Detroit, Michigan, where more than 80% of the population is African American. Connectivity through smartphones, use of home blood pressure (BP) monitoring, and newly developed mobile health (mHealth) interventions can facilitate behavioral changes and may improve long-term self-care for chronic conditions, but implementation of a combined approach utilizing these methods has not been tested among African American patients with uncontrolled HTN. Since African Americans are more likely than other racial or ethnic subgroups to utilize the emergency department (ED) for ambulatory care, this presents an opportunity to intervene on a population that is otherwise difficult to reach. OBJECTIVE: The MI-BP app aims to reduce health disparities related to HTN in the community by employing a user-centered intervention focused on self-BP monitoring, physical activity, reduced sodium intake, and medication adherence. We seek to test the efficacy of MI-BP, an mHealth app for HTN self-management, on BP control (primary aim), physical activity, sodium intake, and medication adherence (secondary aim) in African Americans with HTN. This study also seeks to evaluate the cost-effectiveness of MI-BP when compared with usual care methods. METHODS: This is a 1-year randomized controlled trial that will recruit individuals who have uncontrolled HTN from 2 EDs in the city of Detroit, with a planned sample size of 396 randomized participants. To be eligible for inclusion, potential participants must be African American, 25 to 70 years old, previously diagnosed with HTN, have a smartphone compatible with MI-BP, and have uncontrolled BP at triage and on repeat measurement at least 1-hour post triage vitals. Once a participant is deemed eligible, all study procedures and subsequent follow-up visits (8 in total) are conducted at the Wayne State University Clinical Research Service Center. We seek to determine the effect of MI-BP on BP for 1 year (using BP control and mean systolic BP as coprimary outcomes and physical activity, sodium intake, and medication adherence as secondary outcomes) compared with usual care controls. RESULTS: Recruitment for this study began in January 2018. The study will continue through 2021. CONCLUSIONS: As the first of its kind conducted in an ED setting, MI-BP was designed to document the efficacy and acceptability of a multicomponent mHealth approach to help African Americans with uncontrolled BP modify their lifestyle to better manage their HTN. We expect to lay the foundation to sustainably reduce HTN-related health disparities through better integration of multiple behavior self-monitoring and improve outcomes for those who traditionally rely on the ED for chronic disease care. TRIAL REGISTRATION: ClinicalTrials.gov NCT02360293; http://clinicaltrials.gov/ct2/show/NCT02360293. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/12601.

Higher baseline expression of the PTGS2 gene and greater decreases in total colonic fatty acid content predict greater decreases in colonic prostaglandin-E2 concentrations after dietary supplementation with ω-3 fatty acids.

This study evaluated whether mRNA expression of major genes regulating formation of prostaglandin (PG)E2 in the colon and colonic fatty acid concentrations are associated with the reduction in colonic mucosal PGE2 after dietary supplementation with omega-3 (ω-3) fatty acids. Supplementation with ω-3 fatty acids was done for 12 weeks using personalized dosing that was expected to reduce colonic PGE2 by 50%. In stepwise linear regression models, the ω-3 fatty acid dose and baseline BMI explained 16.1% of the inter-individual variability in the fold change of colonic PGE2 post-supplementation. Increases in mRNA gene expression after supplementation were, however, modest and were not associated with changes in PGE2. When baseline expression of PTGS1, PTGS2 and HPGD genes was included in the linear regression model containing dose and BMI, only PTGS2, the gene coding for the inducible form cyclooxygenase, was a significant predictor. Higher relative expression of PTGS2 predicted greater decreases in colonic PGE2, accounting for an additional 13.6% of the inter-individual variance. In the final step of the regression model, greater decreases in total colonic fatty acid concentrations predicted greater decreases in colonic PGE2, contributing to an additional 18.7% of the variance. Overall, baseline BMI, baseline expression of PTGS2 and changes in colonic total fatty acids together accounted for 48% of the inter-individual variability in the change in colonic PGE2. This is consistent with biochemical data showing that fatty acids which are not substrates for cyclooxygenases can activate cyclooxygenase-2 allosterically. Further clinical trials are needed to elucidate the factors that regulate the fatty acid milieu of the human colon and how this interacts with key lipid metabolizing enzymes. Given the central role of PGE2 in colon carcinogenesis, these pathways may also impact on colon cancer prevention by other dietary and pharmacological approaches.

Effect of prenatal EPA and DHA on maternal and umbilical cord blood cytokines.

BACKGROUND: Investigators have hypothesized that omega-3 fatty acid supplementation may modulate the immune response. However, available evidence is conflicting. We performed this study to investigate the effect of prenatal eicosapentaenoic acid (EPA)- and docosahexaenoic acid (DHA)-rich fish oil supplementation on maternal and fetal cytokine production. METHODS: This study is a secondary analysis of a randomized controlled trial designed to assess whether prenatal EPA- or DHA-rich fish oil supplementation would prevent perinatal depressive symptoms among women at risk. Enrolled participants received EPA-rich fish oil (1060 mg EPA plus 274 mg DHA), DHA-rich fish oil (900 mg DHA plus 180 mg EPA) or soy oil placebo. Maternal venous blood was collected at enrollment (12-20 weeks gestation) and after supplementation (34-36 weeks gestation). Umbilical cord blood was collected at delivery. We analyzed stored plasma specimens for 16 human cytokines using multiplex immunoassays. Maternal and cord blood cytokine levels were compared among the treatment groups. Associations of serum DHA and EPA with maternal and cord blood cytokines were explored via regression analysis. RESULTS: We enrolled 126 women, of whom 118 completed the trial. Prenatal supplementation with EPA-rich fish oil significantly lowered maternal IL6, IL15, and TNFα concentrations. However, supplementation with DHA-rich fish oil had no significant effect on maternal cytokine profiles. Maternal serum DHA fraction was significantly associated with IL1α, and maternal serum DHA and EPA fractions were significantly associated with IL 10 concentrations after supplementation. Compared with placebo, supplementation with EPA- or DHA-rich fish oils had no significant effect on cord blood cytokine concentrations. CONCLUSIONS: Prenatal supplementation with EPA-rich fish oil significantly reduced levels of several inflammatory cytokines in maternal plasma, while prenatal DHA-rich fish oil had no significant effect on cytokine concentrations. Supplementation with EPA- and DHA- rich fish oil had no significant effect on umbilical cord blood cytokine concentrations. TRIAL REGISTRATION: Clinical Trial Registration: registration number NCT00711971 7/7/2008.

Colonic Mucosal Bacteria Are Associated with Inter-Individual Variability in Serum Carotenoid Concentrations.

BACKGROUND: Relatively high serum carotenoid levels are associated with reduced risks of chronic diseases, but inter-individual variability in serum carotenoid concentrations is modestly explained by diet. The bacterial community in the colon could contribute to the bioaccessibility of carotenoids by completing digestion of plant cells walls and by modulating intestinal permeability. OBJECTIVE: To evaluate whether colonic bacterial composition is associated with serum and colon carotenoid concentrations. DESIGN: The study was a randomized dietary intervention trial in healthy individuals who were at increased risk of colon cancer. Colon mucosal biopsy samples were obtained before and after 6 months of intervention without prior preparation of the bowels. PARTICIPANTS/SETTING: Participants were recruited from Ann Arbor, MI, and nearby areas from July 2007 to November 2010. Biopsy data were available from 88 participants at baseline and 82 participants after 6 months. METHODS: Study participants were randomized to counseling for either a Mediterranean diet or a Healthy Eating diet for 6 months. RESULTS: At baseline, bacterial communities in biopsy samples from study participants in the highest vs the lowest tertile of total serum carotenoid levels differed by several parameters. Linear discriminant analysis effect size identified 11 operational taxonomic units that were significantly associated with higher serum carotenoid levels. In linear regression analyses, three of these accounted for an additional 12% of the variance in serum total carotenoid concentrations after including body mass index, smoking, and dietary intakes in the model. These factors together explained 36% of the inter-individual variance in serum total carotenoid concentrations. The bacterial community in the colonic mucosa, however, was resistant to change after dietary intervention with either a Mediterranean diet or Healthy Eating diet, each of which doubled fruit and vegetable intakes. CONCLUSIONS: The colonic mucosal bacterial community was associated with serum carotenoid concentrations at baseline but was not appreciably changed by dietary intervention.

The Anti-inflammatory Effect of Personalized Omega-3 Fatty Acid Dosing for Reducing Prostaglandin E2 in the Colonic Mucosa Is Attenuated in Obesity.

This clinical trial developed a personalized dosing model for reducing prostaglandin E2 (PGE2) in colonic mucosa using ω-3 fatty acid supplementation. The model utilized serum eicosapentaenoic acid (EPA, ω-3):arachidonic acid (AA, ω-6) ratios as biomarkers of colonic mucosal PGE2 concentration. Normal human volunteers were given low and high ω-3 fatty acid test doses for 2 weeks. This established a slope and intercept of the line for dose versus serum EPA:AA ratio in each individual. The slope and intercept was utilized to calculate a personalized target dose that was given for 12 weeks. This target dose was calculated on the basis of a model, initially derived from lean rodents, showing a log-linear relationship between serum EPA:AA ratios and colonic mucosal PGE2 reduction. Bayesian methods allowed addition of human data to the rodent model as the trial progressed. The dosing model aimed to achieve a serum EPA:AA ratio that is associated with a 50% reduction in colonic PGE2 Mean colonic mucosal PGE2 concentrations were 6.55 ng/mg protein (SD, 5.78) before any supplementation and 3.59 ng/mg protein (SD, 3.29) after 12 weeks of target dosing. In secondary analyses, the decreases in PGE2 were significantly attenuated in overweight and obese participants. This occurred despite a higher target dose for the obese versus normal weight participants, as generated by the pharmacodynamic predictive model. Large decreases also were observed in 12-hydroxyicosatetraenoic acids, and PGE3 increased substantially. Future biomarker-driven dosing models for cancer prevention therefore should consider energy balance as well as overall eicosanoid homeostasis in normal tissue. Cancer Prev Res; 10(12); 729-37. ©2017 AACR.

Fatty acid and lipidomic data in normal and tumor colon tissues of rats fed diets with and without fish oil.

Data is provided to show the detailed fatty acid and lipidomic composition of normal and tumor rat colon tissues. Rats were fed either a Western fat diet or a fish oil diet, and half the rats from each diet group were treated with chemical carcinogens that induce colon cancer (azoxymethane and dextran sodium sulfate). The data show total fatty acid profiles of sera and of all the colon tissues, namely normal tissue from control rats and both normal and tumor tissues from carcinogen-treated rats, as obtained by gas chromatography with mass spectral detection. Data from lipidomic analyses of a representative subset of the colon tissue samples is also shown in heat maps generated from hierarchical cluster analysis. These data display the utility lipidomic analyses to enhance the interpretation of dietary feeding studies aimed at cancer prevention and support the findings published in the companion paper (Effects of fish oil supplementation on prostaglandins in normal and tumor colon tissue: modulation by the lipogenic phenotype of colon tumors, Djuric et al., 2017 [1]).

Delivery of Health Coaching by Medical Assistants in Primary Care.

BACKGROUND: Health coaching is potentially a practical method to assist patients in achieving and maintaining healthy lifestyles. In health coaching, the coach partners with the patient, helping patients discover their own strengths, challenges, and solutions. METHODS: Two medical assistants were provided with brief training. The 12-week program consisted of telephone coaching with in-person visits at the beginning and end of the program. Coaching targeted improvements in diet, physical activity, and/or sleep habits using a self-care planning form. RESULTS: A total of 82 subjects enrolled in the program, 72% completed 8 weeks and 49% completed 12 weeks. Subjects who completed assessments at 12 weeks had significant weight loss despite the fact that weight loss was not a study goal. There also were improvements in diet and physical activity. Subject who completed the study were highly satisfied with the program and felt that health coaching should be available in all family medicine clinics. The main barrier providers voiced was remembering to refer patients. The medical providers indicated high satisfaction with the study and valued having coaching available for their patients. CONCLUSIONS: Medical assistants can be trained to assist patients with lifestyle changes that are associated with improved health and weight control.

Effects of fish oil supplementation on prostaglandins in normal and tumor colon tissue: modulation by the lipogenic phenotype of colon tumors.

Dietary fish oils have potential for prevention of colon cancer, and yet the mechanisms of action in normal and tumor colon tissues are not well defined. Here we evaluated the impact of the colonic fatty acid milieu on the formation of prostaglandins and other eicosanoids. Distal tumors in rats were chemically induced to model inflammatory colonic carcinogenesis. After 21 weeks of feeding with either a fish oil diet containing an eicosapentaenoic acid/ω-6 fatty acid ratio of 0.4 or a Western fat diet, the relationships between colon fatty acids and prostaglandin E2 (PGE2) concentrations were evaluated. PGE2 is a key proinflammatory mediator in the colon tightly linked with the initiation and progression of colon cancer. The fish oil vs. the Western fat diet resulted in reduced total fatty acid concentrations in serum but not in colon. In the colon, the effects of the fish oil on fatty acids differed in normal and tumor tissue. There were distinct lipodomic patterns consistent with a lipogenic phenotype in tumors. In tumor tissue, the eicosapentaenoic acid/arachidonic acid ratio, cyclooxygenase-2 expression and the mole percent of saturated fatty acids were significant predictors of inter-animal variability in colon PGE2 after accounting for diet. In normal tissues from either control rats or carcinogen-treated rats, only diet was a significant predictor of colon PGE2. These results show that the fatty acid milieu can modulate the efficacy of dietary fish oils for colon cancer prevention, and this could extend to other preventive agents that function by reducing inflammatory stress.

Gas chromatography-mass spectrometry analysis of effects of dietary fish oil on total fatty acid composition in mouse skin.

Altering the fatty acid (FA) composition in the skin by dietary fish oil could provide therapeutic benefits. Although it has been shown that fish oil supplementation enhances EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) abundance in the skin, comprehensive skin FA profiling is needed. We established a gas chromatography-mass spectrometry method, which allows precise quantification of FA profile using small (<24 mm2 for mice and <12 mm2 for humans) skin specimens that can be readily obtained from live mice and humans. We determined mouse skin FA composition after 2, 4 and 8 weeks of consuming a control diet or a diet supplemented with fish oil. Fish oil markedly enhanced EPA and DHA in mouse skin within 2 weeks, and this increase plateaued after 4 weeks. The FA composition in mouse skin was different from that of serum, indicating that skin has homeostatic control of FA metabolism. Mice fed the control diet designed to simulate Western human diet displayed similar skin FA composition as that of humans. The present study presents a validated method for FA quantification that is needed to investigate the mechanisms of actions of dietary treatments in both mouse and human skin.