Association of Habitual Intake of Probiotic Supplements and Yogurt with Characteristics of the Gut Microbiome in the Multiethnic Cohort Adiposity Phenotype Study.

Consumption of probiotics and/or yogurt could be a solution for restoring the balance of the gut microbiota. This study examined associations of regular intake of probiotic supplements or yogurt with the gut microbiota among a diverse population of older adults (N=1,861; 60-72 years). Fecal microbial composition was obtained from 16S rRNA gene sequencing (V1-V3 region).

Personalized Nutrition Using Microbial Metabolite Phenotype to Stratify Participants and Non-Invasive Host Exfoliomics Reveal the Effects of Flaxseed Lignan Supplementation in a Placebo-Controlled Crossover Trial.

High-fiber plant foods contain lignans that are converted to bioactive enterolignans, enterolactone (ENL) and enterodiol (END) by gut bacteria. Previously, we conducted an intervention study to gain mechanistic insight into the potential chemoprotective effects of flaxseed lignan supplementation (secoisolariciresinol diglucoside; SDG) compared to a placebo in 42 men and women. Here, we expand on these analyses to further probe the impact of the microbial metabolite phenotype on host gene expression in response to lignan exposure.

Recruitment and Retention of Healthy, Postmenopausal Women of African and European Ancestry: Results from a Dietary Intervention with Repeated Biospecimen Collections.

Recruitment of minority participants to clinical trials, especially studies without therapeutic intent, has been historically challenging. This study describes barriers to and successes of recruitment and retention strategies to dietary studies. A flaxseed study was conducted in healthy, postmenopausal women of African ancestry (AA) and European ancestry (EA) to assess associations between gut microbial community composition and host metabolism (NCT01698294).

Associations of the Dietary Inflammatory Index with total adiposity and ectopic fat through the gut microbiota, LPS, and C-reactive protein in the Multiethnic Cohort-Adiposity Phenotype Study.

Background: Mechanisms linking a proinflammatory diet to obesity remain under investigation. The ability of diet to influence the gut microbiome (GM) in creating chronic low-grade systemic inflammation provides a plausible connection to adiposity.

Objectives: Assess whether any associations seen between the Energy-Adjusted Dietary Inflammatory Index (E-DII score), total fat mass, visceral adipose tissue (VAT), or liver fat (percentage volume) operated through the GM or microbial related inflammatory factors, in a multiethnic cross-sectional study.

Associations of the gut microbiome with hepatic adiposity in the Multiethnic Cohort Adiposity Phenotype Study.

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for liver cancer and prevalence varies by ethnicity. Along with genetic and lifestyle factors, the gut microbiome (GM) may contribute to NAFLD and its progression to advanced liver disease. Our cross-sectional analysis assessed the association of the GM with hepatic adiposity among African American, Japanese American, White, Latino, and Native Hawaiian participants in the Multiethnic Cohort.

Long-term association between diet quality and characteristics of the gut microbiome in the multiethnic cohort study.

As past usual diet quality may affect gut microbiome (GM) composition, we examined the association of the Healthy Eating Index (HEI)-2015 assessed 21 and 9 years before stool collection with measures of fecal microbial composition in a subset of the Multiethnic Cohort. A total of 5936 participants completed a validated quantitative FFQ (QFFQ) at cohort entry (Q1, 1993-1996), 5280 at follow-up (Q3, 2003-2008) and 1685 also at a second follow-up (Adiposity Phenotype Study (APS), 2013-2016). All participants provided a stool sample in 2013-2016.

The Gut Microbiome Is Associated with Circulating Dietary Biomarkers of Fruit and Vegetable Intake in a Multiethnic Cohort.

Background: Results from observational studies suggest high diet quality favorably influences the human gut microbiome. Fruit and vegetable consumption is often a key contributor to high diet quality.

Objective: To evaluate measures of gut bacterial diversity and abundance in relation to serum biomarkers of fruit and vegetable intake.

The gut microbiome and type 2 diabetes status in the Multiethnic Cohort.

Background: The gut microbiome may play a role in inflammation associated with type 2 diabetes (T2D) development. This cross-sectional study examined its relation with glycemic status within a subset of the Multiethnic Cohort (MEC) and estimated the association of circulating bacterial endotoxin (measured as plasma lipopolysaccharide-binding protein (LBP)) with T2D, which may be mediated by C-reactive protein (CRP).

Methods: In 2013-16, cohort members from five ethnic groups completed clinic visits, questionnaires, and stool and blood collections.

Enterolignan Production in a Flaxseed Intervention Study in Postmenopausal US Women of African Ancestry and European Ancestry.

Lignans are phytochemicals studied extensively as dietary factors in chronic disease etiology. Our goal was to examine associations between the gut microbiota and lignan metabolism and whether these associations differ by ethnicity. We conducted a flaxseed (FS) dietary intervention in 252 healthy, postmenopausal women of African ancestry (AA) and European ancestry (EA).

Limited effects of long-term daily cranberry consumption on the gut microbiome in a placebo-controlled study of women with recurrent urinary tract infections.

Background: Urinary tract infections (UTIs) affect 15 million women each year in the United States, with > 20% experiencing frequent recurrent UTIs. A recent placebo-controlled clinical trial found a 39% reduction in UTI symptoms among recurrent UTI sufferers who consumed a daily cranberry beverage for 24 weeks. Using metagenomic sequencing of stool from a subset of these trial participants, we assessed the impact of cranberry consumption on the gut microbiota, a reservoir for UTI-causing pathogens such as Escherichia coli, which causes > 80% of UTIs.

Effect of a Flaxseed Lignan Intervention on Circulating Bile Acids in a Placebo-Controlled Randomized, Crossover Trial.

Plant lignans and their microbial metabolites, e.g., enterolactone (ENL), may affect bile acid (BA) metabolism through interaction with hepatic receptors.

Gut Microbial Protein Expression in Response to Dietary Patterns in a Controlled Feeding Study: A Metaproteomic Approach.

Although the gut microbiome has been associated with dietary patterns linked to health, microbial metabolism is not well characterized. This ancillary study was a proof of principle analysis for a novel application of metaproteomics to study microbial protein expression in a controlled dietary intervention. We measured the response of the microbiome to diet in a randomized crossover dietary intervention of a whole-grain, low glycemic load diet (WG) and a refined-grain, high glycemic load diet (RG).

Associations of plasma trimethylamine N-oxide, choline, carnitine, and betaine with inflammatory and cardiometabolic risk biomarkers and the fecal microbiome in the Multiethnic Cohort Adiposity Phenotype Study.

Background: Trimethylamine N-oxide (TMAO), a compound derived from diet and metabolism by the gut microbiome, has been associated with several chronic diseases, although the mechanisms of action are not well understood and few human studies have investigated microbes involved in its production.

Objectives: Our study aims were 1) to investigate associations of TMAO and its precursors (choline, carnitine, and betaine) with inflammatory and cardiometabolic risk biomarkers; and 2) to identify fecal microbiome profiles associated with TMAO.

Methods: We conducted a cross-sectional analysis using data collected from 1653 participants (826 men and 827 women, aged 60-77 y) in the Multiethnic Cohort Study.

Diet and Gut Microbes Act Coordinately to Enhance Programmed Cell Death and Reduce Colorectal Cancer Risk.

Diet is an important risk factor for colorectal cancer (CRC), and several dietary constituents implicated in CRC are modified by gut microbial metabolism. Microbial fermentation of dietary fiber produces short-chain fatty acids, e.g.

Modulation of Gut Microbiota by Glucosamine and Chondroitin in a Randomized, Double-Blind Pilot Trial in Humans.

Glucosamine and chondroitin (G&C), typically taken for joint pain, are among the most frequently used specialty supplements by US adults. More recently, G&C have been associated with lower incidence of colorectal cancer in human observational studies and reduced severity of experimentally-induced ulcerative colitis in rodents. However, little is known about their effects on colon-related physiology.

Proteomic Analysis of Plasma Reveals Fat Mass Influences Cancer-Related Pathways in Healthy Humans Fed Controlled Diets Differing in Glycemic Load.

Increased adiposity and diets high in glycemic load (GL) are associated with increased risk of many chronic diseases including cancer. Using plasma from 80 healthy individuals [40 men/40 women, 29 with DXA-derived low fat mass (FM) and 51 with high FM] in a randomized cross-over-controlled feeding trial and arrays populated with 3,504 antibodies, we measured plasma proteins collected at baseline and end of each of two 28-day controlled diets: a low GL diet high in whole grains, legumes, fruits, and vegetables (WG) and a high GL diet high in refined grains and added sugars (RG). Following univariate testing for proteins differing by diet, we evaluated pathway-level involvement.

Fecal Microbial Diversity and Structure Are Associated with Diet Quality in the Multiethnic Cohort Adiposity Phenotype Study.

Background: Variation in gut microbial community structure is partly attributed to variations in diet. A priori dietary indexes capture diet quality and have been associated with chronic disease risk.

Objectives: The aim of this study was to examine the association of diet quality, as assessed by the Healthy Eating Index, Alternative Healthy Eating Index-2010, alternate Mediterranean Diet, and the Dietary Approaches to Stop Hypertension Trial, with measures of fecal microbial community structure assessed in the Adiposity Phenotype Study (APS), an ethnically diverse study population with varied food intakes.

Colonic mucosal and exfoliome transcriptomic profiling and fecal microbiome response to a flaxseed lignan extract intervention in humans.

Background: Microbial metabolism of lignans from high-fiber plant foods produces bioactive enterolignans, such as enterolactone (ENL) and enterodiol (END). Enterolignan exposure influences cellular pathways important to cancer risk and is associated with reduced colon tumorigenesis in animal models and lower colorectal cancer risk in humans.

Objectives: The aim of this study was to test the effects of a flaxseed lignan supplement (50 mg secoisolariciresinol diglucoside/d) compared with placebo on host gene expression in colon biopsies and exfoliated colonocyte RNA in feces and fecal microbial community composition, and to compare responses in relation to ENL excretion.

Temporal Variability and Stability of the Fecal Microbiome: The Multiethnic Cohort Study.

Background: Measurement reliability and biological stability need to be considered when developing sampling protocols for population-based fecal microbiome studies.

Methods: Stool samples were collected biannually over a 2-year period and sequenced for the V1-V3 region of the 16S rRNA gene in 50 participants from the Multiethnic Cohort Study. We evaluated the temporal stability of the fecal microbiome on a community level with permutational multivariate analysis of variance (PERMANOVA), as well as on taxa and diversity measures with intraclass correlation coefficients.

The canine gut microbiome is associated with higher risk of gastric dilatation-volvulus and high risk genetic variants of the immune system.

Background: Large and giant dog breeds have a high risk for gastric dilatation-volvulus (GDV) which is an acute, life-threatening condition. Previous work by our group identified a strong risk of GDV linked to specific alleles in innate and adaptive immune genes. We hypothesize that variation in the genes of the immune system act through modulation of the gut microbiome, or through autoimmune mechanisms, or both, to predispose dogs to this condition.

Circulating bile acids in healthy adults respond differently to a dietary pattern characterized by whole grains, legumes and fruits and vegetables compared to a diet high in refined grains and added sugars: A randomized, controlled, crossover feeding study.

Objective: The effects of diets high in refined grains on biliary and colonic bile acids have been investigated extensively. However, the effects of diets high in whole versus refined grains on circulating bile acids, which can influence glucose homeostasis and inflammation through activation of farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5), have not been studied.

Materials And Methods: We conducted a secondary analysis from a randomized controlled crossover feeding trial (NCT00622661) in 80 healthy adults (40 women/40 men, age 18-45 years) from the greater Seattle Area, half of which were normal weight (BMI 18.

Plasma lipopolysaccharide-binding protein and colorectal cancer risk: a nested case-control study in the Multiethnic Cohort.

Background: Lipopolysaccharide (LPS), an endotoxin found on the outer cell wall of Gram-negative bacteria, increases inflammatory response signaling and may play a role in the pathogenesis of several adverse outcomes, including inflammatory bowel diseases, cardiovascular disease, and cancer. While LPS is hypothesized to be associated with colorectal carcinogenesis, there are relatively few human studies which have examined this association.

Methods: We examined the association between colorectal cancer (CRC) and plasma lipopolysaccharide-binding protein (LBP), a marker of LPS, in 1,638 participants (819 CRC cases and 819 controls) matched on multiple factors, including age, sex, and race/ethnicity, from the Multiethnic Cohort study.

Associations between gastric dilatation-volvulus in Great Danes and specific alleles of the canine immune-system genes DLA88, DRB1, and TLR5.

OBJECTIVE To determine whether specific alleles of candidate genes of the major histocompatibility complex (MHC) and innate immune system were associated with gastric dilatation-volvulus (GDV) in Great Danes. ANIMALS 42 healthy Great Danes (control group) and 39 Great Danes with ≥ 1 GDV episode. PROCEDURES Variable regions of the 2 most polymorphic MHC genes (DLA88 and DRB1) were amplified and sequenced from the dogs in each group.