Publications

Introduction: Dietary patterns high in healthy plant foods play an important role in modulating the gut microbiome and promoting cardiometabolic health. Little is known on the diet-gut microbiome relationship in U.S. Hispanics/Latinos, who have a high burden of obesity and diabetes. Hypothesis: Three healthy dietary patterns - the alternate Mediterranean diet (aMED), the Healthy Eating Index (HEI)-2015, and the healthful Plant-based Diet Index (hPDI), will be associated with gut microbiome composition in U.S. Hispanic/Latino adults, and healthy-diet-related species will be related to favorable cardiometabolic traits. Methods: HCHS/SOL is a multi-site community-based cohort. At baseline (2008-11), diet was assessed via two 24-hr recalls. Shotgun sequencing was performed on stool samples collected in 2014-17 (n=2,985). Analysis of Compositions of Microbiomes 2 (ANCOM2) was used to identify associations of dietary pattern scores with gut microbiome species and functions, adjusting for sociodemographic, behavioral, and clinical covariates. Results: Better diet quality according to multiple healthy dietary patterns was associated with higher abundance of species from class Clostridia, including [Eubacterium] eligens , Butyrivibrio crossotus , and Lachnospiraceae bacterium TF01-11 , as well as functions related to fiber fermentation (e.g. pyruvate:ferredoxin oxidoreductase). Poorer diet quality was associated with higher abundance of Acidaminococcus intestini , as well as functions of manganese/iron transport, adhesin protein transport, and nitrate reduction. Healthy diet pattern-enriched Clostridia species were related to more favorable cardiometabolic traits such as lower triglycerides ( Figure 1 ). Conclusions: Healthy dietary patterns in this population are associated with a fiber-fermenting gut microbiome, consistent with previous studies in other racial/ethnic groups. Gut microbiota may be involved in the beneficial effect of higher diet quality on cardiometabolic disease risk.

BACKGROUND Due to the rapidly increasing availability of metabolomics data in prospective studies, an update of the meta evidence on metabolomics and type 2 diabetes risk is warranted. PURPOSE To conduct an updated systematic review and meta-analysis of plasma, serum, and urine metabolite markers and incident type 2 diabetes. DATA SOURCES We searched PubMed and Embase until 6 March 2021. STUDY SELECTION We selected prospective observational studies where investigators used high-throughput techniques to investigate the relationship between plasma, serum, or urine metabolites and incident type 2 diabetes. DATA EXTRACTION Baseline metabolites per-SD risk estimates and 95% CIs for incident type 2 diabetes were extracted from all eligible studies. DATA SYNTHESIS A total of 61 reports with 71,196 participants and 11,771 type 2 diabetes cases/events were included in the updated review. Meta-analysis was performed for 412 metabolites, of which 123 were statistically significantly associated (false discovery rate–corrected P < 0.05) with type 2 diabetes risk. Higher plasma and serum levels of certain amino acids (branched-chain, aromatic, alanine, glutamate, lysine, and methionine), carbohydrates and energy-related metabolites (mannose, trehalose, and pyruvate), acylcarnitines (C4-DC, C4-OH, C5, C5-OH, and C8:1), the majority of glycerolipids (di- and triacylglycerols), (lyso)phosphatidylethanolamines, and ceramides included in meta-analysis were associated with higher risk of type 2 diabetes (hazard ratio 1.07–2.58). Higher levels of glycine, glutamine, betaine, indolepropionate, and (lyso)phosphatidylcholines were associated with lower type 2 diabetes risk (hazard ratio 0.69–0.90). LIMITATIONS Substantial heterogeneity (I2 > 50%, τ2 > 0.1) was observed for some of the metabolites. CONCLUSIONS Several plasma and serum metabolites, including amino acids, lipids, and carbohydrates, are associated with type 2 diabetes risk.

Our data suggest that greater physical activity is modestly associated with favorable levels of cardiometabolic and endocrine biomarkers, where the strongest associations were found with accelerometer-measured physical activity. These associations may be only partially mediated through BMI, further supporting the role of physical activity in the reduction of cardiometabolic and endocrine disease risk, independent of adiposity.

Introduction: Recent studies reported inverse associations between circulating levels of n-6 polyunsaturated fatty acids (PUFAs) and type 2 diabetes (T2D) risk, although whether intake of these fatty acids is associated T2D risk remains to be elucidated. Hypothesis: We examined the hypothesis that long-term intake of n-6 PUFAs, especially linoleic acid (LA), is associated with lower T2D risk. Methods: Diet was assessed using validated food-frequency questionnaires every 4 years in women participating in Nurses' Health Study (NHS, n=83,648) and NHSII (n=88,610), and men participating in the Health Professionals Follow-Up Study (n=41,771). Incident T2D was identified by self-report and confirmed by a supplemental questionnaire. Results: N-6 PUFAs accounted for 4.7-6.8% total energy on average, and 98% of n-6 PUFA intake was from LA. We identified 18,442 T2D cases during 4.93 million person-years of follow-up. In multivariate-adjusted models, HRs (95%CIs) of T2D comparing extreme quintiles (high vs low) were 0.92 (0.88, 0.97; P trend =0.01) for LA intake, and 1.14 (1.08, 1.20; P trend <0.001) for arachidonic acid (AA) intake. It was further estimated that T2D risk were 6% lower when SFAs (2% of total energy) were iso-calorically replaced by LA intake ( table below). For each 2% energy from LA intake, T2D risk was 17% lower for iso-calorically replacing trans fats, and 4% lower for iso-calorically replacing total carbohydrates, and refined carbohydrates (All P values <0.05). These findings remained after adjusting for baseline BMI instead updated BMI, further adjusting for incident hypertension and hypercholesterolemia, or placing a 4-year lag between dietary assessments and disease incidence. Conclusion: Higher LA consumption is associated with a lower T2D risk, especially when substituting for SFAs, trans fats, or refined carbohydrates. AA mainly comes from poultry and meats, and is associated with higher T2D risk.

For many types of cells, behavior in two-dimensional (2D) culture differs from that in three-dimensional (3D) culture.Among biologists, 2D culture on treated plastic surfaces is currently the most popular method for cell culture.In 3D, no analogous standard method-one that is similarly convenient, flexible, and reproducible-exists.This paper describes a softlithographic method to encapsulate cells in 3D gel objects (modules) in a variety of simple shapes (cylinders, crosses, rectangular prisms) with lateral dimensions between 40 and 1000 mm, cell densities of 10 5 -10 8 cells/cm 3 , and total volumes between 1610 27 and 8610 24 cm 3 .By varying (i) the initial density of cells at seeding, and (ii) the dimensions of the modules, the number of cells per module ranged from 1 to 2500 cells.Modules were formed from a range of standard biopolymers, including collagen, Matrigel TM , and agarose, without the complex equipment often used in encapsulation.The small dimensions of the modules allowed rapid transport of nutrients by diffusion to cells at any location in the module, and therefore allowed generation of modules with cell densities near to those of dense tissues (10 8 -10 9 cells/cm 3 ).This modular method is based on soft lithography and requires little special equipment; the method is therefore accessible, flexible, and well suited to (i) understanding the behavior of cells in 3D environments at high densities of cells, as in dense tissues, and (ii) developing applications in tissue engineering.

Degradable microparticles have broad utility as vehicles for drug delivery and form the basis of several therapies approved by the US Food and Drug Administration. Conventional emulsion-based methods of manufacturing produce particles with a wide range of diameters (and thus kinetics of release) in each batch. This paper describes the fabrication of monodisperse, drug-loaded microparticles from biodegradable polymers using the microfluidic flow-focusing (FF) devices and the drug-delivery properties of those particles. Particles are engineered with defined sizes, ranging from 10 microm to 50 microm. These particles are nearly monodisperse (polydispersity index = 3.9%). A model amphiphilic drug (bupivacaine) is incorporated within the biodegradable matrix of the particles. Kinetic analysis shows that the release of the drug from these monodisperse particles is slower than that from conventional methods of the same average size but a broader distribution of sizes and, most importantly, exhibit a significantly lower initial burst than that observed with conventional particles. The difference in the initial kinetics of drug release is attributed to the uniform distribution of the drug inside the particles generated using the microfluidic methods. These results demonstrate the utility of microfluidic FF for the generation of homogenous systems of particles for the delivery of drugs.