Trimethylamine and trimethylamine N-oxide, a flavin-containing monooxygenase 3 (FMO3)-mediated host-microbiome metabolic axis implicated in health and disease

Flavin-containing monooxygenase 3 (FMO3) is known primarily as an enzyme involved in the metabolism of therapeutic drugs. However, on a daily basis we are exposed to one of the most abundant substrates of the enzyme, trimethylamine, which is released from various dietary components by the action of gut bacteria. FMO3 converts the odorous trimethylamine to non-odorous trimethylamine N-oxide, which is excreted in urine. Impaired FMO3 activity gives rise to the inherited disorder primary trimethylaminuria. Affected individuals cannot produce trimethylamine N-oxide and, consequently, excrete large amounts of trimethylamine. A dysbiosis in gut bacteria can give rise to secondary trimethylaminuria. Recently, there has been much interest in FMO3 and its catalytic product trimethylamine N-oxide. This is because trimethylamine N-oxide has been implicated in various conditions affecting health, including cardiovascular disease, reverse cholesterol transport and glucose and lipid homeostasis. In this review, we consider the dietary components that can give rise to trimethylamine, the gut bacteria involved in the production of trimethylamine from dietary precursors, the metabolic reactions by which bacteria produce and utilize trimethylamine and the enzymes that catalyze the reactions. Also included is information on bacteria that produce trimethylamine in the oral cavity and vagina, two key microbiome niches that can influence health. Finally, we discuss the importance of the trimethylamine/trimethylamine N-oxide microbiome-host axis in health and disease, considering factors that affect bacterial production and host metabolism of trimethylamine, the involvement of trimethylamine N-oxide and FMO3 in disease and the implications of the host-microbiome axis for management of trimethylaminuria

Identification of flavin-containing monooxygenase 5 (FMO5) as a regulator of glucose homeostasis and a potential sensor of gut bacteria

We have previously identified flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic aging. The aim of the present study was to investigate the role of FMO5 in glucose homeostasis and the impact of diet and gut flora on the phenotype of mice in which the Fmo5 gene has been disrupted (Fmo5−/− mice). In comparison with wild-type (WT) counterparts, Fmo5−/− mice are resistant to age-related changes in glucose homeostasis and maintain the higher glucose tolerance and insulin sensitivity characteristic of young animals. When fed a high-fat diet, they are protected against weight gain and reduction of insulin sensitivity. The phenotype of Fmo5−/− mice is independent of diet and the gut microbiome and is determined solely by the host genotype. Fmo5−/− mice have metabolic characteristics similar to those of germ-free mice, indicating that FMO5 plays a role in sensing or responding to gut bacteria. In WT mice, FMO5 is present in the mucosal epithelium of the gastrointestinal tract where it is induced in response to a high-fat diet. In comparison with WT mice, Fmo5−/− mice have fewer colonic goblet cells, and they differ in the production of the colonic hormone resistin-like molecule β. Fmo5−/− mice have lower concentrations of tumor necrosis factor α in plasma and of complement component 3 in epididymal white adipose tissue, indicative of improved inflammatory tone. Our results implicate FMO5 as a regulator of body weight and of glucose disposal and insulin sensitivity and, thus, identify FMO5 as a potential novel therapeutic target for obesity and insulin resistance

Politics Matters: Dynamics of Inter-organizational Networks among Immigrant Associations

We model the dynamics of the two-mode network among directors and boards of voluntary associations, using a stochastic actor-based model, SIENA [12], including the structural effects proposed in [6], and considering the political orientation of associations as a covariate. Using data from [14], we compare the evolution of interlocks among Turkish associations in two European capitals, and explain the noticeable difference in structure by looking at statistically significant differences among the estimated effects.info:eu-repo/semantics/publishe

Effect of Flavin-Containing Monooxygenase Genotype, Mouse Strain, and Gender on Trimethylamine N-oxide Production, Plasma Cholesterol Concentration, and an Index of Atherosclerosis

The objectives of the study were to determine the contribution, in mice, of members of the flavin-containing monooxygenase (FMO) family to the production of trimethylamine N-oxide (TMAO), a potential proatherogenic molecule, and whether, under normal dietary conditions, differences in TMAO production were associated with changes in plasma cholesterol concentration or with an index of atherosclerosis (Als). Concentrations of urinary trimethylamine (TMA) and TMAO and of plasma cholesterol were measured in 10-week-old male and female C57BL/6J and CD-1 mice and in mouse lines deficient in various Fmo genes (Fmo1(-/-), 2(-/-), 4(-/-) and Fmo5(-/-) ). In females most TMA N-oxygenation was catalyzed by FMO3, but in both genders 11-12% of TMA was converted to TMAO by FMO1. Gender-, Fmo genotype- and strain-related differences in TMAO production were accompanied by opposite effects on plasma cholesterol concentration. In all cases, plasma cholesterol was negatively correlated with TMAO production. Fmo genotype had no effect on Als. Als was positively correlated with TMAO in male C57BL/6J, Fmo1(-/-), 2(-/-), 4(-/-) and Fmo5(-/-) mice, but not in females, which produced substantially higher TMAO concentrations. The positive correlation in males was dependent on the inclusion of Fmo1(-/-), 2(-/-), 4(-/-) mice. In contrast, in male wild-type C57BL/6J and CD-1 mice Als was negatively correlated with TMAO. Thus, although a correlation between Als and TMAO was observed for a particular combination of mouse strain/gender/genotype this was not generally the case. Our results, therefore, indicate that under normal dietary conditions TMAO does not increase plasma cholesterol or act as a proatherogenic molecule

Agro-materials : a bibliographic review

Facing the problems of plastic recycling and fossil resources exhaustion, the use of biomass to conceive new materials appears like a reasonable solution. Two axes of research are nowadays developed : on the one hand the synthesis of biodegradable plastics, whichever the methods may be, on the other hand the utilization of raw biopolymers, which is the object of this paper. From this perspective, the “plastic” properties of natural polymers, the caracteristics of the different classes of polymers, the use of charge in vegetable matrix and the possible means of improving the durability of these agro-materials are reviewed

A Test of Rank-Dependent Utility in the Context of Ambiguity

Experimental investigations of non-expected utility have primarily concentrated on decision under risk (probability triangles). The literature suggests, however, that ambiguity is one of the main causes for deviations from expected utility (EU). This article investigates the descriptive performance of rank-dependent utility (RDU) in the context of choice under ambiguity. We use the axiomatic difference between RDU and EU to critically test RDU against EU. Surprisingly, the RDU model does not provide any descriptive improvement over EU. Our data suggest other framing factors that do provide descriptive improvements over EU

Genetic Influences on Cortical Regionalization in the Human Brain

SummaryAnimal data demonstrate that the development of distinct cortical areas is influenced by genes that exhibit highly regionalized expression patterns. In this paper, we show genetic patterning of cortical surface area derived from MRI data from 406 adult human twins. We mapped genetic correlations of areal expansion between selected seed regions and all other cortical locations, with the selection of seed points based on results from animal studies. “Marching seeds” and a data-driven, hypothesis-free, fuzzy-clustering approach provided convergent validation. The results reveal strong anterior-to-posterior graded, bilaterally symmetric patterns of regionalization, largely consistent with patterns previously reported in nonhuman mammalian models. Broad similarities in genetic patterning between rodents and humans might suggest a conservation of cortical patterning mechanisms, whereas dissimilarities might reflect the functionalities most essential to each species

The political dimension: added value for cross-cultural analysis:Nozawa and Smits, two CEO's and their public statements

Work-related cultural differences, which were familiarized by scholars such as Hall and Hofstede, offer important concepts to help us understand various forms of cooperation and communication. However, the predominant focus of cultural analysis on collectivistic harmony prevents us from gaining an understanding of strategy and conflict. In an attempt to grasp how conflicts are handled, a political analysis can provide new insights. This is illustrated by a comparative study of two CEOs who gave public statements concerning management failure: Shouhei Nozawa of Yamaichi and Paul Smits of KPN. Their statements were strikingly different in several ways, but the classical insights of cross-cultural analysis can only partly explain the differences. This is where political analysis comes in, focusing on interest relationships, responsibilities and virtues, tactics and strategy