Reduction of trimethylamine N-oxide to trimethylamine by the human gut microbiota: supporting evidence for ‘metabolic retroversion’

Dietary sources of methylamines such as choline, trimethylamine (TMA), trimethylamine N-oxide (TMAO), phosphatidylcholine (PC) and carnitine are present in a number of foodstuffs, including meat, fish, nuts and eggs. It is recognized that the gut microbiota is able to convert choline to TMA in a fermentation-like process. Similarly, PC and carnitine are converted to TMA by the gut microbiota. It has been suggested that TMAO is subject to ‘metabolic retroversion’ in the gut (i.e. it is reduced to TMA by the gut microbiota, with this TMA being oxidized to produce TMAO in the liver). Sixty-six strains of human faecal and caecal bacteria were screened on solid and liquid media for their ability to utilize trimethylamine N-oxide (TMAO), with metabolites in spent media profiled by Proton Nuclear Magnetic Resonance (1H NMR) spectroscopy. Enterobacteriaceae produced mostly TMA from TMAO, with caecal/small intestinal isolates of Escherichia coli producing more TMA than their faecal counterparts. Lactic acid bacteria (enterococci, streptococci, bifidobacteria) produced increased amounts of lactate when grown in the presence of TMAO, but did not produce large amounts of TMA from TMAO. The presence of TMAO in media increased the growth rate of Enterobacteriaceae; while it did not affect the growth rate of lactic acid bacteria, TMAO increased the biomass of these bacteria. The positive influence of TMAO on Enterobacteriaceae was confirmed in anaerobic, stirred, pH-controlled batch culture fermentation systems inoculated with human faeces, where this was the only bacterial population whose growth was significantly stimulated by the presence of TMAO in the medium. We hypothesize that dietary TMAO is used as an alternative electron acceptor by the gut microbiota in the small intestine/proximal colon, and contributes to microbial population dynamics upon its utilization and retroversion to TMA, prior to absorption and secondary conversion to TMAO by hepatic flavin-containing monooxygenases. Our findings support the idea that oral TMAO supplementation is a physiologically-stable microbiota-mediated strategy to deliver TMA at the gut barrier.

Production systems and supplier selection: a multi-phase process model

Purpose: This paper presents a combined multi-phase supplier selection model. The process repeatedly revisits the criteria and sourcing decision as the development process continues. This enables a structured adoption of product and production system innovation from strategic suppliers, where previously the literature purely focuses on product innovation or cost reduction. Design/methodology/approach: The authors adopted an embedded researcher style, inductive, qualitative case study of an industrial supply cluster comprising a focal automotive company and its interaction with three different strategic stamping suppliers. Findings: Our contribution is the multi-phased production and product innovation process. This is an advance from traditional supplier selection and also an extension of ideas of supplier-located product development as it includes production system development, and complements the literature on working with strategic suppliers. Specifically, we explicitly articulate the previously unreported issue of whether a supplier chosen for its innovation capabilities at the start of the new product development process will also be the most appropriate supplier during the production system development phase, when an ability to work collaboratively may be the most important attribute, or in the large-scale production phase when an ability to manufacture at low unit cost may be most important. Originality/value: The paper identifies a multi-phase approach to tendering within a fixed body of strategic suppliers which seeks to identify the optimum technological and process decisions as well as the traditional supplier sourcing choice. These areas have not been combined before and generate a valuable approach for firms to adopt as well as for researchers to extend our understanding of a highly complex process.

Business Process Modelling based on formal temporal theory with an application to hospital patient flows

Existing Workflow Management Systems (WFMSs) follow a pragmatic approach. They often use a proprietary modelling language with an intuitive graphical layout. However the underlying semantics lack a formal foundation. As a consequence, analysis issues, such as proving correctness i.e. soundness and completeness, and reliable execution are not supported at design level. This project will be using an applied ontology approach by formally defining key terms such as process, sub-process, action/task based on formal temporal theory. Current business process modelling (BPM) standards such as Business Process Modelling Notation (BPMN) and Unified Modelling Language (UML) Activity Diagram (AD) model their constructs with no logical basis. This investigation will contribute to the research and industry by providing a framework that will provide grounding for BPM to reason and represent a correct business process (BP). This is missing in the current BPM domain, and may result in reduction of the design costs and avert the burden of redundant terms used by the current standards. A graphical tool will be introduced which will implement the formal ontology defined in the framework. This new tool can be used both as a modelling tool and at the same time will serve the purpose of validating the model. This research will also fill the existing gap by providing a unified graphical representation to represent a BP in a logically consistent manner for the mainstream modelling standards in the fields of business and IT. A case study will be conducted to analyse a catalogue of existing ‘patient pathways’ i.e. processes, of King’s College Hospital NHS Trust including current performance statistics. Following the application of the framework, a mapping will be conducted, and new performance statistics will be collected. A cost/benefits analysis report will be produced comparing the results of the two approaches.

A general framework for Business Process Modelling (BPM) based on Formal Temporal Theory with an application to Hospital Patient flows

Existing Workflow Management Systems (WFMSs) follow a pragmatic approach. They often use a proprietary modelling language with an intuitive graphical layout. However the underlying semantics lack a formal foundation. As a consequence, analysis issues, such as proving correctness i.e. soundness and completeness, and reliable execution are not supported at design level. This project will be using an applied ontology approach by formally defining key terms such as process, sub-process, action/task based on formal temporal theory. Current business process modelling (BPM) standards such as Business Process Modelling Notation (BPMN) and Unified Modelling Language (UML) Activity Diagram (AD) model their constructs with no logical basis. This investigation will contribute to the research and industry by providing a framework that will provide grounding for BPM to reason and represent a correct business process (BP). This is missing in the current BPM domain, and may result in reduction of the design costs and avert the burden of redundant terms used by the current standards. A graphical tool will be introduced which will implement the formal ontology defined in the framework. This new tool can be used both as a modelling tool and at the same time will serve the purpose of validating the model. This research will also fill the existing gap by providing a unified graphical representation to represent a BP in a logically consistent manner for the mainstream modelling standards in the fields of business and IT. A case study will be conducted to analyse a catalogue of existing ‘patient pathways’ i.e. processes, of King’s College Hospital NHS Trust including current performance statistics. Following the application of the framework, a mapping will be conducted, and new performance statistics will be collected. A cost/benefits analysis report will be produced comparing the results of the two approaches.