Hepatitis C virus (HCV) infection is one of the major causes of liver morbidity and mortality worldwide. While effective therapies are now available, if eradication of this virus is to be achieved globally, an effective vaccine is still necessary. During hepatitis C virus (HCV) infection, broadly neutralizing antibody (bNAb) responses targeting E1E2 envelope glycoproteins are generated in many individuals. It is unclear if these antibodies play a protective or a pathogenic role during chronic infection or if they could prevent infection or reinfection with the virus. I investigated the presence and clinical associations of bNAb responses in three cohorts of individuals infected with or exposed to HCV infection. One with chronic HCV infection at differing disease states, one with chronic HCV infection at an early disease state and one group of individuals at high risk of HCV exposure who remained uninfected by conventional testing. I also studied bNAb responses in an individual from a HCV-HIV co-infected cohort who experienced spontaneous clearance of HCV after a post-therapy relapse (‘secondary spontaneous clearance’). I found a proportion of individuals when exposed to or infected with HCV produce a polyclonal bNAb response which may contribute to viral clearance in some cases. Host genetics and the ability to target multiple neutralising epitopes on the envelope protein are associated with such responses, although resistance mutations to bNAbs do exist in vivo. The presence of bNAbs is associated with lower levels of liver fibrosis. Using next generation sequencing technology in the study of B cell receptors in HCV infection revealed subtle changes in the B cell repertoire on HCV infection, this technology may be used in future to gain insight into the generation of bNAb responses.

Tissue engineering and regenerative medicine is a constantly evolving field of science that directs the use of cells to repair damaged or diseased tissue. Currently, stem cells are the most widely used source of cells due to their inherent characteristics of self-renewal and differentiation. However, stem cell regenerative therapies are still lacking, upon removal from the body, stem cell grow dysplastically towards unwanted lineages, compounded by their limited number makes the therapeutic potential of these cells difficult to obtain. These problems are due to the lack of knowledge of the underlying systems and mechanisms of phenotypical commitment through differentiation. In an attempt to circumvent these problems, scientists have begun the construction of dynamic surfaces, that is, surfaces that mimic the constantly evolving and changing environment in which stem cells reside in the body, known as the niche. These biomimetic strategies aim to reproduce the physical architecture, chemical composition and plasticity of the in vivo environment in vitro. This physical architecture can provide the cells with behavioural cues, mainly through transmembrane receptors known as integrins which link the extracellular matrix to the cytoskeleton; and therefore convey physical architecture of the environment to the cell. Scientists consciously design biomimetic systems to incorporate integrin binding ligands such as the adhesive tripeptide arginine-glycine-aspartic acid (RGD). The chemical composition of the niche depends on the in vivo milieu, and the needs of the body at this specified time. More specifically, mesenchymal stem cells reside in a variety of niches, with the bone marrow being a prime example. Upon osteogenesis, many chemical signals are delivered to this niche, with arguably the strongest osteogenic signal from bone morphogenetic protein 2 (BMP-2). This growth factor can activate osteogenic genes within the mesenchymal stem cell and predetermine differentiation of the cell towards an osteoblastic fate. In this work, we have developed a genetically engineered non-pathogenic bacteria, Lactococcus lactis to display the III7-10 fragment of fibronectin to allow mammalian cell integrin adhesion. This fragment contains two important sequences, the RGD adhesive tripeptide and the synergy sequence proline-histidine-serine-arginine-asparagine (PHSRN). RGD allows the mammalian cells to interact with the bacteria through promiscuous integrin attachment. The PHSRN sequence binds synergistically with RGD to some integrins, such as α5β1. These bacteria have also been modified to express the osteogenic growth factor, BMP-2 to direct mesenchymal stem cell differentiation towards an osteoblastic fate. These bacteria readily form spontaneous two-dimensional biofilms on a variety of surfaces, and can therefore act as a living interface between the synthetic surface below and the mammalian cells seeded above. The results of this thesis demonstrate that Lactococcus lactis can be used as a successful dynamic surface to control the adhesion, proliferation and differentiation of mesenchymal stem cells. Mesenchymal stem cells seeded over BMP-2 secreting Lactococcus lactis demonstrate decreased cell proliferation at short time points and increased osteoblastic markers at longer time points. Further to this, the interface has been made dynamic by making the bacteria inducible, that is, BMP-2 can be expressed in a temporal manner, and at different concentrations to finely tailor specific protein production. In the future, this system can be further exploited to express or deliver almost any protein or small molecule that can aid in the development of new tissues from their progenitor cells. As demonstrated, these proteins can both be secreted into the medium or displayed as cell wall bound proteins; and can also be constitutively or inducibly expressed. This interface, based on non-pathogenic bacteria establishes a new paradigm in surface functionalisation for regenerative medicine applications.

No description available.

In June 2001 the title ‘chiropractor’ came to be protected under British law and those who called themselves chiropractors attained a position of increased legitimacy within British society. Yet the details of chiropractic’s journey to statutory recognition have not been thoroughly explored in contemporary literature. The origins and development of chiropractic in Britain have received meagre attention from historical scholars. This thesis uses a neo-Weberian approach to explore the history of chiropractic in Britain through the lens of ‘professionalisation’. It investigates the emergence of chiropractic in Britain, and details how and why chiropractic developed in the way that it did, assessing the significance of processes and events in respect to chiropractic’s professionalisation, and examining intra- and inter-occupational tensions. The thesis is primarily a product of documentary research, but is also informed by interviews undertaken to provide oral testimonies. Although the origins of chiropractic are usually traced back to the 1890s, to Davenport, Iowa, and to the practice of Daniel David Palmer, it is argued in this thesis that it is misleading to claim that chiropractic was ‘discovered’ by Daniel Palmer, or that chiropractic in Britain was entirely an ‘import’ from the United States. Instead, chiropractic’s origins were complex and multifarious and form part of a broader history of manipulative practices. With regard to the development of chiropractic in Britain, chiropractic’s history is intertwined with that of osteopathy, and has involved medicalisation. This study demonstrates that through the course of its evolution chiropractic was subject to processes that can usefully be described in terms of professionalisation, sharing features in common with the professionalisation of other occupational groups described in historical and sociological literature. Even so, chiropractors did not attain the social presence or cultural authority of archetypal professionals such as medical doctors or lawyers. Although protection of title was achieved, many problems have remained, including divisions within the occupation.

In the early days of PKU, micronutrient deficiencies, undernutrition and growth failure were common features of patients with the condition. This was mainly due to the limited availability of engineered special low protein foods (SLPF) and PKU protein substitutes to use. Nowadays, SLPF foods and micronutrient-enriched PKU protein substitutes have become widely available and are free on prescription in most countries. These SLPF are high in carbohydrates and often in fat content, have a higher glycaemic index and provide more energy per weight compared with the protein-containing equivalent normal foods. Advancement in the PKU management, including dietary practices, led to nutritional problems that had never been reported before, but have become more frequent in the recent years. Overweight and obesity, rather than undernutrition, have become increasingly reported in patients with PKU, with some studies suggesting higher prevalence in females than males. Data on body composition in patients with PKU are inconsistent with some studies showing that patients with PKU have higher FM and lower FFM compared to healthy controls. This suggests that for a given body weight and height, patients with PKU might be fatter and look bigger. However, there is very little research looking at the determinants of nutrient status, body composition and obesity in patients with PKU. Hence, among the aims of this thesis was to investigate the impact of a PKU SLPF-based meal on appetite ratings, gut appetite hormones, thermic effect of feeding (TEF) and fat oxidation (Chapter 2). Twenty-three healthy adults (mean ± SD age: 24.3 ± 5.1 years; BMI: 22.4 ± 2.5 kg/m2) participated in a randomised crossover study. Each participant conducted two (PKU and Control) experimental trials which involved consumption of a PKU SLPF-based meal and protein substitute drink or an isocaloric and weight matched ordinary meal and protein-enriched milk drink. Appetite, metabolic rate, fat oxidation measurements and blood collections were conducted for the duration of 300 minutes. On completion of the measurements, an ad libitum buffet dinner was served. Responses of appetite ratings, plasma concentrations of GLP-1 and PYY (P > 0.05, trial effect, two-way ANOVA) and energy intake during ad libitum buffet dinner (P > 0.05, paired t-test) were not significantly different between the two trials. The TEF (PKU, 10.2 ±1.5%; Control, 13.2 ± 1.0%) and the total amount of fat oxidised (PKU, 18.90 ± 1.10 g; Control, 22.10 ± 1.10 g) were significantly (P < 0.05, paired t-tests) lower in the PKU than in the Control trial. The differences in TEF and fat oxidation were significant (P < 0.05, paired t-tests) for the post-meal period. Therefore, from this first study we concluded that consumption of a meal composed of SLPF has no detrimental impact on appetite and appetite hormones but produces a lower TEF and postprandial fat oxidation than an ordinary meal. We hypothesised that these metabolic alterations may contribute to the increased prevalence of obesity reported in patients with PKU on contemporary dietary management. In the second experimental chapter, we tested the hypothesis generated from the study above and measured TEF, fasting and postprandial fat and CHO oxidation in 13 patients with PKU and 10 healthy controls of similar age and BMI. Participants in the PKU group were provided an SLPF-based meal while those in the Control group were provided an isocaloric normal meal. It was found that TEF, and postprandial fat and CHO oxidation were not signifcantly different between the PKU and the Control groups. In addition, this study compared body composition characteristics (measured by Deuterium Oxide dilution technique) between PKU patients and healthy controls and revealed that differences in body composition are not significant between the two groups despite a tendency of PKU patients having higher percentage of body fatness (P=0.08). However, data generated from this study should be interpreted with caution and requires confirmation from studies with larger sample size. Micronutrient imbalance has been noted in patients with PKU despite their high provision through the PKU protein substitutes. Recent studies showed high blood levels of vitamin B12 and folate, but simultaneously deficient plasma levels of selenium and zinc in PKU patients prescribed with micronutrient-enriched PKU protein substitutes. Factors associated with micronutrient imbalance have rarely been studied in the literature. Therefore, the last chapter of this thesis aimed to evaluate the micronutrient status of children with PKU and explore factors associated with micronutrient imbalances and deficiencies. This was analysis of a large clinical dataset with serial measurements obtained from PKU children (≤16 years) attending the metabolic medicine clinic at the Glasgow Royal Hospital for Sick Children between 1990 and 2013. The study included 81 patients who provided a total of 512 blood samples for their routine annual micronutrient screening. Data on blood micronutrient measurements was available for vitamins A, B12, D, E, serum folate, and erythrocyte folate and the trace elements copper, selenium, zinc and serum ferritin as a biomarker of iron stores. Status of vitamin B12, E, and serum and erythrocyte folate measurements were above the normal range (NR) in 27%, 54%, 46% and 35% of the blood samples, respectively. However, 44% of selenium and 14% of zinc measurements were below the NR. Moreover, when we compared results with those from the UK National Dietary and Nutritional Survey, selenium and zinc deficiencies were specific to PKU condition and not a reflection of the epidemiology in the general UK population. In our PKU sample, poor metabolic control, PKU severity, and low adherence to PKU protein substitutes predicted low selenium status; while deficient zinc status was solely predicted by low adherence to PKU protein substitutes. Yet, these predictors, collectively, explained a small (5.8 – 8.8 %) variation in the status of selenium and zinc in this group of patients. Selenium and zinc deficiencies are common in PKU patients despite high levels of other nutrients including vitamin B12, E and folate. The findings of this study suggest that selenium and zinc deficiencies reported in patients with PKU may be attributed to other factors which we were unable to measure in this retrospective study, such as low bioavailability of these nutrients from the artificial PKU protein substitutes.

Background & Aim: Osteoarthritis (OA) sufferers frequently turn to complementary and alternative medicine (CAM), of which the most common are acupuncture and homeopathy, to improve manageability of their condition. However, there is little extant evidence of effectiveness for these treatments for OA, particularly for homeopathy. One criticism of homeopathic studies is that treatment protocols do not reflect true homeopathy. The nature of true homeopathy is not documented in extant literature. In the current study a mixed methods approach was used to investigate the use of homeopathy for osteoarthritis using a survey, conducted with a parallel acupuncture survey for comparison, follow up interviews with homeopaths and a patient-centred study in a homeopathic department offering treatment on the NHS, in order to inform future studies. Method: The current study involved three phases; (1) A descriptive survey conducted on n=362 medical and non-medical homeopaths and acupuncturists, was used to , investigate practice of the therapies (2) Follow up interview of n=28 of the homeopathic practitioners. (3) A patient-centred study of n=11 patients with OA receiving homeopathy in the primary care setting. Results: (1) Most commonly encountered conditions were chronic diseases. Medical and non-medical acupuncturists practised very different forms of acupuncture particularly in terms of diagnostic techniques used and theoretical underpinning. Homeopathic practitioners used individualised treatments, abiding by classical homeopathy. Differences between medical and non-medical homeopaths included time spent in the consultation (p= 0.01), strength of confidence in homeopathy for asthma (p=0.01), musculo-skeletal (p=0.046) and acute conditions (p=0.01)., and confidence in conventional medicine (p=0.01). There was a belief amongst acupuncturists and homeopaths that the treatments may work on electrodynamic fields in the body. (2) A similar approach was taken by participants during a detailed initial consultation. However, irrespective of medical status, varied approaches were used to identify the remedy, potency, and remedy f6mi, and the source of remedy also varied. Main themes regarding the modus operandi of homeopathy included stimulation of self healing mechanisms and identifying in detail events at the point where the initial health imbalance occurred. Identification of this point together with the patient was considered a potential trigger for the healing process to begin, adding a particular importance to the role of the consultation. (3) OA patients in the primary care setting identified pain or stiffness as the most common primary complaint., with an emotional factor such as anxiety and limitations caused by their condition as a secondary complaint. A desire to reduce their medication or to improve the manageability of their condition was a common theme for interest in receiving homeopathy, with access to NHS homeopathic treatment and perceived safety of receiving treatment from medical doctors being important factors. Following 6 months of' homeopathic treatment, most participants reported an improvement in the manageability of their condition. This, however was not supported by results from VAS pain, VAS stiffness, MYCAW scores or SF36 subscore, or salivary concentration of substance P results which were not found to be significant. Few correlations were found between outcome measures. Substance P level was strongly correlated with the functional limitations sub-score of the SF36 (p=0.01), indicating a potential role for this biochemical measure in future studies. Conclusion: Findings from the current study can inform future studies on how to enhance the evidence base for homeopathic and acupuncture treatment, and inform the integration debate. Future advances in the understanding of subtle processes in the body, the placebo response, and the nature of cure may add to our understanding of' CAM treatments. However, it is likely that in order to advance the evidence base on the effectiveness of homeopathy for OA, more effective tools that are sensitive to changes in biopsychosocial dimensions of health will be necessary. Future research on combination therapies is also warranted.

The aim of the present thesis was to examine imitation of biological motion in adults with autism spectrum disorders. Using a novel behavioural protocol, adults with autism and matched neurotypical control adults imitated models that displayed distinctly different, but biological believable kinematics. In Chapter Two it was observed that adults with autism exhibited low-fidelity imitation of atypical biological motion. In Chapter Three it was observed that when selective-attention instructions were provided, although eye movements recorded during action- observation was similar to controls, imitation of atypical biological motion was still impaired. In Chapter Four across three experiments it was shown that adults with autism exhibit reasonably high-fidelity imitation of atypical biological motion. This was achieved by presenting the to-be-imitated biological models in a fixed presentation structure which is known to facilitate greater integration and consolidation of sensorimotor information. This suggestion was supported by a further study where firstly participants were required to complete a secondary motor task during the inter-trial delay, and when the presentation structure was randomised (similar to Chapters Two and Three) resulting in low-fidelity imitation of atypical biological motion. These findings across the present thesis will be discussed in light of a critical evaluation with respect to current literature on imitation in autism, as well as implications for theoretical accounts of impaired imitation in autism and related sensorimotor control processes. Future considerations and translational research will be discussed, with the intention of offering prospective social rehabilitation protocols in autism.

The goal of this thesis is to identify the underlying impairments in aphasic disorders of auditory comprehension and repetition. The findings are interpreted within a cognitive neuropsychological framework. Models of normal language processing are discussed in the light of this evidence. Information processing models of the lexicon attempt to specify the stages of processing necessary for auditory comprehension, as well as different routes by which words can be repeated. Twenty fluent aphasic patients were used in the study. It was found that the patients did show qualitative differences in auditory word comprehension. Five levels of impairment were identified: word-sound deafness, word-for deafness, word-meaning deafness, a central semantic disorder and a disorder specific to abstract words. It was concluded that abstract words are more sensitive to impairment than concrete words. Word imageability was investigated in more detail in a number of experiments with a word meaning deaf patient (DRB). It was shown that his impairment is one of access from the input lexicon to the semantic system. The impairment results in under-specification in the semantic system, and an extremely robust effect of imageability in DRB's ability to comprehend and repeat auditorily presented words. This effect is not item-specific. Intriguingly, the results also suggest that DRB has an anomia for words of low imageability. In a subsequent section, the patients' abilities in repetition are investigated. Two routes for repetition are identified, a sub-lexical and a lexical/semantic route. Phonologically related errors arising in the former route tend to be non-words, occur particularly on longer words, and the errors tend to be in the final position of the string. Phonological errors arising in the lexical/semantic route are real words, tend to be higher in frequency than the stimulus items, and occur particularly on shorter words. The relationship between repetition and auditory short term memory is considered by further experiments with DRB. It is argued that sub-lexical repetition utilises the auditory short term memory system. DRB's sub-lexical repetition and his immediate serial recall are enhanced by lip read information. A model of repetition and auditory short-term memory is presented. It is argued that the system requires different input and output phonological codes, suggesting separate input and output lexicons. With the specification of how lexical information supports immediate serial recall, it is argued that there is no requirement for a direct, lexical, non-semantic route in repetition.

The ligaments of the trapeziometacarpal joint (TMC) are complex and highly varied. Several studies have reported different patterns of ligament arrangement. Which ligaments are responsible for governing the stability of the TMC is still a source of controversy; the very naming of some of the ligaments is also in dispute. The overall aim of the experiments in this thesis is to explore the stabilization of the TMC ligaments during a specific positions (the neutral and full abduction positions), the mechanics of the attachment, the relaxing and stretching of the TMC ligaments, and the responsibilities of the TMC ligaments to prevent the TMC joint subluxations such as dorsal subluxation, palmar subluxation, and lateral subluxation. An additional aim is to describe the orientation of the TMC ligaments (origin, insertion) and the ligament fibres’ directions. The study used development devices to render the TMC ligaments into 2D reconstruction and 3D modelling in the 3D virtual environment such as Rhinoceros V5, 3D Landmark software, and 3D Amira software. Length, width, area, volume, thickness, and cross-sectional measurements were assessed in the neutral and full abduction positions. The ligament stretcher was designed to stretch the TMC ligaments after the ligaments were cut away from the joint. Also used in the thesis is a new technique to develop staining procedures by combining two different stains with accurate timing and re-timing the procedures of the Miller’s Elastin Staining protocol. Also, the entheses investigations have been applied on the attachments of the TMC ligaments with trapezuim and first metacarpal bones (proximal and distal). Moreover, the technique of the high resolution episcopic microscopy (HREM) was used to identify the relation of the TMC ligaments fibres to the flexor retinaculum, especially at dorso-ulnar trapeziometacarpal ligament (DUTML). The layers of the palmar trapeziometacarpal ligament (PTML) were also investigated to identify the nature of this ligament. The osteological descriptions were noted for the first metacarpal and trapezium bones, the geometrical measurement experiments on the articular surface of both bones allowed for a description of the effects of the degenerative disease, especially osteioarthritis disease (OA), and comparisons between both genders, the right and left specimens, embalmed and fresh cadavers were investigated to achieve the most accurate and precise results. The index procedures against the third metacarpal assisted in describing the relation between the actual reading and index reading. Seven ligaments were shown in the 3D virtual environment: radial trapeziometacarpal ligament (RTML), superficial palmar trapeziometacarpal ligament (sPTML), deep palmar trapeziometacarpal ligament (dPTML), palmo-ulnar trapeziometacarpal ligament (PUTML), dorso-ulnar trapeziometacarpal ligament (DUTML), palmar intermetacarpal ligament (PIML), and dorsal intermetacarpal ligament (DIML). Also, the results revealed that the PIML and DIML were the main stabilizers through the experiments, and the DUTML and PUTML served as associated ligaments to prevent TMC joint dislocation. The RTML prevented radial subluxation, while the superficial and deep layers of the PTML acted as a pivot for the movement of the TMC joint and assisted in preventing a palmar subluxation. In addition, there were no significant differences (p > 0.05) between embalmed and fresh cadavers, but there were significant differences (p < 0.05) between male and female cadavers as well as between the right and left hands, especially in the measurement investigations. Moreover, the TMC ligament attachments were found to be of the fibrocartilagenous type; this was found at both attachments, proximal and distal. The combination beginning with Miller Elastin stain (ME) was better than that starting with Modified Masson Trichrome stain (MME) and the colours were nearer to those of the MMT results; however, the MMT alone was clearest. Also, a re-timing of the ME stain revealed that the experiment involving 2.5 hours of Miller’s Elastin and 15 seconds of Van Gieson Solution was the best of all experiments. The HREM technique revealed no connection between the collagen fibres of both the DUTML and the flexor retinaculum. The single coordination points of each of the first metacarpal (1st MC) and trapezium (TM) bones revealed varieties of prominences and declines in the bones’ surfaces, especially the articular surface. New names of the TMC ligaments as following: Old Name New Name Ulnar collateral ligament (UCL). Radial trapeziometacarpal ligament (RTML). Superficial anterior oblique ligament (sAOL). Superficial palmar trapeziometacarpal ligament (sPTML). Deep anterior oblique ligament (dAOL). Deep palmar trapeziometacarpal ligament (dPTML). Posterior oblique ligament (POL). Palmo-ulnar trapeziometacarpal ligament (PUTML). Dorso-radial ligament (DRL). Dorso-ulnar trapeziometacarpal ligament (DUTML). New osteological definitions were noted, such as the distal border of the 1st MC facet, the distal and proximal ridge of the palmar surface of the1st MC, and eminences of the trapezial ridge of TM. Overall, the results of my studies suggested that the importance of the PIML, DIML, and RTML should be considered when planning surgeries involving ligament reconstruction of the TMC joint.

Short chain fatty acids (SCFA), including propionate, are produced by the bacterial fermentation of carbohydrates in the colon. Propionate has many potential roles in health, including inhibiting cholesterol synthesis, de novo lipogenesis and increasing satiety. The profile of SCFA produced is determined by both the substrate available and the bacteria present and may be influenced by environmental conditions within the lumen of the colon. Whilst it may be beneficial to increase colonic propionate production, dietary strategies to achieve this are unproven. Adding propionate to food leads to poorer organoleptic properties, and oral propionate is absorbed in the small intestine. The optimum way to selectively increase colonic propionate would be to select fermentable carbohydrates that selectively promote propionate production. To date, few studies have undertaken a systematic assessment of the factors leading to increased colonic propionate production making the selection of propiogenic carbohydrates challenging. The aim of this thesis was to identify the best carbohydrates for selectively increasing propionate production, and to explore the factors which control propionate production. This work started with a systematic review of the literature for evidence of candidate carbohydrates, which led to a screen of ‘propiogenic’ substrates using in vitro batch fermentations and mechanistic analysis of the impact of pH, bond linkage and orientation using a range of sugars, polysaccharides and fibre sources. A new unit for SCFA production was developed to allow comparison of results from in vitro studies encompassing a range different methodologies found in the literature. The systematic review found that rhamnose yielded the highest rate and proportion of propionate production whereas, for polysaccharides, β-glucan ranked highest for rate and guar gum ranked highest for molar production, but this was not replicated across all studies. Thus, no single NDC was established as highly propiogenic. Some substrates appeared more propiogenic than others and when these were screened in vitro. Laminarin, and other β-glucans ranked highest for propionate production. Legume fibre and mycoprotein fibre were also propiogenic. A full complement of glucose disaccharides were tested to examine the role glycosidic bond orientation and position on propionate production. Of the glucose disaccharides tested, β(1-4) bonding was associated with increased proportion of propionate and α(1-1) and β(1-4) increased the rate and proportion of butyrate production. In conclusion, it appears that for fibre to affect satiety, high intakes of fibre are needed, and which a major mechanism is thought to occur via propionate. Within this thesis it was identified that rather than selecting specific fibres, increasing overall intakes of highly fermentable carbohydrates is as effective at increasing propionate production. Selecting carbohydrates with beta-bonding, particularly laminarin and other β(1-4) fermentable carbohydrates leads to marginal increases in propionate production. Compared with targeted delivery of propionate to the colon, fermentable carbohydrates examined in this thesis have lesser and variable effects on propionate production. A more complete understanding of the impact of bond configurations in polysaccharides, rather than disaccharides, may help selection or design of dietary carbohydrates which selectively promote colonic propionate production substrates for inclusion in functional foods. Overall this study has concluded that few substrates are selectively propiogenic and the evidence suggests that similar changes in propionate production may be achieved by modest changes in dietary fibre intake.