G T Macfarlane

University of Dundee, Dundee, Scotland, United Kingdom

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Publications (106)367.42 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The colonisation and establishment of the intestinal microbiota starts immediately at birth and is essential for the development of the intestine and the immune system. This microbial community gradually increases in number and diversity until the age of two or three years when it becomes a stable ecosystem resembling that of adults. This period constitutes a unique window of opportunity to modulate it through probiotic action, with a potential impact in later health. In the present work we have investigated how putative bifidobacterial probiotics modify the metabolic profiles and immune-modulatory properties of faecal microbiotas. An in vitro pH-controlled single-stage continuous-culture system (CCS) inoculated with infant faeces was employed to characterise the effects of two Bifidobacterium species on the intestinal microbiotas in three children, together with the effects of these modified microbiotas on cytokine production by HT-29 cells. Intestinal bacterial communities, production of short-chain fatty acids and lactate were determined by quantitative PCR and gas chromatography, respectively. Cytokines production by HT-29 cells was measured by ELISA. The combination of CCS with infant faeces and human intestinal cells provided a suitable model to evaluate the specific modulation of the intestinal microbiota and immune system by probiotics. In the CCS, infant faecal microbiotas were influenced by the addition of bifidobacteria, resulting in changes in their ability to induce the production of immune mediators by HT-29 cells. The different metabolic and immunological responses induced by the bifidobacterial species tested indicate the need to assess potential probiotics in model systems including complex intestinal microbiotas. Potential probiotic bifidobacteria can modulate the infant microbiota and its ability to induce the production of mediators of the immune response by intestinal cells.
    Beneficial Microbes 02/2015; 1(-1):1-10. DOI:10.3920/BM2014.0111 · 1.50 Impact Factor
  • S Macfarlane · S Cleary · B Bahrami · N Reynolds · G T Macfarlane
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    ABSTRACT: Ageing can result in major changes in the composition and metabolic activities of bacterial populations in the large gut and an impaired immune system. To investigate the effects of synbiotic consumption on the colonic microbiota, immune function and health status in older people. A randomised, double-blind placebo-controlled, 4-week crossover study was carried out, involving 43 older volunteers, using a synbiotic comprising the probiotic Bifidobacterium longum and an inulin-based prebiotic Synergy 1 (SudZucker, Mannheim, Germany). Faecal and blood samples were collected, and clinical status scored at the start, and at 2- and 4-week intervals, with a 4-week washout between each feeding period. Faecal bacteria were determined by fluorescent in situ hybridisation. Short-chain fatty acid concentrations, cytokine production, bowel habit and a range of clinical parameters were measured. The synbiotic increased bifidobacterial numbers by 1.4 log units (P < 0.0001) and also increased members of the phyla Actinobacteria and Firmicutes (P = 0.0004, P < 0.0001). Proteobacteria were reduced by 1.0 log units (P < 0.0001). Synbiotic feeding was associated with increased butyrate production (P = 0.0399). The pro-inflammatory response was modified by the synbiotic, with significantly reduced pro-inflammatory cytokine TNF-α in peripheral blood after 2 and 4 weeks of synbiotic consumption (P = 0.02, P = 0.0406). The synbiotic had no effect on bowel habit or any clinical parameters. Short-term synbiotic use can be effective in improving the composition and metabolic activities of colonic bacterial communities and immune parameters in older people. This study was registered at clinicaltrials.gov as NCT01226212.
    Alimentary Pharmacology & Therapeutics 08/2013; 38(7). DOI:10.1111/apt.12453 · 4.55 Impact Factor
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    ABSTRACT: Barrett's oesophagus (BO) and gastro-oesophageal reflux disease (GERD) are precursors of oesophageal adenocarcinoma (OAC). There is an oesophageal biofilm, which changes in disease, but its role in aetiopathogenesis remains unclear. To define the oesophageal microbiota of patients with GERD, BO and OAC compared with controls and to investigate mucosal responses related to the microbiota. Cultural analysis identified the dominant bacterial species from a subset of each disease group. Based on this, molecular techniques were used to define the cohort. Host responses were analysed in tissues and co-culture experiments. A total of 111 species belonging to 26 genera were isolated. There was a significant decrease in bacterial counts in the GERD and BO groups for all genera except Campylobacter, which colonised GERD and Barrett's patients in increasing numbers. Campylobacter concisus was the dominant species. This relationship was not seen in the cancer group. Significant increases in IL-18 were seen in GERD and BO colonised by Campylobacter. This study defines differences in the oesophageal biofilm in disease states, revealing the emergence of C. concisus as the dominant new colonist in the refluxed oesophagus. We also associate the presence of these bacteria with increased expression of cytokines related to carcinogenesis.
    Alimentary Pharmacology & Therapeutics 04/2013; 37(11). DOI:10.1111/apt.12317 · 4.55 Impact Factor
  • R Hansen · G Mahdi · K McIntyre · G T Macfarlane · S Macfarlane · D C Wilson
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    ABSTRACT: IntroductionAn altered colonic microbiota contributes to inflammatory bowel disease (IBD) pathogenesis. Adult studies suggest modification of the microbiota by synbiotics (probiotics+prebiotics) can improve ulcerative colitis (UC)1 and Crohn's disease (CD)2.AimTo assess the feasibility of using a synbiotic in children with IBD.Methods Patients with IBD aged 6 to 16 years were approached. Children were excluded if they used any prebiotic/probiotic agent in the preceding 14 days, were using antibiotics or had a severe IBD exacerbation. Patients were withdrawn if they started antibiotics or another prebiotic/probiotic or they wished to discontinue. Participation involved taking the probiotic (Bifidobacterium longum in a capsule) and prebiotic (3.5 g Synergy 1 inulin oligofructose) twice daily for 12 weeks. A pre-study questionnaire and physician's global assessment (PGA) were completed. Questionnaires were provided for return at 1, 4, 8 and 12 weeks. Trial completion involved finishing the synbiotic course and returning all questionnaires.Results23 children were recruited. 11 (48%) were male. Median age was 13.4 years (7.8–16.6 years). 11 had CD, 6 UC and 4 IBD-unspecified. Initial PGA was ‘inactive’ in 19, ‘mild’ in 3, ‘moderate’ in 1 and ‘severe’ in 1. Only 3 of the first 17 patients completed the study. Feedback indicated the prebiotic was poorly tolerated, therefore the last six participants undertook a tapered probiotic course: none in week 1, once daily in week 2, then twice daily from week 3. Only two of six completed the modified study. Completion overall was 5/23 (22%). Reasons for withdrawal were: six diarrhoea/IBD flare, six stopped returning questionnaires, four required antibiotics, one advised by GP because of rash, one unwell on prebiotic but completed probiotic and one parent stopped after noticing ‘no difference.Conclusion Although synbiotics have shown promise in adult IBD this feasibility study in fairly well paediatric IBD patients has shown poor tolerability. We suspect the drop-out rate was due to the prebiotic agent, but further studies are necessary to assess the tolerance of different prebiotics/probiotics in paediatric IBD before larger efficacy trials.
    Archives of Disease in Childhood 04/2011; 96(1). DOI:10.1136/adc.2011.212563.34 · 2.91 Impact Factor
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    ABSTRACT: Crohn's disease is an inflammatory illness in which the immune response against gut microorganisms is believed to drive an abnormal immune response. Consequently, modification of mucosal bacterial communities, and the immune effects they elicit, might be used to modify the disease state. To investigate the effects of synbiotic consumption on disease processes in patients with Crohn's disease. A randomized, double-blind placebo-controlled trial was conducted involving 35 patients with active Crohn's disease, using a synbiotic comprising Bifidobacterium longum and Synergy 1. Clinical status was scored and rectal biopsies were collected at the start, and at 3- and 6-month intervals. Transcription levels of immune markers and mucosal bacterial 16S rRNA gene copy numbers were quantified using real-time PCR. Significant improvements in clinical outcomes occurred with synbiotic consumption, with reductions in both Crohn's disease activity indices (P = 0.020) and histological scores (P = 0.018). The synbiotic had little effect on mucosal IL-18, INF-gamma and IL-1beta; however, significant reductions occurred in TNF-alpha expression in synbiotic patients at 3 months (P = 0.041), although not at 6 months. Mucosal bifidobacteria proliferated in synbiotic patients. Synbiotic consumption was effective in improving clinical symptoms in patients with active Crohn's disease.
    Alimentary Pharmacology & Therapeutics 10/2010; 32(7):872-83. DOI:10.1111/j.1365-2036.2010.04417.x · 4.55 Impact Factor
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    B Bahrami · S Macfarlane · G T Macfarlane
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    ABSTRACT: To investigate the effects of human gut micro-organisms on cytokine production by human intestinal cell lines. Quantitative real-time PCR assays were developed to measure the production of pro-inflammatory (IL-1α, IL-6, IL-18 and TNFα) and anti-inflammatory (TGF-β1, TGF-β2, TGF-β3, IL-4 and IL-10) cytokines in HT-29 and Caco-2 cell lines. They were co-cultured with a range of mucosal bacteria isolated from ulcerative colitis patients, together with lactobacilli and bifidobacteria obtained from healthy people. HT-29 cells were also co-cultured with Campylobacter jejuni, enterotoxigenic Escherichia coli (ETEC), enteropathogenic E. coli and Salmonella typhimurium. The majority of commensal bacteria tested suppressed the expression of anti-inflammatory cytokine mRNA, increased IL-18, reduced IL-1α, and with the exception of nonpathogenic E. coli, reduced TNF-α. All overtly pathogenic species increased both pro-inflammatory and anti-inflammatory cytokine mRNA. Conclusion:  Commensal and pathogenic species induced fundamentally different cytokine responses in human intestinal epithelial cell lines. Interactions between commensal bacteria tested in this study and the innate immune system were shown to be anti-inflammatory in nature, in contrast to the pathogenic organisms investigated. These data contribute towards our understanding of how potential probiotic species can be used to suppress the pro-inflammatory response in inflammatory bowel disease.
    Journal of Applied Microbiology 10/2010; 110(1):353-63. DOI:10.1111/j.1365-2672.2010.04889.x · 2.39 Impact Factor
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    G T Macfarlane · K L Blackett · T Nakayama · H Steed · S Macfarlane
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    ABSTRACT: Crohn's disease and ulcerative colitis are the two principal forms of inflammatory bowel disease (IBD). The root causes of these chronic and acute immunological disorders are unclear, but intestinal microorganisms are known to play a key role in the initiation and maintenance of disease. However, at present, there is no clear evidence for a single transmissible agent being involved in IBD aetiology. Although marked alterations occur in faecal and mucosal bacterial communities in IBD, it is unclear whether they are responsible for causing disease, or are due to changes in the gut environment that result from inflammatory reactions and extensive tissue destruction. Despite the involvement of microorganisms in inflammatory processes, antibiotic therapy has generally been unsuccessful in IBD. However, recent studies involving the use of probiotics, prebiotics and synbiotics suggest that there is potential for controlling these diseases through manipulation of the composition of the gut microbiota, and direct interactions with the gut immune system.
    Current pharmaceutical design 02/2009; 15(13):1528-36. DOI:10.5223/pghn.2013.16.1.17 · 3.29 Impact Factor
  • H Steed · K L Blackett · S Macfarlane · M Miller · G T Macfarlane · J F Dillon
    Gut 01/2009; 58:A68-A69. · 13.32 Impact Factor
  • G T Macfarlane · L E Macfarlane
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    ABSTRACT: The gut is sterile at birth, but is rapidly colonised by faecal and vaginal bacteria of maternal origin. Over the succeeding weeks, months and years, a complex microbiota develops that plays a major role in host physiology. While the digestive tract is colonised to varying degrees by micro-organisms throughout its length, due to acid pH and the short retention time of gastric contents, bacterial numbers in the stomach are usually low. The rapid passage of digestive materials through the upper gut does not provide time for significant bacterial growth to occur, but cell numbers increase considerably in the distal ileum. The rate of movement of intestinal contents slows in the colon, which facilitates the development of complex bacterial communities. The large intestine is an intricate ecosystem that contains a complex microbiota composed of several hundred different types of bacteria. The growth and metabolism of microbial communities in the large intestine are determined by many factors, such as diet, environment and host physiological processes, as well as the anatomic structure of the digestive tract, disease, immunity, host genetics, drugs and ageing. Modifications in diet and host immune system activity, as well as physiological changes in the digestive tract affect microbiota composition in older people. The elderly have fewer bifidobacteria and higher numbers of enterobacteria and clostridia than young adults. Increased antibiotic use in older people and simply going into hospital have been shown to change bacterial community structure in the colonic microbiota, although the metabolic significance of this is unclear.
    Digestive Diseases 01/2009; 27 Suppl 1(Suppl 1):90-8. DOI:10.1159/000268127 · 1.83 Impact Factor
  • G. T. Macfarlane · E. Furrie · S. Macfarlane
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    ABSTRACT: The aetiology of ulcerative colitis (UC) is unknown, but there is evidence that bacteria are needed for initiation and maintenance of the disease. A number of organisms have been associated with UC, but evidence for a specific transmissible agent is weak. Despite this, there is a good case for mucosal bacterial involvement, either through pathogens colonizing the epithelial surface, by non-pathogenic commensal species occupying adhesion sites on the mucosa and preventing invasion by harmful bacteria, or by inappropriate host immune responses to members of the normal microflora. Since mucosal bacteria exist in close juxtaposition to host tissues, it might be expected that they interact to a greater extent with the immune and neuroendocrine systems than their luminal counterparts. For this reason, comparative bacteriological analyses were done on rectal biopsies from patients with active colitis, and individuals who had no inflammatory bowel disease. Complex bacterial communities colonized the rectal mucosa in all subjects and great interindividual variabilities in mucosal bacterial populations were observed in both groups. These organisms often occurred in microcolonies, which may have implications for UC, since it would result in higher localized concentrations of bacterial antigens, or toxins, than would be the case if the organisms were diffusely spread across the mucosa.
  • G.R. Gibson · G.T. Macfarlane
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    ABSTRACT: Electron donor-limited chemostat enrichments were used to isolate sulphate-reducing bacteria (SRB) from human faeces. When acetate, lactate, propionate, butyrate or amino acids were used as electron donors, SRB identical to those found using traditional isolational methods (agar shake dilution series) were obtained. However, chemostat enrichments facilitated the isolation of SRB able to metabolize mixtures of alcohols (C1-C5) and mixtures of fatty acids (C2-C6) which had not been detected by the direct isolation techniques.
    Letters in Applied Microbiology 06/2008; 7(5):127 - 133. DOI:10.1111/j.1472-765X.1988.tb01308.x · 1.75 Impact Factor
  • G.T. Macfarlane · G.R. Gibson · J.H. Cummings
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    ABSTRACT: Viable counts of anaerobic bacteria increased distally from the right to left regions of the human colon. A wide variety of cell-bound glycosidases were detected in the bowel and their specific activities were generally greater in the right colon. High levels of enzymes associated with the degradation of endogenously produced glyco-proteins were found throughout the large intestine without significant regional differences.
    Letters in Applied Microbiology 06/2008; 12(1):3 - 7. DOI:10.1111/j.1472-765X.1991.tb00488.x · 1.75 Impact Factor
  • G.T. Macfarlane · C. Allison · G.R. Gibson
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    ABSTRACT: The influence of pH on proteolysis in different fractions of human faeces was studied with a variety of chromogenic substrates. The pH optima of proteases in the washed cell fraction and washed particulate fraction were neutral to alkaline, whereas extra-cellular proteolysis in the cell-free supernatant fraction was relatively insensitive to pH over the range 6·4–8·0. Measurements with p-nitroanilide substrates suggested the presence of more than one elastase-like, trypsin-like and chymotrypsin-like protease in the gut.
    Letters in Applied Microbiology 06/2008; 7(6):161 - 164. DOI:10.1111/j.1472-765X.1988.tb01269.x · 1.75 Impact Factor
  • C. Allison · G.T. Macfarlane
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    ABSTRACT: Clostridium perfringens C1051 isolated from human faeces was studied to determine physiological and nutritional factors that govern protease production in the colon. In batch culture extracellular protease was formed during exponential growth but ceased in the stationary phase. In both glucose- and peptide-limited chemostats protease activities increased with culture dilution rate. Proteolysis was greatest under glucose limitation at low growth rates (D= 0·1/h to D= 0·35/h), but no difference was found in the relative amounts of protease produced when dilution rates were increased to 0·7/h. In batch culture protease formation was optimal at pH 6·0. Ammonium chloride and glucose concentrations over the range 1–10 g/l had no significant effect on protease production, but high concentrations of peptone were stimulatory.
    Letters in Applied Microbiology 03/2008; 9(2):45 - 48. DOI:10.1111/j.1472-765X.1989.tb00287.x · 1.75 Impact Factor
  • J.H. Cummings · G.T. Macfarlane
    Journal of Applied Microbiology 03/2008; 70(6):443 - 459. DOI:10.1111/j.1365-2672.1991.tb02739.x · 2.39 Impact Factor
  • G T Macfarlane · H Steed · S Macfarlane
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    ABSTRACT: Most studies involving prebiotic oligosaccharides have been carried out using inulin and its fructo-oligosaccharide (FOS) derivatives, together with various forms of galacto-oligosaccharides (GOS). Although many intestinal bacteria are able to grow on these carbohydrates, most investigations have demonstrated that the growth of bifidobacteria, and to a lesser degree lactobacilli, is particularly favoured. Because of their safety, stability, organoleptic properties, resistance to digestion in the upper bowel and fermentability in the colon, as well as their abilities to promote the growth of beneficial bacteria in the gut, these prebiotics are being increasingly incorporated into the Western diet. Inulin-derived oligosaccharides and GOS are mildly laxative, but can result in flatulence and osmotic diarrhoea if taken in large amounts. However, their effects on large bowel habit are relatively minor. Although the literature dealing with the health significance of prebiotics is not as extensive as that concerning probiotics, considerable evidence has accrued showing that consumption of GOS and FOS can have significant health benefits, particularly in relation to their putative anti-cancer properties, influence on mineral absorption, lipid metabolism, and anti-inflammatory and other immune effects such as atopic disease. In many instances, prebiotics seem to be more effective when used as part of a synbiotic combination.
    Journal of Applied Microbiology 03/2008; 104(2):305-44. DOI:10.1111/j.1365-2672.2007.03520.x · 2.39 Impact Factor
  • S. Macfarlane · G. T. Macfarlane
    Gut Flora, Nutrition, Immunity and Health, 02/2008: pages 24 - 61; , ISBN: 9780470774595
  • K L Blackett · G T Macfarlane · J F Dillon · S Macfarlane
  • K L Blackett · G T Macfarlane · S Macfarlane · J F Dillon
    Gut 01/2008; 57:A124-A124. · 13.32 Impact Factor
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    S Macfarlane · G T Macfarlane · J H Cummings
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    ABSTRACT: Prebiotics are short-chain carbohydrates that alter the composition, or metabolism, of the gut microbiota in a beneficial manner. It is therefore expected that prebiotics will improve health in a way similar to probiotics, whilst at the same time being cheaper, and carrying less risk and being easier to incorporate into the diet than probiotics. To review published evidence for prebiotic effects on gut function and human health. We searched the Science Citation Index with the terms prebiotic, microbiota, gut bacteria, large intestine, mucosa, bowel habit, constipation, diarrhoea, inflammatory bowel disease, Crohn's disease, ulcerative colitis, pouchitis, calcium and cancer, focussing principally on studies in humans and reports in the English language. Search of the Cochrane Library did not identify any clinical study or meta-analysis on this topic. Three prebiotics, oligofructose, galacto-oligosaccharides and lactulose, clearly alter the balance of the large bowel microbiota by increasing bifidobacteria and Lactobacillus numbers. These carbohydrates are fermented and give rise to short-chain fatty acid and intestinal gas; however, effects on bowel habit are relatively small. Randomized-controlled trials of their effect in a clinical context are few, although animal studies show anti-inflammatory effects in inflammatory bowel disease, while calcium absorption is increased. It is still early days for prebiotics, but they offer the potential to modify the gut microbial balance in such a way as to bring direct health benefits cheaply and safely.
    Alimentary Pharmacology & Therapeutics 10/2006; 24(5):701-14. DOI:10.1111/j.1365-2036.2006.03042.x · 5.48 Impact Factor

Publication Stats

9k Citations
367.42 Total Impact Points

Institutions

  • 2000–2015
    • University of Dundee
      • • Medical Research Institute
      • • Division of Neuroscience
      Dundee, Scotland, United Kingdom
  • 2006–2008
    • Ninewells Hospital
      Dundee, Scotland, United Kingdom
  • 2000–2001
    • London South Bank University
      • Department of Applied Science
      London, ENG, United Kingdom
  • 1997
    • MRC Clinical Sciences Centre
      London Borough of Harrow, England, United Kingdom