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George T. Macfarlane, Ph.D
Professor of Bacteriology,
University of Dundee, Microbiology and Gut Biology Group,
Ninewells Hospital Medical School, Dundee DD1 9SY, UK

Background:
The speaker is a microbiologist who has worked on various aspects of the human intestinal microbiota for
30 years. His initial work with the Medical Research Council in the 1980s involved studies on resistant starchand polysaccharide breakdown by gut bacteria, together with investigations on in vitro modelling, proteolysis,and hydrogen metabolism, particularly in relation to dissimilatory sulphate reduction. Subsequently, investigations were undertaken on prebiotics, ageing, and bacterial bioﬁlms in the gastrointestinal tract. After moving
to the University of Dundee in 1999, research focused on mucosal bacterial communities in IBD, and theirstructural modiﬁcation with synbiotics and antibiotics. Current projects involve modelling bacterial bioﬁlms
and cellular interactions in Barrett’s oesophagus, as well as studies on Clostridium difﬁcile
Research interests:
Human colonic bacteria: ecology, physiology and pathogenicity
Ageing and the intestinal microbiotaEnvironmental regulation of virulence determinants in pathogenic microorganisms
Growth and metabolic activities of intestinal bacteria on mucosal surfaces and bioﬁlms
Bacterial involvement in inﬂammatory bowel disease and cancer
Probiotics and prebiotics
Positions:
1984‑1994:
1994‑1999:
1999‑2001:
2001‑2013:

Medical Research Council Career Research Scientist, Dunn Clinical Nutrition Centre (DCNC),
Cambridge
MRC Senior Research Scientist (DCNC)
Senior lecturer, The University of Dundee
Appointed to a Personal Chair in Bacteriology, The University of Dundee

Other work
1987‑1992: Editorial Board Member, Journal of Applied Bacteriology
1992‑1996: Senior Editor, Journal of Applied Bacteriology
1999‑2014: Associate Editor, Journal of Applied Microbiology
1999‑2014: Associate Editor, Letters in Applied Microbiology
2004‑2008: Editor, Bioﬁlms
2002‑2011: Editorial Board Member, Applied and Environmental Microbiology
2011‑2015: Editor, Applied and Environmental Microbiology
Since 2001:

Member of 19 national and international research assessment and grant awarding committees
Invited speaker at 50 national and international scientiﬁc conferences
Author or co-author of 76 publications

Professional memberships
Society for General Microbiology, Society for Applied Microbiology, American Society for Microbiology, British
Society for Gastroenterology, Pathological Society, Fellow of the Society of Biology, Fellow of the Royal
Society of Medicine

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腸内細菌学雑誌

27 巻 2 号

2013

Ecology of intestinal microorganisms in health and disease
George T. Macfarlane
University of Dundee, Microbiology and Gut Biology Group,
Ninewells Hospital Medical School
This presentation will focus on the role of intestinal bacteria in colon cancer, and inﬂammatory
bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn’s disease (CD), as well as conditionsin the upper gut, such as bacterial overgrowth in patients receiving enteral nutrition (EN), as wellas Barrett’s oesophagus and oesophageal adenocarcinoma.
Intestinal microorganisms play a major role in human physiology. Until relatively recently, mostwork has focused on luminal contents in the large bowel, however, there is increasing evidence
that mucosal surfaces are heavily colonised throughout the digestive tract, including the upper gut
in various disease states, although the species composition and microbial load is normally much
lower in this region of the digestive tract. Despite this, dysbiosis associated with upper gut colonisation can cause major health problems.
Barrett’s oesophagus (BO) is a complication of chronic gastro-oesophageal reﬂux disease, in which
individuals have a greatly increased risk of adenocarcinoma. To investigate whether microbial bioﬁlm communities might play a role in the disease process, bacterial populations in oesophageal
aspirates, and oesophageal mucosae of BO patients were studied, together with healthy controls.
Confocal microscopy was also used to determine the spatial localisation of these organisms onmucosal surfaces. Overall, 46 bacterial species belonging to 16 genera were detected by culturing, with 10 species being common to both subject groups. Both aspirate and biopsy samples from
BO patients contained complex microbial communities. Interestingly, high levels of campylobacters(C. concisus, C. rectus), were found in BO patients, but not in non-diseased controls. Microscopy
showed that mucosal bacteria were often present in microcolonies. The presence of pathogenic
campylobacters in people with BO may suggest a link either in the initiation, maintenance or
exacerbation of the disease processes leading to adenocarcinoma formation. Interactions of C. concisus and Barrett’s cell lines in vitro show that these bacteria interfere with signalling factors (e.g.
COX2, CDX1, P53) at a number of points in the cell cycle, while these eﬀects are not seen withthe commensal bacterium Streptococcus salivarius.
In healthy people, the small bowel is normally sparsely populated by microorganisms. This isdue, in part, to the rapid ﬂow of digestive materials through the gut, which prevents the establishment of permanent communities. However, during enteral feeding via percutaneous endoscopic gastrostomy tubes, innate defence mechanisms in the upper gut are bypassed, resulting in microbialovergrowth. The eﬀects of EN on mucosal colonisation, and the gut-associated immune system, are
not well understood, but studies on surface-associated microbial populations in the gastric and duodenal mucosae of patients receiving EN showed that there were signiﬁcantly higher levels of bacterial DNA in mucosal biopsies from both sites in these individuals, compared to control subjects.
The main organisms found were staphylococci and enterobacteria. Allied to this, the expression of
pro-inﬂammatory cytokines such as IL1-α , IL6 and TNF-α , was signiﬁcantly higher in gastric and第 17 回腸内細菌学会

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while Faecalibacterium prausnitzii was more signiﬁcant in the proximal and descending colon.
Mucosal-associated bacterial diversity was host-dependent in that considerable inter-individual variation was observed. However, studies in cancer patients showed diﬀerential colonisation of tumoursites and healthy tissues, with bacteroides and enterobacteria predominating on the tumours, andbiﬁdobacteria occurring to a greater extent in non-diseased tissues.
The aetiologies of inflammatory bowel diseases such as UC and CD are unclear, but it isbelieved that intestinal bacteria are involved in some way in these dysbiotic processes. Both viablecounting and molecular analyses of rectal biopsies have shown that marked diﬀerences exist insome bacterial communities, particularly biﬁdobacteria, which are present in much lower numbers
on mucosal surfaces. Whether this is simply due to local environmental changes caused by thedisease, or is linked to disease initiation is unclear. However, feeding studies in both UC and CD
patients with a Biﬁdobacterium longum/inulin/fructo-oligosaccharide synbiotic have been shown toincrease biﬁdobacterial numbers and diversity in both forms of IBD, with concomitant relief of tissue inﬂammation and disease symptoms.

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small intestinal mucosae from patients fed normal diets, in comparison with those receiving EN.
These studies demonstrated that EN resulted in signiﬁcant bacterial overgrowth in the upper gut,and paradoxically, reduced pro-inﬂammatory cytokine responses, which may facilitate spread of theorganisms through the body.
Investigations on the large gut have shown that the bowel wall is heavily colonised by diverseand highly complex bacterial communities. Healthy mucosal tissue from diﬀerent regions of thelarge bowel were obtained from 26 patients undergoing emergency resection of the colon, andused to study mucosal bioﬁlm communities in the distal gut. Quantitative bacteriological measurements were done by qPCR. Mucosal bacteria were also visualised using confocal microscopy.
Mucosal cell population densities were highest in the terminal ileum, while there was no signiﬁcant diﬀerence in overall bacterial numbers in diﬀerent parts of the colon. Biﬁdobacteria weremore important in the large bowel than in the terminal ileum, while lactobacilli were more prominent in the distal colon. Eubacterium rectale occurred in higher numbers in the ascending colon