ABSTRACT

CONTENTS Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 Composition of Microflora . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Roles of the Microflora . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Metabolic Functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Pathogen Resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Nutrient Availability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 Bacteriocins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 The Gut Microbiota and Interactions with the Immune System . . . . 19

Factors Affecting Composition of the Microflora . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Modulating the Composition of the Microflora . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

Probiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Lactic Acid Bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Bifidobacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 Prebiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 Synbiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 Anti-Adhesive Oligosaccharides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

Host-Probiotic: Specific Interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 Immunity Enhancement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 Interaction with Mucus Layer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Probiotics and the Healthy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Systemic Effects of Probiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

Inflammatory Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 Pouchitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 Ulcerative Colitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 Irritable Bowel Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

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The intestinal mucosa is the main site of interaction with the external environment and therefore has an important role in maintaining good health. Formation of the gut is one of the first outcomes ofmulticellularity.1 It appears on first impression to be quite a simple organ as it is an epithelial tube comprising different cells surrounded by a layer of muscle. However, the human gastrointestinal tract is a highly dynamic ecosystem. The total area of the mucosal surface of the human gastrointestinal tract is 300m2 which makes it the largest surface area in the body that interacts with the external environment.2 The gut houses an enormous microbial community with total estimates in the region of 1014 microorganisms. The distal large intestine is the area of highest colonization with more than 500 different culturable species and up to 100 billion microbial inhabitants.3 The total number of microorganisms present in the gastrointestinal tract varies according to location (see Figure 2.1). For example stomach contents (per gram) could be less than 103 cfu, reaching 104-107 in the small intestine and 1010-1012 per gram in the colonwhere themicrobial numbers are highest.4 The endproduct of digestion (feces) is approximately 60% composed of bacteria.5 The whole microbiome is thought to contain approximately 100 times the number of genes in the human genome.6 There are four main microhabitats in the gastrointestinal

Small intestine Bacterial numbers: c.a. 104-106/ml contents e.g., lactobacilli, Gram-positive cocci

Stomach Bacterial numbers: c.a. 103/ml contents e.g., Helicobacter pylori

Colon Bacterial numbers: c.a. 1012/g contents e.g., bacteroides, bifidobacteria, clostridia, peptostreptococci, fusobacteria, lactobacilli, enterobacteria, enterococci, eubacteria, methanogens, sulphate reducers, etc.