OJEMD  Vol.3 No.7 , November 2013
Gut Microbiota: Physiology and Relationship with Inflammatory Bowel Disease
Abstract: The intestinal microbiota, which evolved over tens of thousands of years along with their human hosts, constitutes a complex and diverse ecosystem whose composition differs from person to person. Accumulating evidence indicates that commensal bacteria exert numerous beneficial physiological effects for humans, including nutrition, protection, metabolism, organ development and immunomodulation. However, mucosal immune responses to intestinal microflora require precise control to allow appropriate defense against potential pathogens but restrict the immune response to beneficial resident bacteria. The task of intestinal homeostasis is accomplished by epithelium and specialized immune system in the gastrointestinal tract. Alternation in the composition of the bacterial community, consisting of increased representation of harmful species or under presence of protective species, or dysbiosis has been linked to various chronic and inflammatory disorders, such as inflammatory bowel disease. An improved understanding of the underlying molecular mechanisms of host-microorganism interactions could bring new insights into onset and pathogenesis of several autoimmune diseases. This review will discuss physiologic properties of commensal microbiota and how dysregulated immune responses to them contribute to chronic mucosal inflammation.
Cite this paper: C. Lin, Y. Lin and H. Chen, "Gut Microbiota: Physiology and Relationship with Inflammatory Bowel Disease," Open Journal of Endocrine and Metabolic Diseases, Vol. 3 No. 7, 2013, pp. 283-292. doi: 10.4236/ojemd.2013.37039.

[1]   C. Kunz, S. Kuntz and S. Rudloff, “Intestinal Flora,” Advances in Experimental Medicine and Biology, Vol. 639, 2009, pp. 67-69.

[2]   R. E. Ley, D. A. Peterson and J. I. Gordon, “Ecological and Evolutionary Forces Shaping Microbial Diversity in the Human Intestine,” Cell, Vol. 124, No. 4, 2006, pp. 837-848.

[3]   T. Sobko, M. Norman, E. Norin, L. E. Gustafsson and J. O. Lundberg, ”Birth-Related Increase in Intracolonic Hydrogen Gas and Nitric Oxide as Indicator of Host-Microbial Interactions,” Allergy, Vol. 60, No. 3, 2005, pp. 396-400.

[4]   V. Buccigrossi, E. Nicastro and A. Guarino, “Functions of Intestinal Microflora in Children,” Current Opinion in Gastroenterology, Vol. 29, No. 1, 2013, pp. 31-38.

[5]   W. E. C. Moore and L. V. Holdeman, “Human Fecal Flora: The Normal Flora of 20 Japanese-Hawaiians,” Applied Microbiology, Vol. 27, No. 5, 1974, pp. 961-979.

[6]   P. B. Eckburg, E. M. Bik, C. N. Bernstein, et al., “Diversity of the Human Intestinal Microbial Flora,” Science, Vol. 308, No. 5728, 2005, pp. 1635-1638.

[7]   S. Cusack, M. J. Claesson and P. W. O’Toole, “How Beneficial Is the Use of Probiotic Supplements for the Aging Gut?” Aging Health, Vol. 7, No. 2, 2011, pp. 179186.

[8]   M. Kleerebezem and E. E. Vaughan, “Probiotic and Gut Lactobacilli and Bifidobacteria: Molecular Approaches to Study Diversity and Activity,” Annual Review of Microbiology, Vol. 63, 2009, pp. 269-290.

[9]   J. Xu J and J. I. Gordon, “Honor thy Symbionts,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 18, 2003, pp. 10452-10459.

[10]   D. N. Frank, A. L. St. Amand, R. A. Feldman, E. C. Boedeker, N. Harpaz and N. R. Pace, “Molecular-Phylogenetic Characterization of Microbial Community Imbalances in Human Inflammatory Bowel Diseases,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 34, 2007, pp. 13780-13785.

[11]   P. J. Turnbaugh, M. Hamady, T. Yatsunenko, et al., “A Core Gut Microbiome in Obese and Lean Twins,” Nature, Vol. 457, No. 7228, 2009, pp. 480-484.

[12]   R. E. Ley, F. Bäckhed, P. Turnbaugh, C. A. Lozupone, R. D. Knight and J. I. Gordon, “Obesity Alters Gut Microbial Ecology,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 31, 2005, pp. 11070-11075.

[13]   C. Palmer, E. M. Bik, D. B. DiGiulio, D. A. Relman and P. O. Brown, “Development of the Human Infant Intestinal Microbiota,” PLoS Biology, Vol. 5, No. 7, 2007, pp. 1556-1573.

[14]   R. A. Caicedo, R. J. Schanler, N. Li and J. Neu, “The Developing Intestinal Ecosystem: Implications for the Neonate,” Pediatric Research, Vol. 58, No. 4, 2005, pp. 625-628.

[15]   R. Ortega, A. Loria and R. Kelly, “A Semiglobally Stable P. L. Stark PL and A. Lee, “The Microbial Ecology of the Large Bowel of Breast-Fed and Formula-fed Infants during the First Year of Life,” Journal of Medical Microbiology, Vol. 15, No. 2, 1982, pp. 189-203.

[16]   J. Penders, C. Thijs, C. Vink, et al., “Factors Influencing the Composition of the Intestinal Microbiota in Early Infancy,” Pediatrics, Vol. 118, No. 2, 2006, pp. 511-521.

[17]   H. Garn, J. F. Neves, R. S. Blumberg and H. Renz, “Effect of Barrier Microbes on Organ-based Inflammation,” The Journal of Allergy and Clinical Immunology, Vol. 131, No. 6, 2013, pp. 1465-1478.

[18]   R. Jenness, “The Composition of Human Milk,” Seminars in Perinatology, Vol. 3, No. 3, 1979, pp. 225-239.

[19]   C. Lindner, B. Wahl, L. Föhse, et al., “Age, Microbiota and T Cells Shape Diverse Individual IgA Repertoires in the Intestine,” The Journal of Experimental Medicine, Vol. 209, No. 2, 2012, pp. 365-377.

[20]   E. Bezirtzoglou, A. Tsiotsias and G. W. Welling, “Microbiota Profile in Feces of Breastand Formula-Fed Newborns by Using Fluorescence in Situ Hybridization (FISH),” Anaerobe, Vol. 17, No. 6, 2011, pp. 478-482.

[21]   I. Adlerberth and A. E. Wold, “Establishment of the Gut Microbiota in Western Infants,” Acta Paediatrica, Vol. 98, No. 2, 2009, pp. 229-238.

[22]   J. J. Faith, J. L. Guruge, M. Charbonneau, et al., “The Long-term Stability of the Human Gut Microbiota,” Science, Vol. 341, No. 6141, 2013, in Press.

[23]   J. Jalanka-Tuovinen, A. Salonen, J. Nikkilä, et al., “Intestinal Microbiota in Healthy Adults: Temporal Analysis Reveals Individual and Common Core and Relation to Intestinal Symptoms,” PLoS One, Vol. 6, No. 7, 2011, Article ID: e23035.

[24]   C. D. Garland, A. Lee and M. R. Dickson, “Segmented Filamentous Bacteria in the Rodent Small Intestine: Their Colonization of Growing Animals and Possible Role in Host Resistance to Salmonella,” Microbial Ecology, Vol. 8, No. 2, 1982, pp. 181-190.

[25]   T. Baba and O. Schneewind, “Instruments of Microbial Warfare: Bacteriocin Synthesis, Toxicity and Immunity,” Trends in Microbiology, Vol. 6, No. 2, 1998, pp. 66-71.

[26]   M. Comalada, E. Bailón, O. de Haro, et al., “The Effects of Short-Chain Fatty Acids on Colon Epithelial Proliferation Andsurvival Depend on the Cellular Phenotype,” Journal of Cancer Research and Clinical Oncology, Vol. 132, No. 8, 2006, pp. 487-497.

[27]   A. J. Leonel and J. I. Alvarez-Leite, “Butyrate: Implications for Intestinal Function,” Current Opinion in Clinical Nutrition and Metabolic Care, Vol. 15, No. 5, 2012, pp. 474-479.

[28]   A. Thierry, S. M. Deutsch, H. Falentin, M. Dalmasso, F. J. Cousin and G. Jan, “New Insights into Physiology and Metabolism of Propionibacterium freudenreichii,” International Journal of Food Microbiology, Vol. 149, No. 1, 2011, pp. 19-27.

[29]   E. Husebye, P. M. Hellström and T. Midtvedt, “Intestinal Microflora Stimulates Myoelectric Activity of Rat Small Intestine by Promoting Cyclic Initiation and Aboral Propagation of Migrating Myoelectric Complex,” Digestive Diseases and Sciences, Vol. 39, No. 5, 1994, pp. 946-956.

[30]   B. P. Willing and A. G. Van Kessel, “Enterocyte Proliferation and Apoptosis in the Caudal Small Intestine is Influenced by the Composition of Colonizing Commensal Bacteria in the Neonatal Gnotobiotic Pig,” Journal of Animal Science, Vol. 85, No. 12, 2007, pp. 3256-3266.

[31]   H. Kozakova, J. Kolinska and Z. Lojda, “Effect of Bacterial Monoassociation on Brush-border Enzyme Activities in Ex-Germ-Free Piglets: Comparison of Commensal and Pathogenic Escherichia coli Strains” Microbes and Infection/Institute Pasteur, Vol. 8, No. 11, 2006, pp. 2629-2639.

[32]   T. W. Shirkey, R. H. Siggers, B. G. Goldade, et al., “Effects of Commensal Bacteria on Intestinal Morphology and Expression of Proinflammatory Cytokines in the Gnotobiotic Pig,” Experimental Biology and Medicine (Maywood, N.J.), Vol. 231, No. 8, 2006, pp. 1333-1345.

[33]   K. L. Madsen, J. S. Doyle, L. D. Jewell, M. M. Tavernini and R. N. Fedorak, “Lactobacillus Species Prevents Colitis in Interleukin 10 Gene-Deficient Mice,” Gastroenterology, Vol. 116, No. 5, 1999, pp. 1107-1114.

[34]   S. N. Ukena, A. Singh, U. Dringenberg, et al., “ Probiotic Escherichia coli Nissle 1917 inhibits leaky Gut by Enhancing Mucosal Integrity,” PLoS One, Vol. 2, No. 12, 2007, Article ID: e1308.

[35]   F. Lutgendorff, L. M. Akkermans and J. D. S?derholm, “The Role of Microbiota and Probiotics in Stress-Induced Gastro-Intestinal Damage,” Current Molecular Medicine, Vol. 8, No. 4, 2008, pp. 282-298.

[36]   E. Cario, G. Gerken and D. K. Podolsky, “Toll-Like Receptor 2 Controls Mucosal Inflammation by Regulating Epithelial Barrier Function,” Gastroenterology, Vol. 132, No. 4, 2007, pp. 1359-1374.

[37]   S. M. Collins and P. Bercik, “The Relationship between Intestinal Microbiota and the Central Nervous System in Normal Gastrointestinal Function and Disease,” Gastroenterology, Vol. 136, No. 6, 2009, pp. 2003-2014.

[38]   J. F. Cryan and T. G. Dinan, “Mind-Altering Microorganisms: The Impact of the Gut Microbiota on Brain and Behaviour,” Nature Reviews. Neuroscience, Vol. 13, No. 10, 2012, pp. 701-712.

[39]   Y. Song, C. X. Liu and S. M. Finegold, “Real-Time PCR Quantitation of Clostridia in Feces of Autistic Children,” Applied and Environmental Microbiology, Vol. 70, No. 11, 2004, pp. 6459-6465.

[40]   C. Atuma, V. Strugala, A. Allen and L. Holm, “The Adherent Gastrointestinal Mucus Gel Layer: Thickness and Physical state in Vivo,” American Journal of Physiology. Gastrointestinal and Liver Physiology, Vol. 280, No. 5, 2001, pp. 922-929.

[41]   M. E. Johansson, M. Phillipson, J. Petersson, A. Velcich, L. Holm and G. C. Hansson, “The Inner of the Two Muc2 Mucin-Dependent Mucus Layers in Colon is Devoid of Bacteria,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 39, 2008, pp. 15064-15069.

[42]   J. L. McAuley, S. K. Linden, C. W. Png, R. M. King, H. L. Pennington, S. J. Gendler, T. H. Florin, G. R. Hill, V. Korolik and M. A. McGuckin, “MUC1 Cell Surface Mucin Is a Critical Element of the Mucosal Barrier to Infection,” The Journal of Clinical Investigation, Vol. 117, No. 8, 2007, pp. 2313-2324.

[43]   H. Kawashima, “Roles of the Gel-Forming MUC2 Mucin and Its O-Glycosylation in the Protection against Colitis and Colorectal Cancer,” Biological and Pharmaceutical Bulletin, Vol. 35, No. 10, 2012, pp. 1637-1641.

[44]   E. C. Clark, S. D. Patel, P. R. Chadwick, G. Warhurst, A. Curry and G. L. Carlson, “Glutamine Deprivation Facilitates Tumour Necrosis Factor Induced Bacterial Translocation in Caco-2 Cells by Depletion of Enterocyte Fuel Substrate,” Gut, Vol. 52, No. 2, 2003, pp. 224-230.

[45]   C. L. Wells, E. M. VandeWesterlo, R. P. Jechorek and S. L. Erlandsen, “Effect of Hypoxia on Enterocyte Endocytosis of Enteric Bacteria,” Critical Care Medicine, Vol. 24, No. 6, 1996, pp. 985-991.

[46]   N. A. Hering, M. Fromm and J. D. Schulzke, “Determinants of Colonic Barrier Function in Inflammatory Bowel Disease and Potential Therapeutics,” The Journal of Physiology, Vol. 590, No. 5, 2012, pp. 1035-1044.

[47]   M. Schumann, S. Kamel, M. L. Pahlitzsch, L. Lebenheim, C. May, M. Krauss, M. Hummel, S. Daum, M. Fromm and J. D. Schulzke, “Defective Tight Junctions in Refractory Celiac Disease,” Annals of the New York Academy of Sciences, Vol. 1258, 2012, pp. 43-51.

[48]   S. Zeissig, N. Bürgel, D. Günzel, J. Richter, J. Mankertz, U. Wahnschaffe, A. J. Kroesen, M. Zeitz, M. Fromm and J. D. Schulzke, “Changes in Expression and Distribution of Claudin 2, 5 and 8 Lead to Discontinuous Tight Junctions and Barrier Dysfunction in Active Crohn’s Disease,” Gut, Vol. 56, No. 1, 2007, pp. 61-72.

[49]   Y. Ohashi, M. Hiraguchi, C. Sunaba, C. Tanaka, T. Fujisawa and K. Ushida, “Colonization of Segmented Filamentous Bacteria and Its Interaction with the Luminal IgA Level in Conventional Mice,” Anaerobe, Vol. 16, No. 5, 2010, pp. 543-546.

[50]   L. A. van der Waaij, P. C. Limburg, G. Mesander and D. van der Waaij, “In Vivo IgA Coating of Anaerobic Bacteria in Human Faeces,” Gut, Vol. 38, No. 3, 1996, pp. 348-354.

[51]   D. A. Peterson, N. P. McNulty, J. L. Guruge and J. I. Gordon, “IgA Response to Symbiotic Bacteria as a Mediator of Gut Homeostasis,” Cell Host & Microbe, Vol. 2, No. 5, 2007, pp. 328-339.

[52]   N. Shulzhenko, A. Morgun and W. Hsiao, et al., “Crosstalk between B Lymphocytes, Microbiota and the Intestinal Epithelium Governs Immunity versus Metabolism in the Gut,” Nature Medicine, Vol. 17, No. 12, 2011, pp. 1585-1593.

[53]   F. Pinheiro da Silva and M. C. Machado, “Antimicrobial Peptides: Clinical Relevance and Therapeutic Implications,” Peptides, Vol. 36, No. 2, 2012, pp. 308-314.

[54]   C. L. Wilson, A. J. Ouellette, D. P. Satchell, T. Ayabe, Y. S. López-Boado, J. L. Stratman, S. J. Hultgren, L. M. Matrisian and W. C. Parks, “Regulation of Intestinal Alpha-Defensin Activation by the Metalloproteinase Matrilysin in Innate Host Defense,” Science, Vol. 286, No. 5437, 1999, pp. 113-117.

[55]   N. H. Salzman, K. Hung, D. Haribhai, et al., “Enteric Defensins are Essential Regulators of Intestinal Microbial Ecology,” Nature Immunology, Vol. 11, No. 1, 2010, pp. 76-83.

[56]   Q. Li, C. Wang, C. Tang, N. Li and J. Li, “Molecular-phylogenetic Characterization of the Microbiota in Ulcerated and Non-ulcerated Regions in the Patients with Crohn’s Disease,” PLoS ONE, Vol. 7, No. 4, 2012, Article ID: e34939.

[57]   X. Y. Qiu, M. M. Zhang, X. T. Yang, N. Hong and C. G. Yu, “Faecalibacterium prausnitzii Upregulates Regulatory T cells and Anti-inflammatory Cytokines in Treating TNBS-induced Colitis,” Journal of Crohn’s & Colitis, 2013, in press.

[58]   H. Sokol, B. Pigneur, L. Watterlot, O. Lakhdari, L. G. Bermúdez-Humarán, J. J. Gratadoux, S. Blugeon, C. Bridonneau, J. P. Furet, G. Corthier, C. Grangette, N. Vasquez, P. Pochart, G. Trugnan, G. Thomas, H. M. Blottière, J. Doré, P. Marteau, P. Seksik and P. Langella, “Faecalibacterium prausnitzii Is an Anti-Inflammatory Commensal Bacterium Identified by Gut Microbiota Analysis of Crohn Disease Patients,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 43, 2008, pp. 16731-16736.

[59]   V. Strugala, P. W. Dettmar and J. P. Pearson, “Thickness and Continuity of the Adherent Colonic Mucus Barrier in Active and Quiescent Ulcerative Colitis and Crohn’s Disease,” International Journal of Clinical Practice, Vol. 62, No. 5, 2008, pp. 762-769.

[60]   E. Amit-Romach, R. Reifen and Z. Uni, “Mucosal Function in Rat Jejunum and Ileum Is Altered by Induction of Colitis,” International Journal of Molecular Medicine, Vol. 18, No. 4, 2006, pp. 721-727.

[61]   C. Moehle, N. Ackermann, T. Langmann, C. Aslanidis, A. Kel, O. Kel-Margoulis, A. Schmitz-Madry, A. Zahn, W. Stremmel and G. Schmitz, “Aberrant Intestinal Expression and Allelic Variants of Mucin Genes Associated with Inflammatory Bowel Disease,” Journal of Molecular Medicine, Vol. 84, No. 12, 2006, pp. 1055-1066.

[62]   M. Van der Sluis, B. A. De Koning, A. C. De Bruijn, et al., “Muc2-Deficient Mice Spontaneously Develop Colitis, Indicating that MUC2 Is Critical for Colonic Protection,” Gastroenterology, Vol. 131, No. 1, 2006, pp. 117-129.

[63]   L. Szentkuti, H. Riedesel, M. L. Enss, K. Gaertner and W. Von Engelhardt, “Pre-Epithelial Mucus Layer in the Colon of Conventional and Germ-Free Rats,” The Histochemical Journal, Vol. 22, No. 9, 1990, pp. 491-497.

[64]   C. Caballero-Franco, K. Keller, C. De Simone and K. Chadee, “The VSL#3 Probiotic Formula Induces Mucin Gene Expression and Secretion in Colonic Epithelial Cells,” American Journal of Physiology. Gastrointestinal and Liver Physiology, Vol. 292, No. 1, 2007, pp. 315-322.

[65]   M. T. Abreu, “Toll-Like Receptor Signaling in the Intestinal Epithelium: How Bacterial Recognition Shapes Intestinal Function,” Nature Reviews. Immunology, Vol. 10, No. 2, 2010, pp. 131-144.

[66]   L. Frolova, P. Drastich, P. Rossmann, K. Klimesova and H. Tlaskalova-Hogenova, “Expression of Toll-Like Recaptor 2 (TLR2), TLR4, and CD14 in Biopsy Samples of Patients with Inflammatory Bowel Diseases: Upregulated Expression of TLR2 in Terminal Ileum of Patients with Ulcerative Colitis,” The Journal of Histochemistry and Cytochemistry, Vol. 56, No. 3, 2008, pp. 267-274.

[67]   N. Kamada, T. Hisamatsu, S. Okamoto, H. Chinen, T. Kobayashi, T. Sato, A. Sakuraba, M. T. Kitazume, A. Sugita, K. Koganei, K. S. Akagawa and T. Hibi, “Unique CD14 Intestinal Macrophages Contribute to the Pathogenesis of Crohn Disease via IL-23/IFN-gamma Axis,” The Journal of Clinical Investigation, Vol. 118, No. 6, 2008, pp. 2269-2280.

[68]   S. Rakoff-Nahoum, J. Paglino, F. Eslami-Varzaneh, S. Edberg and R. Medzhitov, “Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis,” Cell, Vol. 118, No. 2, 2008, pp. 229-241.

[69]   K. L. Edelblum, M. K. Washington, T. Koyama, S. Robine, M. Baccarini and D. B. Polk, “Raf Protects against Colitis by Promoting Mouse Colon Epithelial Cell Survival through NF-KappaB,” Gastroenterology, Vol. 135, No. 2, 2008, pp. 539-551.

[70]   J. P. Hugot, M. Chamaillard, H. Zouali, et al., “Association of NOD2 Leucine-Rich Repeat Variants with Susceptibility to Crohn’s Disease,” Nature, Vol. 411, No. 6837, 2001, pp. 599-603.

[71]   A. Rehman, C. Sina, O. Gavrilova, R. H?sler, S. Ott, J. F. Baines, S. Schreiber and P. Rosenstiel, “Nod2 Is Essential for Temporal Development of Intestinal Microbial Communities,” Gut, Vol. 60, No. 10, 2011, pp. 1354-1362.

[72]   J. Wehkamp, N. H. Salzman, E. Porter, S. Nuding, M. Weichenthal, R. E. Petras, B. Shen, E. Schaeffeler, M. Schwab, R. Linzmeier, R. W. Feathers, H. Chu, H. Lima Jr., K. Fellermann, T. Ganz, E. F. Stange and C. L. Bevins, “Reduced Paneth Cell Alpha-Defensins in Ileal Crohn’s Disease,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 50, 2005, pp. 18129-18134.

[73]   T. Watanabe, A. Kitani, P. J. Murray, Y. Wakatsuki, I. J. Fuss and W. Strober, “Nucleotide Binding Oligomerization Domain 2 Deficiency Leads to Dysregulated TLR2 Signaling and Induction of Antigen-Specific Colitis,” Immunity, Vol. 25, No. 3, 2006, pp. 473-485.

[74]   T. Watanabe, N. Asano, P. J. Murray, K. Ozato, P. Tailor, Ivan J. Fuss, A. Kitani1 and W. Strober, “Muramyl Dipeptide Activation of Nucleotide-Binding Oligomerization domain 2 Protects Mice from Experimental Colitis,” The journal of Clinical Investigation, Vol. 118, No. 2, 2008, pp. 545-549.

[75]   S. Sepehri, R. Kotlowski, C. N. Bernstein and D. O. Krause, “Microbial Diversity of Inflamed and Noninflamed Gut Biopsy Tissues in Inflammatory Bowel Disease,” Inflammatory Bowel Diseases, Vol. 13, No. 6, 2007, pp. 675-683.