PROFESSIONAL RESOURCES The Microenvironment of the Colonic Cell and Bacterial Flora Barry Goldin, PhD Tufts University School of Medicine The human gastrointestinal (GI) tract is a complex ecosystem populated by at least 400 strains of bacteria that collectively make up the intestinal microflora. There is increasing appreciation that the intestinal microflora play an important role in health and disease through their effects on metabolism and absorption of nutrients, modulation of immune function and prevention of inflammation. Although the microorganisms that inhabit the GI tract have not been completely quantified and described, the major species and approximate numbers are shown in Table 1. Bacteria are quantified as the number of bacteria present per milliliter of intestinal contents. They are also sometimes quantified in CFU (colonizing fecal units), the concentrations of bacteria per gram of intestinal contents. Table 1. Composition of the human oropharyngeal and gastrointestinal microflora* * Number of organisms per millileter of intestinal contents The gastrointestinal system consists of the following compartments: oral cavity; esophagus; stomach; small intestine (duodenum, jejunum, ileum) and large intestine (cecum, colon, rectum). The bacterial population of these compartments varies both in type and mass and tends to increase, particularly the anaerobic types, with distance from the oral cavity. Esophagus - has no indigenous microbes but is populated by microbes from food and the oral cavity Stomach - contains about 104 CFU/gram of microorganisms including candida albicans, helicobacter pylori, lactobacillus and streptococcus Duodenum - contains about 103-104 CFU/gram of microorganisms including bacteroides, candida albicans, lactobacillus and streptococcus Jejunum - contains about 105-107 CFU/gram of microorganisms including bacteroides, candida albicans, lactobacillus and streptococcus Ileum - contains about 107-108 CFU/gram of microorganisms including bacteroides, clostridium, enterobacteriaceae, enterococcus, lactobacillus and veillonella Colon - contains about 105-107 CFU/gram of microorganisms including bacteroides, bacillus, bifidobacteria, enterococcus, eubacterium, fusobacterium, peptostreptobacterium, ruminococcus and streptococcus The GI tract is sterile at birth but is rapidly colonized by microorganisms to which the infant is exposed during birth and breastfeeding. By the age of three months the profile of the intestinal microflora resembles that of adults. Bacteria are able to bind to special glycoconjugate receptors on GI epithelial cells, where they participate in a wide variety of biochemical reactions with a wide variety of substrates. One of their basic protective roles is resistance to new colonization by potentially pathogenic microorganisms, probably through competition for nutrients and attachment sites. Several factors determine the microbial concentrations of the GI tract, including the gastric acid in the stomach, bile acids in the intestines, and propulsive motility of the intestines. Concentrations of bacteria are low in the stomach because of its high acidity. Concentrations increase progressively through the small intestine, but overgrowth is prevented by small bowel motility. In the colon, bacterial concentrations increase dramatically. The bacterial composition of the intestinal microflora reflects to some degree the composition of the diet. For example, a comparison of the microflora of vegetarians, Japanese who consume an Asian diet with fish but no beef, and subjects consuming a Western diet including beef showed markedly different proportions in several aerobic and anaerobic strains, yeasts and fungi, although the total CFU counts were comparable for all groups. Within an individual, however, the microflora are very stable throughout life. Functions of the GI Microflora The GI microflora play a number of roles that have an impact on health, including control of bacterial growth; salvage of energy, control of epithelial proliferation, metabolism of xenobiotics, immunostimulation, resistance to infection, control of the colonic pH, and control of transit time and motility. The final steps in digestion and absorption of carbohydrates, proteins and fats occur at the level of the intestinal epithelial cell, where the GI flora are also involved in a variety of important processes. The actions of normal microflora on dietary substances include: Carbohydrates are fermented to yield short chain organic acids, hydrogen and carbon dioxide. Proteins and amino acids are degraded to intermediate end products tryptophan, glycine and methionine, which in turn yield indoles, ammonia, and hydrogen sulfide and dimethyl sulfide, respectively. Fatty acids are hydroxylated into oleic acid and finally to hydroxystearic acid. The microflora also react with endogenous substances such as urea, bilirubin, conjugated bile salts and bile salts. Urea is hydrolyzed to form ammonia; bilirubin is reduced to urobilirubin. Conjugated bile salts are deconjugated (separated from glycine or taurine) to form bile salts; bile salts are dehydroxylated to form various secondary bile salts such as deoxycholic acid and lithocholic acid. Finally, the GI microflora have nutritional effects. Certain bacteria are involved in the synthesis of vitamin K - important for blood clotting and for bone health - and folic acid, which is important for DNA synthesis. Vitamin B12, on the other hand, is bound to bacteria and excreted. In addition, the intestinal microflora participate in the metabolism of drugs, supplements and additives, including estrogens, cyclamate, caffeine, morphine, DOPA, warfarin and other substances. In the colon, the microflora defend against pathogens in several ways. Fermentation of the undigested food that arrives in the colon produces the short-chain fatty acids (SCFA) butyrate, proprionate and acetate, which decrease the luminal pH. Additionally, the microflora produce antibacterial substances. Together these influences act to destroy pathogenic organisms in the colon, thus influencing the nature and number of microbes. Influence of Intestinal Microflora on Immunity The intestinal microflora are critical for the proper functioning of the immune system of the gut, which is an important component of the body's total immune capacity. The first line of defense is a barrier function: by occupying the available epithelial attachment sites and more successfully competing for essential nutrients, the microflora block invasion by pathogens. Secondly, they produce antimicrobial compounds, volatile fatty acids and modified bile acids than discourage the growth of pathogens. Lastly, they influence both innate and adaptive immunity through their ability to communicate with lymphocytes that inhabit the intestinal epithelial and mucosal tissues. The intestinal immune system consists of a complex network of interacting cell populations in three major compartments: The GALT (gut associated lymphoid tissue) consists of aggregates of nonencapsulated lymphoid tissue found at intervals along the length of the small intestine, including areas called "Peyer's patches" that produce dendritic cells, T cells and B cells. The lamina propria is a layer of connective tissue just beneath the intestinal epithelium that is endowed with B cells that are capable of secreting the antibody immunoglobulin A (IgA). The epithelium itself, the layer of cells lining the intestines, contains specialized M cells that are capable of transporting antigens through the epithelium and presenting them to the lymphocytes in the lamina propria. In addition, the epithelium contains goblet cells that secrete mucus and Paneth cells that secrete antimicrobial proteins and peptides in response to signals from the microflora. The major players in the innate immune function in the intestine include mucus, intestinal epithelial cells, M cells, lymphocytes, goblet cells, Paneth cells, Peyer's patches and the lamina propria. Antigens traveling through the intestine are sampled and presented to the B and T cells of the adaptive immune system via three pathways - the dendritic cell pathway, the M cell pathway and the enterocyte pathway. The immature B and T cells in the Peyer's patches learn to recognize these antigens. Eventually they exit the Peyer's patch and guard against microbes by patrolling the subepithelial regions throughout the intestine. Among the weapons in their arsenal are cytokines and chemokines that can be either pro- or anti-inflammatory. The gut immune system plays a dual role in that it not only provides defense against infectious agents, but also learns to tolerate harmless food and microbial antigens. This discriminatory ability is influenced by exposure to microbes early in life and is a critical function. When the immune system is not properly conditioned to tolerate harmless substances, it may mount inappropriate defenses that are experienced as allergies and autoimmune diseases. The Role of Probiotics A probiotic is defined as a live microbial feed supplement that beneficially affects the host by improving its intestinal microbial balance. In lay terms, probiotics are known as the "friendly bacteria" present in fermented foods such as yogurt, buttermilk, cheese, whey, and also in supplemental capsules and powders. By strengthening the immune capabilities of the intestine, probiotics are believed to have a variety of health benefits. Evidence is strongest for the alleviation of gastroenteritis and certain kinds of diarrhea, particularly diarrhea associated with antibiotic use, diarrhea caused by retrovirus in infants and children; and recurrence of relapsing diarrhea due to Clostridum difficile. There is also evidence of benefit in lactose intolerance, irritable bowel syndrome, Crohn's disease, ulcerative colitis, certain cancers, helicobacter pylori infection, and infant food allergies. Because the mucosal immune system is common not only to the intestine but also to other mucosal tissues such as the genitourinary tract and the oral cavity, some studies have found probiotic benefits against urinary tract infections and even dental caries. Most of these claims are not supported by double-blind, placebo-controlled trials in humans, but there is substantial in vitro and animal evidence, and a growing body of clinical data. As more is learned about the mechanics of the intestinal immune system and the immunomodulatory effects of specific bacteria, targets for probiotic therapy may be more accurately defined and tested. It is possible that at some date in the future, "designer" probiotics may be developed for a host of individual needs. « Back to list of Summaries Sitemap | Terms & Conditions/Privacy Policy | Contact Us