Colonic Immune Function and Colonic Bacterial Flora

The immune system of the gastrointestinal tract defends against infection (bacterial, viral, and parasitic) and luminal antigens ingested/formed by bacteria. Nonspecific and specific mechanisms exist.

The mucin secreted by colonic goblet cells serves a barrier function for the mucosal surface. Mucosal integrity is an important barrier to luminal pathogens. Interepithelial cell junctions function both to control permeability as pertains to fluid and electrolyte absorption and to prevent pathogen access beyond this layer.

The enteric immune system is vast and complex; it interacts with the rest of the immune system as well as with luminal contents. Gut-associated lym-phoid tissue consists of both discretely organized tissue, such as Peyer's patches (lymphoid follicles with proliferative potential in response to antigen presentation) containing M cells, and the more diffuse lymphocytes and macrophages distributed among the submucosa, mucosa, and lamina propria (Figure 6). M cells function in antigen sampling of

LUMEN

EPITHELIUM

__^^ Intraluminal

C)J lymphocyte firmnnnjuirinAnmrr

Intraepithelial lymphocyte firmnnnjuirinAnmrr

EPITHELIUM

M cell M cell associated lymphocyte

M cell M cell associated lymphocyte

LAMINA PROPRIA

/ Peyer's Patch Macrophage 1 lymphocytes

§ Lymphocytes

§ Lymphocytes

Figure 6 Mucosal immunology. (Reproduced with permission from Shils ME, Olson JA, Shike M, and Ross AC (1999) Modern Nutrition in Health and Disease, 9th edn. Baltimore: Lippincott Williams & Wilkins.)

intraluminal contents by binding antigens, endocyto-sis, antigen processing, and subsequent interaction with lymphocytes and macrophages within Peyer's patches, eliciting host responses. The lymphocyte complement of Peyer's patches originate in either the bone marrow or the thymus, enter the systemic circulation to migrate to Peyer's patches, interact, return to the intestinal mucosa or, via mesenteric lymph nodes, re-enter the systemic circulation to other organs.

The gastrointestinal tract houses up to 80% of the body's immunoglobulin-producing cells. Intra-epithelial T lymphocytes, plasma cells, macrophages, dendritic cells, eosinophils, and mast cells also function in a specialized manner (Figure 7).

Secretory IgA is an important host immune defense mechanism. Unlike the monomeric, systemic form of IgA, intestinal secretory IgA is polymeric (specifically, dimeric) in nature. This dimeric immunoglobulin is secreted by B lymphocytes situated in the lamina propria, and it contains a unique 'J' chain instrumental in polymer formation. This IgA binds to the Ig receptor of the epithelial cell on the basolateral membrane and, following endocytosis and transport across the cell, is secreted from the apical side.

Secretory IgA binds to intraluminal antigens, including dietary ones, and functions in preventing their absorption. Additionally, secretory IgA has the ability to bind to microorganisms, thus preventing adherence, colonization, and invasion. Secretory IgA is secreted in breast milk, and in breast-fed neonates and infants it confers a degree of passive immunity to infection by limiting luminal contents from interacting with, or directly binding to or invading, the mucosa.

Interaction of intraluminal bacteria with the immune system may affect intestinal permeability, and it may modulate the intestinal immune system. Certain bacterial species are believed to interact with other enteric flora as well as with the host immune system to effect a healthier gastrointestinal tract and enhance nutrient digestion. Organisms studied include Lactobacillus, Vibrio species, and sacro-myces. These findings, among others beneficial to the host, have prompted investigation into oral supplementation of single and multiple species of these probiotics for prevention and treatment of antibiotic-associated diarrhea, bacterial overgrowth in short bowel syndrome, and as an adjuvant therapy for inflammatory bowel disease, as well as for the treatment and prevention of recurrent clostri-dium difficile colitis.

Regulation of the quantity of bacteria, in addition to the specific profile of bacterial species present, is dependent on a host of factors, including gastric acid output, gastrointestinal motility, luminal contents, and the milieu created therein. Additionally, the intraluminal environmental milieu is affected by the specific properties of different species of bacteria and their interactions with other luminal species and with the host.

The colon accommodates the largest number of enteric flora, on the order of 1010-1012—more than 100 000 flora and more than 100-fold greater diversity of species than in any other location in the alimentary canal. Efflux of bacteria into the ileum is hindered by the ileocecal valve, which functions to restrict several of these bacterial species to the large intestine. The majority of these colonic bacteria are anaerobic in nature (Table 3).

Table 3 Colonic enteric flora

Bacterial genus

Prevalence

Total count

(%)

(CFU/gorml)

Anaerobes

109-1012

Bacteroides

100

Porphyromonas

100

Bifidobacterium

30-70

Lactobacillus

20-60

Clostridium

25-35

Peptostreptococcus

Peptococcus

Methanogens

Facultative aerobes

102-109

Enterococcus

100

Escherichia coli

100

Staphylococcus

30-50

Other

40-80

Enterobacteriaceae

Table 4 Examples of biochemical reactions by intestinal flora

Reaction type

Reaction

Example substrate

Hydrolysis

Amides

Methotrexate

Glucuronides

Estradiol-3-glucuronide

Dehydroxylation

Decarboxylation

Amino acids

Deamination

Amino acids

Dehydrogenase

Bile acids, cholesterol

Reduction

Double bonds

Unsaturated fatty acids

Acetylation

Histamine

From Klein S, Cohn SM and Alpers DH (1999) The alimentary tract in nutrition. In: Modern Nutrition in Health & Disease, 9th edn, pp. 605-631. Baltimore: Williams & Wilkins.

From Klein S, Cohn SM and Alpers DH (1999) The alimentary tract in nutrition. In: Modern Nutrition in Health & Disease, 9th edn, pp. 605-631. Baltimore: Williams & Wilkins.

The enteric flora plays several important roles. It interacts with the enteric immune system, effecting cellular immune activity; it is associated with the size and number of Peyer's patches present, influencing intestinal motility; and it has nutritively important functions, including bile salt deconjugation (facilitating enterohepatic circulation of bile salts), bilirubin metabolism (deconjugation and urobilin formation, allowing excretion), mucin degradation, and lipid metabolism (generation of short-chain fatty acids). Androgens and estrogens are hydro-lyzed, facilitating resorption and conservation of these sterols, whereas cholesterol is processed into coprostanol, a nonabsorbed sterol. Ammoniagenesis via protein and urea degradation may play a role in hepatic encephalopathy (Table 4).

Consumption of lipids, carbohydrates, and protein also occurs by colonic bacteria, in addition to that of vitamins (vitamin B12 and folic acid are consumed; vitamin K and biotin are produced by these bacteria).

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