Bacteria colonize the colon because it contains elements that are critical for their growth: a warm, moist, stable environment with an abundant supply of nutrients both of exogenous (ie, dietary) and endogenous (ie, sloughed cells, mucus, secretions) origin. The resulting flora is among the most diverse in nature, incorporating over 400 different species of bacteria. It is replenished at a rate of 150 to 400 g daily, with each gram containing more than 1011 organisms.
Development of this complex ecosystem begins at birth. Initially, the colon is sterile and has a pH of 6.5 to 7.0. Within hours after birth, aerobes and facultative anaerobes (eg, Escherichia coli and Streptococcus) colonize to levels of 106 to 108 organisms per gram of feces. This results in an environment that is increasingly reduced in oxygen and thus favors the growth of strict anaerobes.
In breast-fed infants, Bifidobacterium appears by day 4 to 7, reaching levels of 108 to 1011 organisms per gram. Clostridium, Lactobacillus, and even Bacteroides also may colonize at this time. The presence of these organisms is associated with an acidic luminal pH of 5.1.
It has been noted that Bifidobacterium produces primarily lactate and acetate via lactose fermentation. The resulting milieu has been suggested to retard the growth of pathogenic bacteria such as E. coli and Salmonella and to promote the growth of Bifidobacterium.
In bottle-fed infants, the initial metabolic events differ. Strains of enterobacteria such as E. coli and Klebsiella pneumoniae predominate in a relatively neutral pH environment. By the end of the second week, in both breast- and bottle-fed infants, the rapid fluctuations both in bacterial numbers and in bacterial metabolic end products stabilize, and Bifidobacterium, Eubacterium, Clostridium, and Lactobacillus become the predominant species. This balance is maintained throughout adult life.
Under normal conditions, the presence of bacteria enhances colonic function. The primary nutrients for bacterial metabolism are carbohydrates, which are rapidly fermented to short-chain fatty acids (SCFAs, eg, acetate, butyrate, propionate) and gases (eg, hydrogen, carbon dioxide, methane). The SCFAs, which are the predominant colonic anions, are readily absorbed across the mucosa and indirectly coupled to sodium uptake. Water passively follows the absorption of the anions. Thus, SCFA absorption acts as a primary stimulus for colonic salt and water absorption. In addition, SCFAs comprise an essential energy resource for the colonic epithelium. Butyrate provides the primary fuel for the colonocytes, whereas acetate and propionate serve as fuels for systemic needs, thus salvaging carbohydrate energy that otherwise would be lost in feces. The lack of steady SCFA uptake and metabolism may explain the clinical condition termed diversion colitis, which occurs in colon pouches following creation of ostomies (see Sec. 17.21.5). The relationship between the colon and its flora is further apparent from the morphologic and physiological changes that occur when the colon is devoid of bacteria. In the germ-free state, the cecum enlarges, and the colon wall, especially the mucosal layer, thins. Whereas the normal colon is absorptive, assimilating 1.5 to 2.0 L of fluid and 275 mEq of sodium per day, the gnotobiotic colon is secretory. In the germ-free state, malabsorption of any nutrient results in brisk osmotic diarrhea. Similarly, when broad-spectrum antibiotics are administered, the normal flora can be eradicated, reducing their metabolic capacity, and this results in osmotic diarrhea.
Mounting evidence indicates that some probiotics can modify the course of infectious or traveler’s diarrhea. The most studied probiotic has been lactobacilli, especially Lactobacillus GG. Lactobacilli have been noted to reduce fluid losses during rotavirus-induced diarrhea, to prevent its spread within a hospital setting, and to protect against acquisition of rotavirus in relatively malnourished toddlers. However, not all probiotics have been found to be effective in viral disease. And even those that do modify viral-induced diarrhea have failed to curb invasive bacterial diarrhea. It has been suggested that, besides differences between probiotic species in their clinical effectiveness, another reason for variability between patients is a lack of quality control. One study showed almost no correlation between package claims and actual bacterial content of the products.
The presence of bacteria in the large intestine provides a nutritional aid for the host and a barrier to pathogenic organisms, but following the administration of broad-spectrum antibiotics, the normal flora can be depleted, leading to overgrowth of opportunistic toxigenic bacteria, especially Clostridium difficile, which can induce a secretory and inflammatory diarrhea termed pseudomembranous colitis. Recent evidence also supports giving the probiotics Lactobacillus GG or Saccharomyces boulardii when antibiotics are prescribed in order to prevent subsequent bacterial overgrowth with C. difficile, especially in those prone to chronic C. difficile infection. Several other species of probiotics have demonstrated efficacy in either treating or preventing the other complications that can be associated with antibiotic use.