Diarrheal diseases, which result from inadequate access to clean food and water, are a major cause of infant mortality worldwide. These diseases also cause significant suffering and occasional deaths in developed countries, imposing a substantial economic burden. Infectious diarrhea is triggered by various organisms, some of which, like cholera or pathogenic strains of Escherichia coli, produce toxins that stimulate excessive Cl− secretion in intestinal epithelial cells. Diarrhea can also occur when nutrients are not properly digested and absorbed in the small intestine, such as in lactose intolerance, or due to colonic inflammation. In most cases of diarrhea, colonic NaCland Na+ absorption is downregulated while Cl− secretion is stimulated, exacerbating fluid loss. However, nutrient-linked Na+ absorptive processes typically remain intact. This explains the effectiveness of oral rehydration solutions, which contain prepackaged mixtures of salt and glucose. Na+ and glucose uptake from these solutions, mediated by SGLT1, restores fluid absorption. These solutions save lives in areas where diarrhea is prevalent and access to sterile intravenous solutions for rehydration is limited or nonexistent.

While the colonic microbiota is not essential for life, animals raised in germ-free conditions appear to develop normally and reproduce. However, these animals have an immature mucosal immune system and slower differentiation of intestinal epithelial cells. Nonetheless, the colonic microbiota provides several benefits to the host. The constituent microbes perform metabolic reactions that mammalian cells cannot. Bacterial enzymes act on both endogenous and exogenous substrates, forming secondary bile acids and deconjugating bile acids for reabsorption. They also convert bilirubin into urobilinogen and salvage nutrients, like dietary fiber, that are resistant to pancreatic and brush border hydrolases. The metabolic contributions of the colonic microbiota are summarized in Table 31.1. Microbial metabolism can also be harnessed for pharmacological purposes, such as designing drugs that become bioavailable only after being acted on by bacterial enzymes. Additionally, bacterial enzymes may detoxify certain dietary carcinogens but can also generate toxic or carcinogenic compounds from dietary substrates.

Commensal microorganisms play a crucial role in limiting the growth or invasion of pathogenic microorganisms. They accomplish this through various mechanisms, including the synthesis and secretion of compounds that inhibit competitor organisms or have microbicidal effects. Commensal microorganisms also act as a physical barrier, preventing the attachment of pathogens and their entry into colonic epithelial cells. Furthermore, they trigger gene expression patterns in the epithelium that counteract the adverse effects of pathogens on epithelial function. These mechanisms help explain why patients who receive broad-spectrum antibiotics, which temporarily disrupt the colonic microbiota, are susceptible to overgrowth of pathogenic organisms and subsequent intestinal and systemic infections. Additionally, these mechanisms shed light on the efficacy of probiotics, which are commensal bacteria intentionally ingested to prevent or treat various digestive disorders.
Diarrhealdiseasesareamajorcauseofinfantmortalityworldwideandareusuallytheresultofinadequateaccesstocleanfoodandwater.Evenindevelopedcountries,diarrhealdiseasescausesubstantialsufferingandoccasionalwell-publicizeddeathsandcarryasubstantialeconomicburdenbecauseoftheirprevalence.Infectiousdiarrheaiscausedbyanumberoforganisms,withseveral(e.g.,choleraorpathogenicstrainsofEscherichia coli)capableofelaboratingtoxinsthattriggerexcessiveincreasesinactiveCl− secretionbysmallandlargeintestinalepithelialcells.Diarrheacanalsoresultwhennutrientsarenotappropriatelydigestedandabsorbedinthesmallintestine(e.g.,lactoseintolerance)orasaresultofcolonicinflammation.Inmostdiarrhealdiseases,colonicNaClandNa+ absorptionaredownregulatedatthesametimeCl− secretionmaybestimulated,thusfurtherworseningfluidloss.Ontheotherhand,nutrient-linkedNa+ absorptiveprocessestypicallyremainintact.Thisprovidestherationalefortheeffectivenessoforalrehydrationsolutions,whichareprepackagedmixturesofsaltandglucose.UptakeofNa+ andglucosefromthesesolutions,mediatedbySGLT1(see ),restoresfluidabsorption.Thesesolutionssavelivesinareaswherediarrheaisprevalentandtheabilitytorehydratepatientswithsterileintravenoussolutionsislimitedorabsent.
The colonic microbiota is not essential to life because animals raised in germ-free conditions apparently develop normally and are able to reproduce. However, in such animals the mucosal immune system is immature, and intestinal epithelial cells differentiate more slowly. Importantly the colonic microbiota provides benefits to the host in that the constituent microbes are capable of performing metabolic reactions that do not take place in mammalian cells. Bacterial enzymes act on both endogenous and exogenous substrates. They form secondary bile acids and deconjugate bile acids that have escaped uptake in the terminal ileum, so they can be reabsorbed. They convert bilirubin into urobilinogen (see ) and salvage nutrients that are resistant to pancreatic and brush border hydrolases, such as dietary fiber. A summary of the metabolic contributions of the colonic microbiota is provided in
Table 31.1 . Microbial metabolism can also be exploited for pharmacological purposes. A drug targeted to the colon, for example, can be conjugated in such a way that it will become bioavailable only after it is acted on by bacterial enzymes. Bacterial enzymes may also detoxify some dietary carcinogens, but equally they may generate toxic or carcinogenic compounds from dietary substrates.
Commensal microorganisms also play a critical role in limiting the growth or invasion (or both) of pathogenic microorganisms. They fulfill this antimicrobial role via a number of different mechanisms—by synthesizing and secreting compounds that inhibit the growth of competitor organisms or that are microbicidal, by functioning as a physical barrier to prevent attachment of pathogens and their subsequent entry into colonic epithelial cells, and by triggering patterns of gene expression in the epithelium that counteract the adverse effects of pathogens on epithelial function. These mechanisms provide a basis for understanding why patients who have received broad-spectrum antibiotics, which temporarily disrupt the colonic microbiota, are susceptible to overgrowth of pathogenic organisms and associated intestinal and systemic infections. They may also shed light on the efficacy of probiotics, commensal bacteria selected for their resistance to gastric acid and proteolysis that are intentionally ingested to prevent or treat a variety of digestive disorders.