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Traveler's diarrhea, a common condition caused by consuming contaminated food or water, is primarily attributed to a heat-stable toxin produced by Escherichia coli known as STa. This toxin specifically binds to guanylyl cyclase C (GC-C) receptors located on the surface of intestinal epithelial cells. Consequently, GC-C generates a substantial amount of intracellular cyclic guanosine monophosphate (cGMP), which in turn activates the cystic fibrosis transmembrane conductance regulator (CFTR) chloride (Cl-) channel. Activation of CFTR leads to increased secretion of Cl- ions. It is worth questioning why humans possess a receptor for this toxin in a location accessible to luminal bacteria and their products. This curiosity gave rise to the hypothesis that GC-C might have a natural ligand with a physiological role. Subsequent research identified and purified guanylin, a hormone synthesized in the intestine, as the native ligand for GC-C. Another related molecule called uroguanylin, secreted by the kidney, also plays a crucial role in regulating salt and water homeostasis in the body. While STa shares structural similarities with guanylin, it has modifications that allow it to persist in the intestinal lumen for extended periods. This exemplifies molecular mimicry, where a bacterial product exploits a receptor and its associated signaling for its own purposes, presumably to propagate the toxin-producing bacteria to additional hosts.

In addition to its role in traveler's diarrhea, the colonic microbiota significantly contributes to the production of intestinal gas. Although some air is swallowed during meals, most of it is expelled through burping. However, the microbiota ferments unabsorbed dietary components, resulting in the production of substantial volumes of nitrogen, hydrogen, and carbon dioxide. Each day, around 1 liter of these nonodorous gases, including methane in some cases, is excreted through the anus, even in individuals who do not experience flatulence. While trace amounts of odorous compounds like hydrogen sulfide, indole, and skatole are also present, they are minimal.

The final step in the digestion process is the elimination of indigestible residues from the body through defecation. Feces consist not only of these residues but also contain dead bacteria, desquamated epithelial cells from the intestinal lining, biliary metabolites specifically targeted for excretion, and a small amount of water. In healthy individuals, stool contains very few, if any, useful nutrients. The presence of nutrients, especially lipid (referred to as steatorrhea), indicates a condition of maldigestion, malabsorption, or both. The presence of fat in the stool is particularly indicative of small intestinal dysfunction since the colonic microbiota poorly utilizes it. However, loss of carbohydrate and protein in the stool can also occur if the underlying condition worsens.

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Atoxinknownasheat-stable toxin of E. coli, orSTa,isamajorcausativeagentoftraveler’sdiarrhea,whichcanbecontractedbyconsumptionofinfectedfoodorwater.Thistoxinbindstoareceptorontheapicalsurfaceofintestinalepithelialcellsknownasguanylyl cyclase C (GC-C).Inturnthisenzymegenerateslargequantitiesofintracellularcyclicguanosinemonophosphate(cGMP)thattriggerincreasedCl− secretionviaactivationofthecysticfibrosistransmembraneconductanceregulator(CFTR)Cl− channel.However,onecouldofcoursequestionwhyhumansexpressareceptorforthistoxininasitethatwouldbeaccessibletoluminalbacteriaandtheirproducts.Indeed,thisledtothehypothesisthatthereisanativeligandforGC-Cthatcouldplayaphysiologicalrole.Researcherssubsequentlypurifiedandidentifiedguanylin,ahormonesynthesizedintheintestine.Togetherwitharelatedmolecule,uroguanylin,secretedbythekidney,guanylinisanimportantregulatorofsaltandwaterhomeostasisinthebody.STahasstructuralsimilaritiestoguanylin,butithasmodificationsthatpermitittopersistintheintestinallumenforprolongedperiods.Thisisanexampleofmolecularmimicry,inwhichabacterialproducthijacksareceptorandassociatedsignalingforitsownpurposes(presumablytopropagatethetoxin-producingbacteriatoadditionalhosts).
The colonic microbiota is also notable for its contribution to formation of intestinal gas. Although large volumes of air may be swallowed in conjunction with meals, the majority of this gas returns up the esophagus via belching. However, during fermentation of unabsorbed dietary components, the microbiota generates large volumes of nitrogen, hydrogen, and carbon dioxide. Approximately 1 L of these nonodorous gases is excreted on a daily basis via the anus in all individuals, even those who do not complain of flatulence. Some individuals may generate appreciable concentrations of methane. Trace amounts of odorous compounds are also present, such as hydrogen sulfide, indole, and skatole.
The final stage in the journey taken by a meal after its ingestion is expulsion of its indigestible residues from the body in the process known as defecation. The feces also contain the remnants of dead bacteria, dead and dying epithelial cells that have been desquamated from the lining of the intestine, biliary metabolites specifically targeted for excretion (e.g., conjugates of xenobiotics [see ]), and a small amount of water. In health, the stool contains few if any useful nutrients. The presence of nutrients in stool, particularly lipid (known as steatorrhea), signifies maldigestion, malabsorption, or both. Fat in the stool is a sensitive marker of small intestinal dysfunction because it is poorly used by the colonic microbiota, but loss of carbohydrate and protein in stool can also be seen if the underlying condition worsens.