Humans develop the disease cholera after ingesting water or food contaminated with the bacterium Vibrio cholerae. In parts of the world where cholera appears in a yearly cycle (endemic areas), V. cholerae is constantly present in the environment even when there is no disease. During cholera epidemics the microorganisms are acquired by human hosts and rapidly transmitted via the fecal-oral route from person to person.

When swallowed, V. cholerae colonizes the surface (epithelium) of the small intestine by using specialized adherence structures called toxin co-regulated pili or mannose-sensitive hemagglutinins (the sugar mannose specifically inhibits attachment in vitro). Then the vibrios release a potent enterotoxin that causes enterocytes to temporarily reverse their normal absorptive function and instead hypersecrete water and electrolytes. The resultant voluminous diarrhea can lead to lethal dehydration (cholera gravis); but because the infection is self limited (localized and short term), patients can be treated by simply using oral or intravenous fluid replacement.

Antibiotic treatment is not necessary, but it is often employed to eliminate vibrio shedding into the environment and to decrease the amount of replacement fluids required. Unfortunately, high mortality from cholera occurs in developing countries with inadequate treatment facilities.