E. coli colonize the human gastrointestinal tract. The temperature of that environment is tightly regulated. However, the pH ranges from the highly acidic stomach (pH 4.5) to the relatively basic lower intestine (pH 9). Over the entire pH range of the environment the pH of the E. coli cytoplasm is maintained in a narrow range between 7.2 and 7.8. Wilks and Slonczewski (Journal of Bacteriology, 189, 2007) used a fluorescent dye to follow the recovery of cytoplasmic pH after an acid shock comparable to what occurs in the human stomach. They found that the pH within the cell recovered in approximately 2 minutes.

Rapid restoration of cytoplasmic pH does not occur in the presence of ATPase inhibitors. Explain for the mechanisms that maintain homeostasis with a model of exchange of hydrogen ions (H⁺) between the cell and its extracellular environment.

We need an explanation of the common experience that an "upset stomach" (functional dyspepsia) or constipation can result from stress. Irritable bowel syndrome is a chronic gastrointestinal disease and is treated with the neurotransmitter serotonin. Serotonin receptors are located on the cell membranes of neurons and activate second messenger cascades that regulate gene expression.

1. In humans most serotonin is synthesized in neurons that enervate smooth muscle cells lining the gastrointestinal tract. There is an association of serotonin with a sense of well-being.
   Based on these data, justify the claim that timing of the passage of food in the gastrointestinal tract is regulated by serotonin.
    
2. The effect of serotonin on smooth muscle is a clue but it doesn't provide a mechanism connecting stress to the symptoms of functional dyspepsia. Serotonin is synthesized by all Bilateria (animals with bilateral symmetry, including humans) and is released as a response to stress (Puglisi-Allegra and Andolini, Behavioral Brain Research, 277, 2015). Serotonin is also synthesized by plants to regulate root growth. Describe the role for serotonin that is indicated across domains.
3. Evaluate the effect that stress produces in serotonin production, the association of stress with functional dyspepsia, and the role of serotonin in the regulation of expression in smooth muscle cells in terms of evidence of a negative feedback produced by serotonin as a medication.
4. Justify your evaluation of the stress and the role of serotonin as a response to the stress in the form of a feedback loop diagrammatically.
5. Quorum sensing coordinates bacterial expression, stimulating virulence factors, and behavior, inducing the formation of biofilms. Knecht et al (EBioMedicine, 9, 2016) have demonstrated that serotonin functions as a quorum sensing messenger among bacteria in the gastrointestinal tract of mice.
   
   Construct an explanation of the effect of serotonin as a treatment of functional dyspepsia.