Intestinal secretory mechanisms and diarrhea

Abstract

One of the primary functions of the intestinal epithelium is to transport fluid and electrolytes to and from the luminal contents. Under normal circumstances, absorptive and secretory processes are tightly regulated such that absorption predominates, thereby enabling conservation of the large volumes of water that pass through the intestine each day. However, in conditions of secretory diarrhea, this balance becomes dysregulated, so that fluid secretion, driven primarily by Cl- secretion, overwhelms absorptive capacity, leading to increased loss of water in the stool. Secretory diarrheas are common and include those induced by pathogenic bacteria and viruses, allergens, and disruptions to bile acid homeostasis, or as a side effect of many drugs. Here, we review the cellular and molecular mechanisms by which Cl- and fluid secretion in the intestine are regulated, how these mechanisms become dysregulated in conditions of secretory diarrhea, currently-available and emerging therapeutic approaches, and how new strategies to exploit intestinal secretory mechanisms are successfully being employed in the treatment of constipation.

Multi-omics profiles of the intestinal microbiome in irritable bowel syndrome and its bowel habit subtypes

“…IBS-D was characterized by increased cholate and isoursodeoxycholate, which is consistent with prior studies reporting increased levels of cholate in IBS-D compared to IBS-C and bile acid malabsorption in IBS-D [ 14 , 16 ]. Bile acids are known to induce diarrhea by triggering colonic chloride secretion, supporting direct involvement in the bowel habit phenotype of IBS-D [ 67 ]. Besides these bile acid shifts, IBS-D was characterized by upregulation of multiple metabolic pathways for bacterial energy harvest including transcripts involved in fructose, mannose, and polyol metabolism.…”

Antihypertensives and Antibiotics: Impact on Intestinal Dysfunction and Hypertension

“…A host of transcellular transport mechanisms regulate intestinal uptake of nutrients and electrolytes. 7 Both the NHE3 (sodium hydrogen exchanger 3) and ENaC (epithelial sodium channel) are highly expressed in the intestine and are responsible for sodium absorption. Thus, breakdown of tight junctions leading to increased permeability and disturbance of gut epithelial transporters may impact chronic disease states, including hypertension.…”

Cross‐talk between zinc and calcium regulates ion transport: A role for the zinc receptor, ZnR/GPR39

“…Transport of Cl − plays an important role in maintaining cell volume. In the digestive system, Cl − absorption is essential for regulation of cell volume and for the electrolyte balance that supports water absorption; indeed, loss of Cl − is closely associated with diarrhoea (Keely & Barrett, 2022). In neurons, the Cl − gradient supports GABA A ‐dependent inhibitory function and is therefore essential for maintaining inhibitory–excitatory balance (Hamze et al., 2021; Kahle et al., 2015).…”

“…Zinc supplementation is recommended by the World Health Organization as an effective method to treat diarrhoea (Lamberti et al., 2013; Lazzerini & Wanzira, 2016; Li et al., 2022). Water loss in diarrhoea is accompanied by loss of Na + and Cl − into the lumen (Keely & Barrett, 2022; Singh et al., 2014). Activation of ZnR/GPR39 by Zn 2+ in colonocytes enhanced transport activity mediated by both NHE and KCC1 and can therefore play a major role in diarrheal diseases.…”