Irritable bowel syndrome with constipation and its treatment

Irritable Bowel Syndrome (IBS) is a digestive functional disorder, which is characterized clinically by the association of swelling, abdominal pain / discomfort and alterations in the depositional habit that can vary from constipation, diarrhea or both.

Linaclotide is approved for the treatment of irritable bowel syndrome with constipation (IBS-C). This drug acts as a receptor agonist for guanylate cyclase C, stimulates the secretion of chlorine and bicarbonate and consequent water entrainment into the gastrointestinal lumen.

Among the mechanisms by which the symptoms of IBS-C appear, alteration of the intestinal microflora was proposed. In the proximal colon metabolizes proteins and carbohydrates in a fermentation process, from which short-chain fatty acids are obtained. Since its quantification is an invasive process, with technical challenges, in many cases the intracolonic pH is evaluated as an indirect marker of bacterial fermentation.

In a recent study evaluating the effect of linaclotide on pH changes in the ileocecal junction (UIC) and its relationship with symptoms and quality of life of patients with IBS-C; Also, the effect on the measurements of motility and regional transit time was evaluated by using a wireless mobility capsule (WMC), a minimally invasive technique, capable of taking measurements of pressure, temperature and pH while traversing the tract. gastrointestinal.

Since the pH gradient decreases at the UIC level, this value could indirectly represent the degree of fermentation that occurs in the proximal portion of the colon.

In this investigation the use of linaclotide was associated with the reduction in the time of colonic transit (2650 versus 1757 minutes, p = 0.02), with the increase in the motility index (15 ± 1.8 vs. 16.5 ± 1.8, p = 0.004). ) and the decrease in stool consistency, intensity, discomfort and anxiety; also, improvements in the quality of life related to health were observed.

The use of linaclotide was related to the decrease in the fermentation process in the cecum, given the reduction observed in the pH change throughout the UIC; it also accelerated the transit time of the colon, with a concomitant increase in the motility index.

As explained by the authors, the changes were correlated with the improvement in stool consistency, spontaneous defecation, intensity and discomfort, but no changes were found in the motility index of the stomach or small intestine, as long as they observed improvements in the quality of life.

The highest concentration of short-chain fatty acids is detected in the cecum and decreases as it progresses to more distal portions of the colon. This observation suggests that the highest degree of fermentation occurs in the right colon. In the patients with IBS, alterations in the colonic fermentation were demonstrated and it was postulated that these seem to contribute in the appearance of symptoms such as abdominal distension.

A randomized double-blind study evaluating the effect of administration of 100 mcg and 1000 mcg of linaclotide against placebo on gastrointestinal transit in 36 patients with IBS-C demonstrated a significant therapeutic effect on emptying of the ascending colon and general colonic transit , but found no effect on gastric emptying or colon filling.

According to the authors, the work carried out was the first to analyze, specifically, the effect of the available dose of the drug studied on the physiology of the gastrointestinal tract with the use of WMC.

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