Development of Drugs That Aid To Regain Lost Nutritional Benefit from Food Digestion to Enhance Treatment of Short Bowel Syndrome

 

Short bowel syndrome is a complex disease that affects people who have had a lot of their small intestine removed. The group of problems is characterized by the inability of body to absorb enough nutrients from the foods that is consumed. The condition is also more prevalent in people with small intestine that has been significantly damaged. The condition can be classified as mild, moderate, or severe, depending on the capability of the small intestine to keep functioning. Parenteral support is a widely used treatment options for patients with short bowel syndrome. In parenteral support, patients receive intravenous nutrients, hydration or electrolytes instead of by mouth.

 

The physiologic course of short bowel syndrome is divided into the following phases: acute phase and adaptation phase. In acute phase, high intestinal fluid loss and the metabolic derangement is observed. In adaptation phase, structural and functional changes are observed in remaining small bowel and colon. The condition can be prevalent in people suffering from cancer, Crohn's disease, gastroschisis, internal hernia, intestinal atresia, intestinal injury, trauma, intussusception, meconium ileus, midgut volvulus, and omphalocele. Diarrhea, dehydration, foul-smelling stool, bloating, too much gas, vomiting, cramping, fatigue, heartburn, and weakness are some of the symptoms of the disease. Diagnosis of the condition includes, blood tests, stool exam, X-rays, CT scan, ultrasound, bone density test, and liver biopsy.

The main treatment for short bowel syndrome is nutritional support, which may include oral rehydration, parenteral nutrition, enteral nutrition, and vitamin and mineral supplements. Several therapies used in the treatment of the condition include, antibiotics, H2 blockers, proton pump inhibitors, choleretic agents, bile-salt binders, anti-secretin agents, hypomotility agents, growth hormones, and teduglutide.

The use of various therapies depends upon several factors such as symptoms and the site and extent of the affected portion of the small intestine. The involvement of colon also impacts the treatment. Other factors that impact the use of various therapies include, age, and overall health, tolerance of certain medications or procedures, and personal preferences. Targeted therapy plays a major role in treatment of short bowel syndrome as the therapies are complex and varied. Targeted therapy may include, total parenteral nutrition, enteral feeding, dietary adjustments, oral rehydration solutions, certain medications and/or surgery. Other treatments include, pain management, ostomy, and bowel rehabilitation and transplant.

The U.S. Food and Drug Administration (FDA) has approved both growth hormone and glutamine as drugs to be used in the management of short bowel syndrome. Teduglutide is a 33-membered polypeptide and glucagon-like peptide-2 analog. It promotes mucosal growth and restores gastric emptying and secretion. Although, parenteral support is a widely used treatment options for patients with short bowel syndrome, the process is extremely burdensome. Development of drugs that can help regain lost nutritional benefit from food digestion can be beneficial for people born with an abnormally short digestive tract, or had to have bowel surgically shortened. In this regard, injectable glucagon-like peptide-1 (GLP-1) agonist has demonstrated significant potential. The agonist leverages gut motility effects in patients with short bowel syndrome in order to slow digestive transit time.