Methods of treating patients afflicted with irritable bowel syndrome, inflammatory bowel disease or chronic gastrointestinal functional disorders based on assessment of intestinal barrier function

A method of treating a patient afflicted with one or more symptoms of irritable bowel syndrome and inflammatory bowel disease comprising:

• (a) analyzing the status of an intestinal barrier in said patient;
• and
• (b) categorizing the patient's intestinal barrier status as severe dysfunction or mild dysfunction based on the amount of caspase-1 in said patient, and
• (c) treating said patient with a first agent if said patient has mild dysfunction or treating said patient with a second agent if said patient has severe dysfunction;
• wherein status of the intestinal barrier is analyzed by counting a number of extrusion zones or gaps in histological staining of an intestinal surface at the intestinal barrier;
• wherein an increase in the number of extrusion zones or gaps in the range of two fold to four-fold in the patient as compared to a number of extrusion zones or gaps in an intestinal surface at an intestinal barrier of a healthy subject indicates that the patient status is mild dysfunction;
• wherein an increase in the number of extrusion zones or gaps in the range of four-fold to seven-fold in the patient as compared to a number of extrusion zones or gaps in an intestinal surface at an intestinal barrier of a healthy subject indicates that the patient status is severe dysfunction;
• wherein said first agent is selected from a group consisting of an anti-integrin agent, an anti-janus kinase agent, a sphingosine-1-phosphate receptor agonist agent, and a combination of two or more of an anti-integrin agent, an anti-janus kinase agent, and a sphingosine-1-phosphate receptor agonist agent;
• and
• wherein said second agent is selected from a group consisting of an anti-TNF-α agent, an anti-IL-12/23 agent, an anti-IL-12 agent, an anti IL-23 agent, and a combination of an anti-TNF agent, and an anti-IL-12/23 agent.

A method of improving the treatment of a patient with irritable bowel syndrome or inflammatory bowel disease comprising:

• (a) analyzing a status of an intestinal barrier in the patient to obtain a patient intestinal barrier status;
• and
• (b) categorizing the patient intestinal barrier status as severe dysfunction or mild dysfunction, and
• (c) wherein a patient categorized as having severe dysfunction is then treated with an agent that inhibits one or more of TNF-α, IL-12, and IL-23, or
• (d) wherein a patient categorized as having mild dysfunction is then treated with an agent that inhibits one or more of integrin, janus kinase, sphingosine-1-phosphate receptor, or a combination of two or more of integrin, janus kinase, and sphingosine-1-phosphate receptor;
• wherein an increase in the amount of activated caspase-1 in the range of two-fold to four-fold in the patient as compared to a control amount of activated caspase-1, wherein the control is the amount of activated caspase-1 in intestinal epithelial cells of an intestinal barrier of a healthy subject indicates that the patient status is mild dysfunction;
• and
• wherein an increase in the amount of activated caspase-1 in the range of four-fold to seven-fold in the patient as compared to a control amount of activated caspase-1, wherein the control is the amount of activated caspase-1 in intestinal epithelial cells of an intestinal barrier of a healthy subject indicates that the patient status is severe dysfunction.

A method of treating a patient afflicted with one or more symptoms of chronic gastrointestinal functional disorders comprising:

• (a) analyzing the status of an intestinal barrier in said patient;
• and
• (b) categorizing the patient's intestinal barrier status as severe dysfunction or mild dysfunction based on amount of caspase-1 expression, and
• (c) treating said patient having mild dysfunction with an agent that inhibits one or more of integrin, janus kinase, sphingosine-1-phosphate receptor, or a combination of two or more of integrin, janus kinase, and sphingosine-1-phosphate receptor or treating said patient having severe dysfunction with an agent that inhibits one or more of TNF-α, IL-12, and IL-23;
• wherein an increase in the amount of activated caspase-1 expression in the range of two-fold to four-fold in the patient as compared to a control amount of activated caspase-1, wherein the control is the amount of activated caspase-1 in intestinal epithelial cells of an intestinal barrier of a healthy subject indicates that the patient status is mild dysfunction;
• wherein an increase in the amount of activated caspase-1 in the range of four-fold to seven-fold in the patient as compared to a control amount of activated caspase-1, wherein the control is the amount of activated caspase-1 in intestinal epithelial cells of an intestinal barrier of a healthy subject indicates that the patient status is severe dysfunction.