**Core Concept:** Pseudomembranous colitis (PMC) is a complication of Clostridium difficile (C. difficile) infection, which is a common cause of antibiotic-associated diarrhea. C. difficile produces toxins that damage the intestinal mucosa, leading to inflammation and formation of pseudomembranes (false membranes) in the colon.

**Why the Correct Answer is Right:** The correct answer is **D:** **Fecal Calprotectin**.

Calprotectin is a protein released by neutrophils and monocytes in response to tissue inflammation. In the context of PMC, the elevated fecal calprotectin levels indicate active inflammation and tissue damage, which can be used as a non-invasive marker to diagnose and monitor the disease progression.

**Why Each Wrong Option is Incorrect:**

A. **C. difficile culture (C. difficile culture)**: This investigation is not specific for PMC diagnosis as it requires invasive procedures and is not sensitive enough to detect active inflammation.

B. **C. difficile antigen detection (C. difficile antigen test)**: This test also requires invasive procedures and may not detect active inflammation, as it only detects the presence of C. difficile toxin, not inflammation.

C. **Barium enema**: This investigation is an imaging test, not a direct marker of inflammation or tissue damage, and is not commonly used in the diagnosis of PMC.

**Clinical Pearl:** In PMC, fecal calprotectin is a non-invasive, accurate, and reliable marker for assessing intestinal inflammation and disease activity. It aids in diagnosing PMC, monitoring treatment response, and predicting relapse.