**Core Concept**
Celiac sprue, also known as celiac disease, is an autoimmune disorder characterized by an abnormal immune response to gluten, a protein found in wheat, barley, and rye. This condition leads to chronic inflammation and damage in the small intestine, impairing nutrient absorption.

**Why the Correct Answer is Right**
The correct answer involves the pathophysiology of celiac sprue. Gluten, a protein composed of gliadin and glutenin, triggers an immune response in genetically predisposed individuals. The immune system produces antibodies against tissue transglutaminase (tTG), an enzyme present in the small intestine. This reaction leads to inflammation, villous atrophy, and crypt hyperplasia, ultimately compromising the absorptive surface of the small intestine.

**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because celiac sprue is not primarily caused by a bacterial overgrowth, but rather an autoimmune response to gluten.
**Option B:** This option is incorrect because the primary mechanism of celiac sprue is not related to the release of histamine, but rather an immune response to gluten.
**Option C:** This option is incorrect because the primary location of the immune response in celiac sprue is the small intestine, not the colon.

**Clinical Pearl / High-Yield Fact**
Celiac sprue should be considered in patients with unexplained diarrhea, weight loss, or iron-deficiency anemia, especially in those with a family history of the disease. A gluten-free diet is the primary treatment, leading to significant improvement in symptoms and histological findings.

**Correct Answer:** D.