Can proton pump inhibitors be used to treat protein‑induced colitis, and are they appropriate only when there is a separate acid‑related indication?

PPI Use in Protein-Induced Colitis

Proton pump inhibitors have no role in the treatment of protein-induced colitis and should only be prescribed when a separate, valid acid-related indication exists (such as gastroesophageal reflux disease or peptic ulcer disease). 1

Why PPIs Are Not Indicated for Protein-Induced Colitis

Protein-induced colitis is a non-IgE-mediated food allergy, most commonly triggered by cow's milk or soy protein in infants, that causes colonic inflammation through immune mechanisms unrelated to gastric acid secretion. 1 The pathophysiology involves T-cell mediated hypersensitivity reactions in the colonic mucosa, not acid-related mucosal injury. 1

The cornerstone of treatment for protein-induced colitis is elimination of the offending protein antigen from the diet—either through maternal dietary restriction during breastfeeding or switching to an extensively hydrolyzed or amino acid-based formula. 1 PPIs do not address this underlying mechanism and provide no therapeutic benefit for the colitis itself.

When PPIs May Be Appropriate in These Patients

PPIs should only be used in infants or children with protein-induced colitis if they have a concurrent, documented acid-related condition that warrants acid suppression independently, such as:

• Gastroesophageal reflux disease (GERD) with esophagitis or significant symptoms that persist despite conservative measures 2
• Peptic ulcer disease (rare in this age group) 2
• Other validated acid-related indications 1

In pediatric GERD specifically, PPIs are indicated when there is documented erosive esophagitis or when symptoms significantly impair quality of life despite lifestyle modifications and thickened feeds. 2 The diagnosis should be confirmed rather than empirically treating suspected reflux, as PPI overprescription in pediatrics is a significant concern. 2

Important Caveats About PPI Use in Colitis

Emerging evidence suggests PPIs may actually worsen inflammatory bowel conditions through several mechanisms:

• Gut microbiota disruption: PPIs reduce microbial diversity and promote dysbiosis, which can exacerbate intestinal inflammation 3, 4
• Increased intestinal permeability: Long-term PPI use disrupts tight junction barriers via myosin light chain kinase activation, increasing gut permeability 4
• Association with microscopic colitis: PPIs are a recognized trigger for microscopic colitis (both collagenous and lymphocytic subtypes), and discontinuation should be considered when this diagnosis is made 1, 5, 6
• Worse IBD outcomes: In inflammatory bowel disease patients, PPI use correlates with increased hospitalizations, need for biologics, and disease flares 7, 6

While protein-induced colitis differs mechanistically from IBD, the principle that PPIs can promote intestinal inflammation through microbiome alterations and barrier dysfunction suggests they should be avoided unless clearly necessary. 1, 3, 4

Clinical Algorithm

For an infant/child with protein-induced colitis:

1. Eliminate the offending protein (cow's milk, soy) through maternal diet restriction or appropriate formula change 1
2. Assess for separate GERD symptoms (frequent regurgitation, feeding refusal, arching, failure to thrive) 2
3. If GERD symptoms are present:
   • First try conservative measures: smaller, more frequent feeds; upright positioning after feeds; thickened feeds if appropriate 2
   • Consider endoscopy if symptoms persist to document esophagitis before starting PPI 2
   • Only initiate PPI if documented esophagitis or severe symptoms unresponsive to conservative measures 2, 1
4. If no acid-related symptoms exist, do not prescribe PPI 1
5. If already on PPI without clear indication, discontinue it to avoid potential worsening of intestinal inflammation 1, 5

Monitoring Considerations

If a PPI must be used for a valid concurrent indication:

• Use the lowest effective dose and shortest duration necessary 1
• Reassess necessity regularly and attempt discontinuation when the acid-related condition resolves 1
• Monitor for worsening colitis symptoms (increased bloody stools, diarrhea) that might indicate PPI-related intestinal barrier dysfunction 4
• Be aware that fecal calprotectin may be elevated by PPI use itself, independent of disease activity, requiring a 3-week washout before using this marker to assess colitis 1