Targeted Stem Cell and Peptide-Based Therapeutics for Gut Diseases: Restoring the Stomach and Intestinal Mucosa through Microbiome and Mitochondrial Modulation: Research Article

Mike KS Chan; Michelle BF Wong; Krista Casazza; Waldemar Lerhardt; Eric Mathur; Dmytro Klokol; Ian Jenkins; Jonathan RT Lakey

doi:10.58372/2835-6276.1336

Authors

Mike KS Chan
Michelle BF Wong
Krista Casazza
Waldemar Lerhardt
Eric Mathur
Dmytro Klokol
Ian Jenkins
Jonathan RT Lakey

DOI:

https://doi.org/10.58372/2835-6276.1336

Abstract

Background: The gastrointestinal (GI) tract is one of the most dynamic tissue environments in the body, requiring constant regeneration to preserve mucosal integrity against microbial, dietary, and inflammatory stressors. When repair mechanisms fail, chronic gut diseases such as inflammatory bowel disease (IBD), gastritis, ulcerative colitis, Crohn’s disease, and mucosal injury syndromes emerge. These conditions are increasingly recognized as resulting from the convergence of impaired epithelial regeneration, microbiome dysbiosis, and mitochondrial dysfunction.

Objective: To propose and evaluate an integrative therapeutic paradigm that combines organ-specific progenitor stem cells with next-generation peptide therapeutics, particularly nano-organo peptides (NOPs) and mitochondrial-targeted peptides (MO peptides), for mucosal restoration in chronic GI diseases.

Methods: A synthesis of recent advances in epithelial progenitor biology, peptide engineering, and microbiome–host crosstalk was undertaken. Mechanistic insights were integrated with translational strategies, focusing on the regenerative potential of stem cell–peptide combinations.

Results: Evidence supports that progenitor cell–based therapies enhance epithelial regeneration, while peptide therapeutics, including NOPs and MO peptides, can target organelle dysfunction and restore barrier integrity. Together, these approaches act synergistically to repair mucosa, rebalance microbial ecosystems, and restore mitochondrial health. Early preclinical findings suggest feasibility for precision and regenerative interventions that move beyond symptomatic management.

Conclusions: Restoring the epithelial–microbiome–mitochondrial axis represents a transformative strategy for chronic gut diseases. Integrating progenitor stem cells with engineered peptide therapeutics holds promise to overcome current therapeutic limitations and accelerate translation into clinical practice.

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