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Abstract

Helicobacter pylori is a highly prevalent gastric pathogen (colonizing ∼50% of people worldwide) that causes chronic gastritis, peptic ulcer disease, MALT lymphoma, and gastric cancer. Rising antibiotic resistance (e.g. >15% clarithromycin resistance) has compromised standard eradication regimens, necessitating novel therapies. SH-HP (His-D-Trp-Ala-Trp-D-Phe-Lys) is a synthetic hexapeptide analogue of the endogenous hormone ghrelin/GHRP-6, originally developed as a growth hormone secretagogue. Preclinical studies reveal that SH-HP/GHRP-6 has potent gastroprotective and anti-inflammatory effects: it prevents stress-induced gastric mucosal lesions and mitigates multiorgan damage in ischemia/reperfusion models. Given that ghrelin receptor signaling plays a key role in gut mucosal defense (via nitric oxide and prostaglandins) and gut–brain homeostasis, we hypothesize that SH-HP may improve outcomes in H. pylori infection and acute gastric injury. This paper reviews the background and rationale for SH-HP therapy, including its effects on mucosal integrity, systemic inflammation, and the gut–brain axis. We propose a randomized, placebo-controlled clinical trial (see Table 1) to evaluate SH-HP as an adjunct to standard H. pylori eradication therapy. If effective, SH-HP could represent a new adjunctive treatment to protect the gastric mucosa, counteract inflammation, and restore neuroendocrine balance in infected patients.

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