The Ghrelin Analog GHRP-6, Delivered Through Aquafeeds, Modulates the Endocrine and Immune Responses of <i>Sparus aurata</i> Following IFA Treatment.
This study investigated whether dietary supplementation with GHRP-6, a synthetic ghrelin analog peptide, could modulate endocrine and immune responses in gilthead seabream (Sparus aurata), a commercially important aquaculture species. Fish were fed diets containing GHRP-6 for 97 days and then challenged with Incomplete Freund's Adjuvant (IFA), an immune stimulant, via intraperitoneal injection. Samples were collected 72 hours post-injection. The study found that GHRP-6-fed fish maintained more stable plasma levels of lactate, triglycerides, and cortisol following IFA challenge compared to control fish, suggesting reduced metabolic stress. Circulating immunoglobulin levels were significantly elevated in the GHRP-6/IFA group, indicating enhanced humoral immunity. Transcriptomic analysis showed the anterior intestine was the most responsive tissue, with upregulation of immune-related genes including il10, il15, il34, and mx1. Spleen tissue showed increased expression of il8, il10, and ighm, suggesting a balanced inflammatory response. No histological damage was observed in the intestine or spleen. Limitations include the exclusive use of a single fish species, no mammalian or human data, a single GHRP-6 dietary concentration tested, and the authors themselves characterize results as "preliminary."
Why this grade: All experimental work was conducted exclusively in Sparus aurata (gilthead seabream), with no human or mammalian data; findings cannot be directly extrapolated to human health.
The aquaculture industry has experienced considerable growth in recent decades, stimulating research into sustainable and functional feed formulations, mainly related to using high-quality, safe, and environmentally friendly feed ingredients. The employment of immunomodulatory additives is a promising strategy to enhance fish health and performance. In this study, the effects of the ghrelin analog GHRP-6 peptide included in the diet (500 µg/kg of feed) on the endocrine and immune responses of Sparus aurata following Incomplete Freund's adjuvant (IFA) treatment were assessed. After 97 days, fish were intraperitoneally injected with 100 µL of saline solution or IFA/100 g fish and sampled 72 h post-injection. Our results indicated that fish fed GHRP-6 maintained stable plasma levels of lactate, triglycerides, and cortisol after IFA treatment, in contrast to control-fed fish, which showed significant metabolic stress. Circulating immunoglobulin levels enhanced significantly in the GHRP-6/IFA group, suggesting a stimulated humoral immune response. Transcriptomics analysis revealed that the anterior intestine was the most responsive tissue, with upregulation of il10 , il15 , il34 , and mx1 , indicating mucosal immune activation. In the spleen, GHRP-6-fed fish increased il8 , il10 , and ighm expression, highlighting a balanced pro- and anti-inflammatory response and support for adaptive immunity. Multivariate analysis confirmed that dietary GHRP-6 modulates immune gene expression in a tissue- and stimulus-specific manner, without inducing histological alterations in the intestine or spleen. Taken together, these preliminary results indicate that this peptide is a viable and safe dietary supplement to improve immune resilience and increase the production efficiency of S. aurata and suggest a protective effect on the fish's immune system in this species.
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