Citation: Iatrou, A.M.; Michailidou, S.; Papadopoulos, G.A.; Afaloniati, H.; Lagou, M.K.; Kiritsi, M.; Argiriou, A.; Angelopoulou, K.; Poutahidis, T.; Fortomaris, P. Effects of Dietary Supplementation of Spirulina platensis on the Immune System, Intestinal Bacterial Microbiome and Skin Traits of Mink. Animals 2023, 13, 190. https://doi.org/10.3390/ ani13020190 Academic Editor: Federico Infascelli Received: 9 December 2022 Revised: 29 December 2022 Accepted: 30 December 2022 Published: 4 January 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). animals Article Effects of Dietary Supplementation of Spirulina platensis on the Immune System, Intestinal Bacterial Microbiome and Skin Traits of Mink Anna Maria Iatrou 1, * , Sofia Michailidou 2 , Georgios A. Papadopoulos 1 , Hara Afaloniati 3 , Maria K. Lagou 4 , Maria Kiritsi 2 , Anagnostis Argiriou 2,5 , Katerina Angelopoulou 3 , Theofilos Poutahidis 4 and Paschalis Fortomaris 1 1 Laboratory of Animal Husbandry, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece 2 Center for Research and Technology, Hellas Institute of Applied Biosciences, Thermi, 57001 Thessaloniki, Greece 3 Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece 4 Laboratory of Pathology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece 5 Department of Food Science and Nutrition, University of the Aegean, 81400 Lemnos, Greece * Correspondence: ipannama@vet.auth.gr; Tel.: +30-2310999958 Simple Summary: Many dietary practices have been previously applied in mink farming to improve the health and productivity of the animals. Spirulina platensis (Spirulina), a natural feed supplement, has demonstrated beneficial effects on the health and productivity of various animal species. To the best of our knowledge, the effect of Spirulina supplementation on the health of mink has not been previously studied. To address this dearth of knowledge, we investigated the effects of Spirulina supplementation on the immune system, gut bacterial microbiome and skin of mink. Spirulina decreased the markers of subclinical inflammation of the mink gastrointestinal system. Moreover, differences in the bacterial communities’ compositions among groups were observed. Dietary inclusion of Spirulina at a dose of 100 mg/kg of body weight did not affect either the growth of animals or the skin and pelt quality. Overall, it can be suggested that Spirulina can be used with mink to promote their intestinal health and immune status. However, further studies may be required to investigate the effect of other levels of Spirulina dietary supplementation. Abstract: The impact of dietary inclusion of Spirulina platensis on the immune system, intestinal microbiome and skin of mink was investigated. Forty-eight animals were equally separated into four groups. Groups B and D were control animals, while groups A and C had their feed supplemented daily with 100 mg/kg of body weight Spirulina. Mink in groups A and B were descended from dams supplemented with spirulina during their reproductive period, while those in groups C and D were descended from dams fed the control diets. Fur growth rate and quality were graded semi- quantitatively. Fecal microbiome analysis, skin thickness histomorphometry, immunohistochemical labeling and counts of immune cells in the colon, mesenteric lymph nodes and spleen and quantitative gene expression analysis of cytokines in the colon were performed. Skin thickness, fur growth rate and skin quality were similar among groups (p > 0.05). However, differences were observed among groups concerning the relative and differential abundance of bacterial species. Tgf-β expression was lower in group A, whereas IL-β1 was lower in group C compared to group B (p < 0.05). Group D had significantly lower numbers of inflammatory cells in the colon and mesenteric lymph nodes. The results revealed that Spirulina decreased indices of subclinical inflammation in mink gut, while differences in the bacterial communities among groups were observed. Keywords: Spirulina; mink; gut; microbiome; immune system; skin quality Animals 2023, 13, 190. https://doi.org/10.3390/ani13020190 https://www.mdpi.com/journal/animals