Effect of Sublimated Mare Milk Supplement on Gut Microbiome in Psoriasis Patients

Eurasia Invest Ltd., Ministry of Education and Science, Republic of Kazakhstan, Centre for Dermatology and Sexually Transmitted Diseases, Astana, Kazakhstan

This study evaluates the effect of dietary supplement consisting of sublimated mare milk on intestinal microbiota among psoriasis and healthy participants.

The gut microbiome is believed to play an important role in the immune system regulation, since intestines are the largest lymphoid organ in a human body. Deviations from healthy composition of intestinal flora are associated with various diseases including allergy and autoimmunity. Psoriasis is the one of the long-lasting autoimmune diseases that is characterized by patches on the skin and further health complications throughout the life. However, lack of studies does not allow proper evaluation of role of gut microbiome in psoriasis patients. Therefore, potential interplay between gut microbiome and immune system in psoriasis would be studied in this clinical trial. Particularly, the investigators hypothesize that sublimated mare milk supplement can have an impact on gut immune system and gut microbiome composition in the psoriasis patients. In this trial, there will be two parallel groups: crossover psoriasis patients (standard treatment first for 3 months, next 3 months standard treatment plus sublimated mare milk supplement) and healthy volunteers group. Subsequently, association of intestinal flora with immune status will be analyzed and compared between these groups.

Patients with verified diagnosis of psoriasis would be given standard treatment for the first 3 months, and then followed with the standard therapy accompanied with the sublimated mare milk supplement for additional 3 months.

Healthy patients will be enrolled in this study, and their gut microbiota composition as well as immune system indicators will be used for comparison with the psoriasis group.

The dietary supplement mare milk product, which is obtained from fresh (few hours) through sublimation process. This product is first mixed with warm water (37-38 degrees of Celsius) and then will be given to participants.

Change in composition of intestinal microbiota will be determined comparing with the baseline results using DNA sequencing Illumina MiSeq System.

The change of immunity will be evaluated from stool specimens according to baseline results of inflammatory cytokines, interleukins, and antibodies. Number of patients, in whom change is statistically significant, will be reported in the results.

Dermatological status of PASI index will be evaluated according to the international protocols for treatment of psoriasis (NICE guidance).

Inclusion Criteria. Inclusion criteria for experimental group: Patients with a verified diagnosis of moderate to severe psoriasis Aged 30 to 45 years Absence of an allergic reaction to dairy products Lack of prescription of antibacterial drugs for the last 3 months prior to admission Willingness to consent to participate in the study Inclusion criteria for healthy volunteers group. Patients with no diagnosis of psoriasis Aged 30 to 45 years Exclusion Criteria: Presence of chronic dermatoses, diseases of the organs of the gastrointestinal tract Presence of severe concomitant diseases of the kidneys, liver, cardiovascular, respiratory and other body systems, oncological, mental health and decompensated endocrine diseases, tuberculosis, and HIV infection Pregnancy and/or lactation Patient involvement in other clinical trials within the last 3 months Refusal to participate in the study

Fung I, Garrett JP, Shahane A, Kwan M. Do bugs control our fate? The influence of the microbiome on autoimmunity. Curr Allergy Asthma Rep. 2012 Dec;12(6):511-9. doi: 10.1007/s11882-012-0291-2.

Ely PH. Is psoriasis a bowel disease? Successful treatment with bile acids and bioflavonoids suggests it is. Clin Dermatol. 2018 May-Jun;36(3):376-389. doi: 10.1016/j.clindermatol.2018.03.011. Epub 2018 Mar 28.

Yan D, Issa N, Afifi L, Jeon C, Chang HW, Liao W. The Role of the Skin and Gut Microbiome in Psoriatic Disease. Curr Dermatol Rep. 2017 Jun;6(2):94-103. doi: 10.1007/s13671-017-0178-5. Epub 2017 Apr 22.

Scher JU, Ubeda C, Artacho A, Attur M, Isaac S, Reddy SM, Marmon S, Neimann A, Brusca S, Patel T, Manasson J, Pamer EG, Littman DR, Abramson SB. Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis Rheumatol. 2015 Jan;67(1):128-39. doi: 10.1002/art.38892.

Gao Z, Tseng CH, Strober BE, Pei Z, Blaser MJ. Substantial alterations of the cutaneous bacterial biota in psoriatic lesions. PLoS One. 2008 Jul 23;3(7):e2719. doi: 10.1371/journal.pone.0002719.

Codoner FM, Ramirez-Bosca A, Climent E, Carrion-Gutierrez M, Guerrero M, Perez-Orquin JM, Horga de la Parte J, Genoves S, Ramon D, Navarro-Lopez V, Chenoll E. Gut microbial composition in patients with psoriasis. Sci Rep. 2018 Feb 28;8(1):3812. doi: 10.1038/s41598-018-22125-y.

Eppinga H, Sperna Weiland CJ, Thio HB, van der Woude CJ, Nijsten TE, Peppelenbosch MP, Konstantinov SR. Similar Depletion of Protective Faecalibacterium prausnitzii in Psoriasis and Inflammatory Bowel Disease, but not in Hidradenitis Suppurativa. J Crohns Colitis. 2016 Sep;10(9):1067-75. doi: 10.1093/ecco-jcc/jjw070. Epub 2016 Mar 12.

Yegorov S, Babenko D, Kozhakhmetov S, Akhmaltdinova L, Kadyrova I, Nurgozhina A, Nurgaziyev M, Good SV, Hortelano GH, Yermekbayeva B, Kushugulova A. Psoriasis Is Associated With Elevated Gut IL-1alpha and Intestinal Microbiome Alterations. Front Immunol. 2020 Oct 1;11:571319. doi: 10.3389/fimmu.2020.571319. eCollection 2020.

Togzhan Algazina, Alexandr Gulyayev, Alma Aimoldina, Almagul Kushugulova, Bakytgul Yermekbayeva*. Clinical assessment of the use of sublimated mare's milk in complex therapy of mild and moderate psoriasis // Journal of Global Pharma Technology.- 2020.- Vol.12.- Issue 06.- P. 18-25