Exploring the Gut–Skin Microbiome and Leishmaniasis: A Systematic Review of Current Evidence
-
Azadeh Zolfaghari
,
Sarah Seyedyousefi
,
Parisa Mousavi
,
Zabihollah Shahmoradi
,
Hanieh Sharifian
,
Maryam Aghaei
,
Seyedmohsen Hosseini
Abstract
Background: This review investigated the impact of skin and gut microbiomes on the development of leishmaniasis. Dysbiosis in these microbiomes is associated with various skin disorders through mechanisms related to immune modulation and inflammation. Leishmaniasis primarily presents as cutaneous wounds. The immune response of the host to Leishmania plays a crucial role in determining the disease's severity and treatment effectiveness. Gaining insight into these microbiome-immune dynamics is essential for improving the prevention and management of leishmaniasis.
Methods: A thorough analysis of the most recent research was done, emphasizing the functions of chemokines and cytokines in Leishmania infection. Synthesizing key findings from research indexed by PubMed, Scopus, Web of Science, Science Direct, EMBASE, and Magiran up to June 2024 provided an extensive understanding of immunological mechanisms. Eventually, 19 manuscripts were included in this review and thoroughly investigated and reported.
Results: The delicate balance between pro- and anti-inflammatory signals in the immune response to Leishmania infection largely depends on the commensal microbial populations.
Conclusion: Future research should concentrate on modifying these reactions to improve treatment outcomes for leishmaniasis.
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2. Zhang X-E, Zheng P, Ye S-Z, et al. Microbiome: Role in Inflammatory Skin Diseases. J Inflamm Res. 2024;17:1057-1082.
3. De Pessemier B, Grine L, Debaere M, et al. Gut-Skin Axis: Current Knowledge of the Interrelationship between Microbial Dysbiosis and Skin Conditions. Microorganisms. 2021;9(2):353.
4. Wang L, Xu Y-N, Chu C-C, et al. Facial Skin Microbiota-Mediated Host Response to Pollution Stress Revealed by Microbiome Networks of Individual. mSystems. 2021;6(4): e0031921.
5. Liang D, Leung RK, Guan W, et al. Involvement of gut microbiome in human health and disease: brief overview, knowledge gaps and research opportunities. Gut Pathog. 2018;10:3.
6. Arck P, Handjiski B, Hagen E, et al. Is there a 'gut-brain-skin axis'? Exp Dermatol. 2010;19(5):401–5.
7. Savoia D, Scutera S, Raimondo S, et al. Activity of an engineered synthetic killer peptide on Leishmania major and Leishmania infantum promastigotes. Exp Parasitol .2006;113(3):186–92.
8. Sabzevari S, Teshnizi SH, Shokri A, et al. Cutaneous leishmaniasis in Iran: A systematic review and meta-analysis. Microb Pathog. 2021;152:104721.
9. Zolfaghari A, Beheshti-Maal K, Ahadi AM, et al. Identification of Leishmania species and frequency distribution of LRV1 and LRV2 viruses on cutaneous leishmaniasis patients in Isfahan Province, Iran. Indian J Med Microbiol. 2023;41:13–18.
10. Mousavi P, Rahimi Esboei B, Pourhajibagher M, et al. Anti-leishmanial effects of resveratrol and resveratrol nanoemulsion on Leishmania major. BMC Microbiol. 2022;22(1):56.
11. Abtahi-Naeini B, Hadian S, Sokhanvari F, , et al. Effect of Adjunctive Topical Liposomal Azithromycin on Systemic Azithromycin on Old World Cutaneous Leishmaniasis: A Pilot Clinical Study. Iran J Pharm Res. 2021;20(2):383–9.
12. Elmahallawy EK, Alkhaldi AAM, Saleh AA. Host immune response against leishmaniasis and parasite persistence strategies: A review and assessment of recent research. Biomed Pharmacother. 2021;139:111671.
13. Farias Amorim C, Lovins VM, Singh TP, et al. Multiomic profiling of cutaneous leishmaniasis infections reveals microbiota-driven mechanisms underlying disease severity. Sci Transl Med. 2023;15(718):eadh1469.
14. Gunathilaka N, Siriwardana T, Erathna S, et al. Microbial diversity in cutaneous leishmaniasis lesions and potential implications for disease progression and treatment outcomes. BMC Res Notes. 2025;18(1):351.
15. Higgins JPT, Morgan RL, Rooney AA, et al. A tool to assess risk of bias in non-randomized follow-up studies of exposure effects (ROBINS-E). Environ Int. 2024;186:108602.
16. de Oliveira MR, Tafuri WL, Nicoli JR, et al. Influence of microbiota in experimental cutaneous leishmaniasis in Swiss mice. Rev Inst Med Trop Sao Paulo. 1999;41(2):87–94.
17. Julia V, McSorley SS, Malherbe L, et al. Priming by microbial antigens from the intestinal flora determines the ability of CD4+ T cells to rapidly secrete IL-4 in BALB/c mice infected with Leishmania major. J Immunol. 2000;165(10):5637–45.
18. Lamour SD, Veselkov KA, Posma JM, et al. Metabolic, immune, and gut microbial signals mount a systems response to Leishmania major infection. J Proteome Res. 2015;14(1):318–29.
19. Lewis MD, Paun A, Romano A, et al. Fatal progression of experimental visceral leishmaniasis is associated with intestinal parasitism and secondary infection by commensal bacteria, and is delayed by antibiotic prophylaxis. PLoS Pathog. 2020;16(4):e1008456.
20. Lopes ME, Dos Santos LM, Sacks D, et al. Resistance Against Leishmania major Infection Depends on Microbiota-Guided Macrophage Activation. Front Immunol. 2021;12:730437.
21. Mrázek J, Mrázková L, Mekadim C, et al. Effects of Leishmania major infection on the gut microbiome of resistant and susceptible mice. Appl Microbiol Biotechnol. 2024;108(1):145.
22. Naik S, Bouladoux N, Wilhelm C, et al. Compartmentalized control of skin immunity by resident commensals. Science. 2012;337(6098):1115–9.
23. Oliveira MR, Tafuri WL, Afonso LC, et al. Germ-free mice produce high levels of interferon-gamma in response to infection with Leishmania major but fail to heal lesions. Parasitology. 2005;131(Pt 4):477–88.
24. Singh TP, Carvalho AM, Sacramento LA, et al. Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis. PLoS Pathog. 2021;17(10):e1009693.
25. Jaimes J, Patiño LH, Herrera G, et al. Prokaryotic and eukaryotic skin microbiota modifications triggered by Leishmania infection in localized Cutaneous leishmaniasis. PLoS Negl Trop Dis. 2024;18(3):e0012029.
26. Kaluarachchi TDJ, Campbell PM, Wickremasinghe R, et al. Possible clinical implications and future directions of managing bacterial biofilms in cutaneous leishmaniasis wounds. Trop Med Health. 2022;50(1):58.
27. Lappan R, Classon C, Kumar S, et al. Meta-taxonomic analysis of prokaryotic and eukaryotic gut flora in stool samples from visceral leishmaniasis cases and endemic controls in Bihar State India. PLoS Negl Trop Dis. 2019;13(9):e0007444.
28. Olías-Molero AI, Botías P, Cuquerella M, et al. Leishmania infantum infection does not affect the main composition of the intestinal microbiome of the Syrian hamster. Parasit Vectors. 2022;15(1):468.
29. Passos FC, Gois MB, Sousa AD, et al. Investigating associations between intestinal alterations and parasite load according to Bifidobacterium spp. and Lactobacillus spp. abundance in the gut microbiota of hamsters infected by Leishmania infantum. Mem Inst Oswaldo Cruz. 2020;115:e200377.
30. Gimblet C, Meisel JS, Loesche MA, et al. Cutaneous Leishmaniasis Induces a Transmissible Dysbiotic Skin Microbiota that Promotes Skin Inflammation. Cell Host Microbe. 2017;22(1):13–24.e4.
31. Singh TP, Farias Amorim C, Lovins VM, et al. Regulatory T cells control Staphylococcus aureus and disease severity of cutaneous leishmaniasis. J Exp Med. 2023;220(12): e20230558.
32. Meazzi S, Lauzi S, Martini V, et al. Gut Microbiota and Lymphocyte Subsets in Canine Leishmaniasis. Front Vet Sci. 2022;9:868967.
33. Fontes CO, Carvalho MAR, Nicoli JR, et al. Identification and antimicrobial susceptibil-ity of micro-organisms recovered from cutaneous lesions of human American tegumentary leishmaniasis in Minas Gerais, Brazil. J Med Microbiol. 2005;54(Pt 11):1071–6.
34. Sadeghian G, Ziaei H, Bidabadi LS, et al. Decreased effect of glucantime in cutaneous leishmaniasis complicated with secondary bacterial infection. Indian J Dermatol. 2011;56(1):37–9.
35. Sadeghian G Sb, Ziaei H, Hejazi Sh, et al. Evaluation of glucantime activity in cutaneous leishmaniasis lesions contamina-ted with secondary bacterial infection compared with non infected lesions. Annals Mil Health Res. 2010;8:6-10.
36. Vieira LQ, Oliveira MR, Neumann E, et al. Parasitic infections in germ free animals. Braz J Med Biol Res. 1998;31(1):105–10.
37. Ribeiro-Gomes FL, Sacks D. The influence of early neutrophil-Leishmania interactions on the host immune response to infection. Front Cell Infect Microbiol. 2012;2:59.
38. Chaves MM, Lee SH, Kamenyeva O, et al. The role of dermis resident macrophages and their interaction with neutrophils in the early establishment of Leishmania major infection transmitted by sand fly bite. PLoS Pathog. 2020; 16(11):e1008674.
39. Saini A, Dalal P, Sharma D. Deciphering the interdependent labyrinth between gut microbiota and the immune system. Lett Appl Microbiol. 2022;75(5):1122–35.
40. Khavkin AI, Sitkin SI. The effect of targeted probiotics on the microbiota–gut–immune system axis. Voprosy Praktičeskoj Pediatrii. 2023: 18(6):107-118.
41. Hassani-Abharian P, Ghanadian M, Fassihi A, et al. Profiling fungal secondary metabolites with anti-leishmanial activity: an integrated in silico and in vitro study. Sci Rep. 2026; doi: 10.1038/s41598-026-59741-y.
42. Kogut MH, Lee A, Santin E. Microbiome and pathogen interaction with the immune system. Poult Sci. 2020;99(4):1906–13.
43. Mazziotta C, Tognon M, Martini F, et al. Probiotics Mechanism of Action on Immune Cells and Beneficial Effects on Human Health. Cells. 2023;12(1):184.
44. Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography. Nature. 2012; 486(7402):222–7.
45. Jayasena Kaluarachchi TD, Campbell PM, Wickremasinghe R, et al. Distinct microbiome profiles and biofilms in Leishmania donovani-driven cutaneous leishmaniasis wounds. Sci Rep. 2021;11(1):23181.
2. Zhang X-E, Zheng P, Ye S-Z, et al. Microbiome: Role in Inflammatory Skin Diseases. J Inflamm Res. 2024;17:1057-1082.
3. De Pessemier B, Grine L, Debaere M, et al. Gut-Skin Axis: Current Knowledge of the Interrelationship between Microbial Dysbiosis and Skin Conditions. Microorganisms. 2021;9(2):353.
4. Wang L, Xu Y-N, Chu C-C, et al. Facial Skin Microbiota-Mediated Host Response to Pollution Stress Revealed by Microbiome Networks of Individual. mSystems. 2021;6(4): e0031921.
5. Liang D, Leung RK, Guan W, et al. Involvement of gut microbiome in human health and disease: brief overview, knowledge gaps and research opportunities. Gut Pathog. 2018;10:3.
6. Arck P, Handjiski B, Hagen E, et al. Is there a 'gut-brain-skin axis'? Exp Dermatol. 2010;19(5):401–5.
7. Savoia D, Scutera S, Raimondo S, et al. Activity of an engineered synthetic killer peptide on Leishmania major and Leishmania infantum promastigotes. Exp Parasitol .2006;113(3):186–92.
8. Sabzevari S, Teshnizi SH, Shokri A, et al. Cutaneous leishmaniasis in Iran: A systematic review and meta-analysis. Microb Pathog. 2021;152:104721.
9. Zolfaghari A, Beheshti-Maal K, Ahadi AM, et al. Identification of Leishmania species and frequency distribution of LRV1 and LRV2 viruses on cutaneous leishmaniasis patients in Isfahan Province, Iran. Indian J Med Microbiol. 2023;41:13–18.
10. Mousavi P, Rahimi Esboei B, Pourhajibagher M, et al. Anti-leishmanial effects of resveratrol and resveratrol nanoemulsion on Leishmania major. BMC Microbiol. 2022;22(1):56.
11. Abtahi-Naeini B, Hadian S, Sokhanvari F, , et al. Effect of Adjunctive Topical Liposomal Azithromycin on Systemic Azithromycin on Old World Cutaneous Leishmaniasis: A Pilot Clinical Study. Iran J Pharm Res. 2021;20(2):383–9.
12. Elmahallawy EK, Alkhaldi AAM, Saleh AA. Host immune response against leishmaniasis and parasite persistence strategies: A review and assessment of recent research. Biomed Pharmacother. 2021;139:111671.
13. Farias Amorim C, Lovins VM, Singh TP, et al. Multiomic profiling of cutaneous leishmaniasis infections reveals microbiota-driven mechanisms underlying disease severity. Sci Transl Med. 2023;15(718):eadh1469.
14. Gunathilaka N, Siriwardana T, Erathna S, et al. Microbial diversity in cutaneous leishmaniasis lesions and potential implications for disease progression and treatment outcomes. BMC Res Notes. 2025;18(1):351.
15. Higgins JPT, Morgan RL, Rooney AA, et al. A tool to assess risk of bias in non-randomized follow-up studies of exposure effects (ROBINS-E). Environ Int. 2024;186:108602.
16. de Oliveira MR, Tafuri WL, Nicoli JR, et al. Influence of microbiota in experimental cutaneous leishmaniasis in Swiss mice. Rev Inst Med Trop Sao Paulo. 1999;41(2):87–94.
17. Julia V, McSorley SS, Malherbe L, et al. Priming by microbial antigens from the intestinal flora determines the ability of CD4+ T cells to rapidly secrete IL-4 in BALB/c mice infected with Leishmania major. J Immunol. 2000;165(10):5637–45.
18. Lamour SD, Veselkov KA, Posma JM, et al. Metabolic, immune, and gut microbial signals mount a systems response to Leishmania major infection. J Proteome Res. 2015;14(1):318–29.
19. Lewis MD, Paun A, Romano A, et al. Fatal progression of experimental visceral leishmaniasis is associated with intestinal parasitism and secondary infection by commensal bacteria, and is delayed by antibiotic prophylaxis. PLoS Pathog. 2020;16(4):e1008456.
20. Lopes ME, Dos Santos LM, Sacks D, et al. Resistance Against Leishmania major Infection Depends on Microbiota-Guided Macrophage Activation. Front Immunol. 2021;12:730437.
21. Mrázek J, Mrázková L, Mekadim C, et al. Effects of Leishmania major infection on the gut microbiome of resistant and susceptible mice. Appl Microbiol Biotechnol. 2024;108(1):145.
22. Naik S, Bouladoux N, Wilhelm C, et al. Compartmentalized control of skin immunity by resident commensals. Science. 2012;337(6098):1115–9.
23. Oliveira MR, Tafuri WL, Afonso LC, et al. Germ-free mice produce high levels of interferon-gamma in response to infection with Leishmania major but fail to heal lesions. Parasitology. 2005;131(Pt 4):477–88.
24. Singh TP, Carvalho AM, Sacramento LA, et al. Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis. PLoS Pathog. 2021;17(10):e1009693.
25. Jaimes J, Patiño LH, Herrera G, et al. Prokaryotic and eukaryotic skin microbiota modifications triggered by Leishmania infection in localized Cutaneous leishmaniasis. PLoS Negl Trop Dis. 2024;18(3):e0012029.
26. Kaluarachchi TDJ, Campbell PM, Wickremasinghe R, et al. Possible clinical implications and future directions of managing bacterial biofilms in cutaneous leishmaniasis wounds. Trop Med Health. 2022;50(1):58.
27. Lappan R, Classon C, Kumar S, et al. Meta-taxonomic analysis of prokaryotic and eukaryotic gut flora in stool samples from visceral leishmaniasis cases and endemic controls in Bihar State India. PLoS Negl Trop Dis. 2019;13(9):e0007444.
28. Olías-Molero AI, Botías P, Cuquerella M, et al. Leishmania infantum infection does not affect the main composition of the intestinal microbiome of the Syrian hamster. Parasit Vectors. 2022;15(1):468.
29. Passos FC, Gois MB, Sousa AD, et al. Investigating associations between intestinal alterations and parasite load according to Bifidobacterium spp. and Lactobacillus spp. abundance in the gut microbiota of hamsters infected by Leishmania infantum. Mem Inst Oswaldo Cruz. 2020;115:e200377.
30. Gimblet C, Meisel JS, Loesche MA, et al. Cutaneous Leishmaniasis Induces a Transmissible Dysbiotic Skin Microbiota that Promotes Skin Inflammation. Cell Host Microbe. 2017;22(1):13–24.e4.
31. Singh TP, Farias Amorim C, Lovins VM, et al. Regulatory T cells control Staphylococcus aureus and disease severity of cutaneous leishmaniasis. J Exp Med. 2023;220(12): e20230558.
32. Meazzi S, Lauzi S, Martini V, et al. Gut Microbiota and Lymphocyte Subsets in Canine Leishmaniasis. Front Vet Sci. 2022;9:868967.
33. Fontes CO, Carvalho MAR, Nicoli JR, et al. Identification and antimicrobial susceptibil-ity of micro-organisms recovered from cutaneous lesions of human American tegumentary leishmaniasis in Minas Gerais, Brazil. J Med Microbiol. 2005;54(Pt 11):1071–6.
34. Sadeghian G, Ziaei H, Bidabadi LS, et al. Decreased effect of glucantime in cutaneous leishmaniasis complicated with secondary bacterial infection. Indian J Dermatol. 2011;56(1):37–9.
35. Sadeghian G Sb, Ziaei H, Hejazi Sh, et al. Evaluation of glucantime activity in cutaneous leishmaniasis lesions contamina-ted with secondary bacterial infection compared with non infected lesions. Annals Mil Health Res. 2010;8:6-10.
36. Vieira LQ, Oliveira MR, Neumann E, et al. Parasitic infections in germ free animals. Braz J Med Biol Res. 1998;31(1):105–10.
37. Ribeiro-Gomes FL, Sacks D. The influence of early neutrophil-Leishmania interactions on the host immune response to infection. Front Cell Infect Microbiol. 2012;2:59.
38. Chaves MM, Lee SH, Kamenyeva O, et al. The role of dermis resident macrophages and their interaction with neutrophils in the early establishment of Leishmania major infection transmitted by sand fly bite. PLoS Pathog. 2020; 16(11):e1008674.
39. Saini A, Dalal P, Sharma D. Deciphering the interdependent labyrinth between gut microbiota and the immune system. Lett Appl Microbiol. 2022;75(5):1122–35.
40. Khavkin AI, Sitkin SI. The effect of targeted probiotics on the microbiota–gut–immune system axis. Voprosy Praktičeskoj Pediatrii. 2023: 18(6):107-118.
41. Hassani-Abharian P, Ghanadian M, Fassihi A, et al. Profiling fungal secondary metabolites with anti-leishmanial activity: an integrated in silico and in vitro study. Sci Rep. 2026; doi: 10.1038/s41598-026-59741-y.
42. Kogut MH, Lee A, Santin E. Microbiome and pathogen interaction with the immune system. Poult Sci. 2020;99(4):1906–13.
43. Mazziotta C, Tognon M, Martini F, et al. Probiotics Mechanism of Action on Immune Cells and Beneficial Effects on Human Health. Cells. 2023;12(1):184.
44. Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography. Nature. 2012; 486(7402):222–7.
45. Jayasena Kaluarachchi TD, Campbell PM, Wickremasinghe R, et al. Distinct microbiome profiles and biofilms in Leishmania donovani-driven cutaneous leishmaniasis wounds. Sci Rep. 2021;11(1):23181.
| Files | ||
| Issue | Vol 21 No 3 (2026) | |
| Section | Review Article(s) | |
| Keywords | ||
| Leishmaniasis Gut microbiota Skin microbiota Microflora | ||
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How to Cite
1.
Zolfaghari A, Seyedyousefi S, Mousavi P, Shahmoradi Z, Sharifian H, Aghaei M, Hosseini S. Exploring the Gut–Skin Microbiome and Leishmaniasis: A Systematic Review of Current Evidence. Iran J Parasitol. 2026;21(3):310-325.
