Iberoamerican Journal of Medicine
https://app.periodikos.com.br/journal/iberoamericanjm/article/doi/10.53986/ibjm.2022.0010
Iberoamerican Journal of Medicine
Original article

Alterations of gut bacteria Akkermansia muciniphila and Faecalibacterium prausnitzii in late post-transplant period after liver transplantation

Alteraciones de las bacterias intestinales Akkermansia muciniphila y Faecalibacterium prausnitzii en el postrasplante tardío tras trasplante hepático

Alexander Kukov, Milena Peruhova, Atanas Syarov, Iskra Altankova, Nonka Yurukova, Andrei Goncharov, Radoslava Vazharova, Anoaneta Mihova, Tsvetelina Velikova, Yordanka Uzunova

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Abstract

Introduction: Recent studies have shown that the intestinal microbiota can modulate certain systemic metabolic and immune responses, including liver graft function and the development of complications in patients after liver transplantation (LT). Akkermansia muciniphila (AKM) and Faecalibacterium prausnitzii (FAEP) are two of the most abundant gut commensal bacteria, with mucosa-protective and anti-inflammatory effects that are important for maintaining normal intestinal homeostasis and gut barrier function. Our objective was to quantify levels of Akkermansia muciniphila and Faecalibacterium prausnitzii in immunosuppressed patients with LT.
Materials and methods: Fecal samples from 23 liver transplant patients (15 adults and 8 children) and 9 non-LT controls were examined. Bacterial DNA was isolated from the samples using the stool DNA isolation kit and the obtained DNA was analyzed with commercially available qPCR kit for AKM and FAEP.
Results: We found a statistically significant decrease in the amount of AKM and FAEP compared to the control group. The median values were: for AKM 8.75 for patients and 10.25 for the control group (p = 0.030), and for FAEP 9.72 and 10.47, p = 0.003, respectively. In children after LT, this difference was also statistically significant: AKM (p = 0.051) and FAEP (p = 0.014). In contrast no statistically significant differences were found between adult patients and controls, AKM (p = 0.283) and FAEP (p = 0.056), although the amount of both bacteria showed tendency for reduction.
Conclusions: In this pilot study, we found a reduction in the total amount of the two studied bacteria in transplanted patients compared to the control healthy group.

Keywords

Akkermansia muciniphila; Faecalibacterium prausnitzii; Gut microbiota; Liver transplantation; Immunosuppression

Resumen

Introducción: Estudios recientes han demostrado que la microbiota intestinal puede modular determinadas respuestas metabólicas e inmunitarias sistémicas, entre ellas la función del injerto hepático y el desarrollo de complicaciones en pacientes tras un trasplante hepático (TH). Akkermansia muciniphila (AKM) y Faecalibacterium prausnitzii (FAEP) son dos de las bacterias comensales intestinales más abundantes, con efectos protectores de la mucosa y antiinflamatorios que son importantes para mantener la homeostasis intestinal normal y la función de barrera intestinal. Nuestro objetivo fue cuantificar los niveles de Akkermansia muciniphila y Faecalibacterium prausnitzii en pacientes inmunodeprimidos con TH.
Materiales y métodos: Se examinaron muestras fecales de 23 pacientes trasplantados de hígado (15 adultos y 8 niños) y 9 controles sin TH. El ADN bacteriano se aisló de las muestras utilizando el kit de aislamiento de ADN de heces y el ADN obtenido se analizó con el kit qPCR disponible comercialmente para AKM y FAEP.
Resultados: Encontramos una disminución estadísticamente significativa en la cantidad de AKM y FAEP en comparación con el grupo control. Los valores medianos fueron: para AKM 8,75 para los pacientes y 10,25 para el grupo control (p = 0,030), y para FAEP 9,72 y 10,47, p = 0,003, respectivamente. En niños tras TH, esta diferencia también fue estadísticamente significativa: AKM (p = 0,051) y FAEP (p = 0,014). Por el contrario, no se encontraron diferencias estadísticamente significativas entre pacientes adultos y controles, AKM (p = 0,283) y FAEP (p = 0,056), aunque la cantidad de ambas bacterias mostró tendencia a la reducción.
Conclusiones: En este estudio piloto, encontramos una reducción en la cantidad total de las dos bacterias estudiadas en pacientes trasplantados en comparación con el grupo control sano.

Palabras clave

Akkermansia muciniphila; Faecalibacterium prausnitzii; Microbiota intestinal; Trasplante de hígado; Inmunosupresión

References

1. Kriss M, Verna EC, Rosen HR, Lozupone CA. Functional Microbiomics in Liver Transplantation: Identifying Novel Targets for Improving Allograft Outcomes. Transplantation. 2019;103(4):668-78. doi: 10.1097/TP.0000000000002568.
2. Tripathi A, Debelius J, Brenner DA, Karin M, Loomba R, Schnabl B, et al. The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol. 2018;15(7):397-411. doi: 10.1038/s41575-018-0011-z.
3. Corrêa-Oliveira R, Fachi JL, Vieira A, Sato FT, Vinolo MA. Regulation of immune cell function by short-chain fatty acids. Clin Transl Immunology. 2016;5(4):e73. doi: 10.1038/cti.2016.17.
4. Fan H, Li LX, Han DD, Kou JT, Li P, He Q. Increase of peripheral Th17 lymphocytes during acute cellular rejection in liver transplant recipients. Hepatobiliary Pancreat Dis Int. 2012;11(6):606-11. doi: 10.1016/s1499-3872(12)60231-8.
5. Grander C, Adolph TE, Wieser V, Lowe P, Wrzosek L, Gyongyosi B, et al. Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease. Gut. 2018;67(5):891-901. doi: 10.1136/gutjnl-2016-313432.
6. Miquel S, Martín R, Rossi O, Bermúdez-Humarán LG, Chatel JM, Sokol H, et al. Faecalibacterium prausnitzii and human intestinal health. Curr Opin Microbiol. 2013;16(3):255-61. doi: 10.1016/j.mib.2013.06.003.
7. Wu ZW, Ling ZX, Lu HF, Zuo J, Sheng JF, Zheng SS, et al. Changes of gut bacteria and immune parameters in liver transplant recipients. Hepatobiliary Pancreat Dis Int. 2012;11(1):40-50. doi: 10.1016/s1499-3872(11)60124-0.
8. Peruhova M, Peshevska-Sekulovska M, Velikova T. Interactions between human microbiome, liver diseases, and immunosuppression after liver transplant. World J Immunol. 2021;11(2):11-6. doi: 10.5411/wji.v11.i2.11.
9. Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489(7415):220-30. doi: 10.1038/nature11550.
10. Gabarre P, Loens C, Tamzali Y, Barrou B, Jaisser F, Tourret J. Immunosuppressive therapy after solid organ transplantation and the gut microbiota: Bidirectional interactions with clinical consequences. Am J Transplant. 2021. doi: 10.1111/ajt.16836.
11. Jiang JW, Ren ZG, Lu HF, Zhang H, Li A, Cui GY, et al. Optimal immunosuppressor induces stable gut microbiota after liver transplantation. World J Gastroenterol. 2018;24(34):3871-83. doi: 10.3748/wjg.v24.i34.3871.
12. Tourret J, Willing BP, Dion S, MacPherson J, Denamur E, Finlay BB. Immunosuppressive Treatment Alters Secretion of Ileal Antimicrobial Peptides and Gut Microbiota, and Favors Subsequent Colonization by Uropathogenic Escherichia coli. Transplantation. 2017;101(1):74-82. doi: 10.1097/TP.0000000000001492.
13. Lopez-Siles M, Enrich-Capó N, Aldeguer X, Sabat-Mir M, Duncan SH, Garcia-Gil LJ, et al. Alterations in the Abundance and Co-occurrence
of Akkermansia muciniphila and Faecalibacterium prausnitzii in the Colonic Mucosa of Inflammatory Bowel Disease Subjects. Front Cell Infect Microbiol. 2018;8:281. doi: 10.3389/fcimb.2018.00281.
14. Martín R, Miquel S, Benevides L, Bridonneau C, Robert V, Hudault S, et al. Functional Characterization of Novel Faecalibacterium prausnitzii Strains Isolated from Healthy Volunteers: A Step Forward in the Use of F. prausnitzii as a Next-Generation Probiotic. Front Microbiol. 2017;8:1226. doi: 10.3389/fmicb.2017.01226.
15. Cani PD, de Vos WM. Next-Generation Beneficial Microbes: The Case of Akkermansia muciniphila. Front Microbiol. 2017;8:1765. doi: 10.3389/fmicb.2017.01765.
16. Tuomisto S, Pessi T, Collin P, Vuento R, Aittoniemi J, Karhunen PJ. Changes in gut bacterial populations and their translocation into liver and ascites in alcoholic liver cirrhotics. BMC Gastroenterol. 2014;14:40. doi: 10.1186/1471-230X-14-40.
17. Bajaj JS, Fagan A, Sikaroodi M, White MB, Sterling RK, Gilles H, et al, Gillevet PM. Liver transplant modulates gut microbial dysbiosis and cognitive function in cirrhosis. Liver Transpl. 2017;23(7):907-14. doi: 10.1002/lt.24754.
18. Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504(7480):446-50. doi: 10.1038/nature12721.
19. Zhou L, Zhang M, Wang Y, Dorfman RG, Liu H, Yu T, et al. Faecalibacterium prausnitzii Produces Butyrate to Maintain Th17/Treg Balance and to Ameliorate Colorectal Colitis by Inhibiting Histone Deacetylase 1. Inflamm Bowel Dis. 2018;24(9):1926-40. doi: 10.1093/ibd/izy182.
20. Satapathy SK, Banerjee P, Pierre JF, Higgins D, Dutta S, Heda R, et al. Characterization of Gut Microbiome in Liver Transplant Recipients With Nonalcoholic Steatohepatitis. Transplant Direct. 2020;6(12):e625. doi: 10.1097/TXD.0000000000001033.
21. Sun LY, Yang YS, Qu W, Zhu ZJ, Wei L, Ye ZS, et al. Gut microbiota of liver transplantation recipients. Sci Rep. 2017;7(1):3762. doi: 10.1038/s41598-017-03476-4.
22. Jiao W, Zhang Z, Xu Y, Gong L, Zhang W, Tang H, et al. Butyric acid normalizes hyperglycemia caused by the tacrolimus-induced gut microbiota. Am J Transplant. 2020;20(9):2413-24. doi: 10.1111/ajt.15880.
23. Guo Y, Crnkovic CM, Won KJ, Yang X, Lee JR, Orjala J, et al. Commensal Gut Bacteria Convert the Immunosuppressant Tacrolimus to Less Potent Metabolites. Drug Metab Dispos. 2019;47(3):194-202. doi: 10.1124/dmd.118.084772.


Submitted date:
11/18/2021

Reviewed date:
12/15/2021

Accepted date:
01/17/2022

Publication date:
01/17/2022

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