Basic Molecular Biology, Metabolic and Immunological Mechanisms of Fecal Microbiota Transplantation

Aim:  demonstration of basic molecular biological, metabolic and immunological effects of fecal microbiota transplantation (FMT), on the example of a rare case of acute graft-versus-host disease (GVHD) with intestinal damage in a patient after allogeneic hematopoietic stem cell transplantation (allo...

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Main Authors: O. V. Goloshchapov, A. V. Beynarovich, A. B. Chukhlovin, R. V. Klementeva, A. A. Shcherbakov, E. A. Bakin, I. K. Golubovskaya, N. D. Ventslovayte, O. S. Yudintseva, M. V. Gorchakova, V. E. Karev, M. A. Kucher, M. A. Suvorova, E. V. Svetkina, G. G. Rodionov, V. V. Gostev, S. V. Sidorenko, I. S. Moiseev, A. D. Kulagin
Format: Article
Language:Russian
Published: Gastro LLC 2024-12-01
Series:Российский журнал гастроэнтерологии, гепатологии, колопроктологии
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Online Access:https://www.gastro-j.ru/jour/article/view/1117
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author O. V. Goloshchapov
A. V. Beynarovich
A. B. Chukhlovin
R. V. Klementeva
A. A. Shcherbakov
E. A. Bakin
I. K. Golubovskaya
N. D. Ventslovayte
O. S. Yudintseva
M. V. Gorchakova
V. E. Karev
M. A. Kucher
M. A. Suvorova
E. V. Svetkina
G. G. Rodionov
V. V. Gostev
S. V. Sidorenko
I. S. Moiseev
A. D. Kulagin
author_facet O. V. Goloshchapov
A. V. Beynarovich
A. B. Chukhlovin
R. V. Klementeva
A. A. Shcherbakov
E. A. Bakin
I. K. Golubovskaya
N. D. Ventslovayte
O. S. Yudintseva
M. V. Gorchakova
V. E. Karev
M. A. Kucher
M. A. Suvorova
E. V. Svetkina
G. G. Rodionov
V. V. Gostev
S. V. Sidorenko
I. S. Moiseev
A. D. Kulagin
author_sort O. V. Goloshchapov
collection DOAJ
description Aim:  demonstration of basic molecular biological, metabolic and immunological effects of fecal microbiota transplantation (FMT), on the example of a rare case of acute graft-versus-host disease (GVHD) with intestinal damage in a patient after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Materials and methods. To monitor the basic effects of FMT, we performed targeted DNA sequencing of 16S rRNA gene (V3–V4) using MiSeq platform as well as multiplex real-time PCR, MS/gas chromatography technique, immunophenotyping of blood lymphocytes, histological and immunohistochemical techniques.Clinical case. A 40-year-old female patient diagnosed with myelodysplastic syndrome, with a history of two unsuccessful allo-HSCTs due to graft failure, underwent the third haploidentical HSCT (haplo-HSCT) from her father as ‘salvage’ therapy. Due to early viral/bacterial colitis post-transplant associated with a multidrug-resistant strain of K. pneumoniae and herpes virus type 6, FMT was performed on days 46 and 47 after allo-HSCT. Complete resolution of the enteropathy symptoms was noted following FMT. However, immunosuppressive therapy was canceled on D+106 after haplo-HSCT due to the detection of minimal residual disease causing development of the ‘overlap’-type GVHD with damage skin lesions grade 4, and intestinal mucous membranes grade 3. This complication required resumption and subsequent intensification of immunosuppressive therapy with complete resolution of GVHD symptoms. Following FMT treatment, the patient showed complete resolution of clinical colitis symptoms. According to results of 16S rRNA sequencing, the species-specific diversity of fecal microbiota increased significantly, along with decreased relative contents of opportunistic bacteria (Klebsiella, Enterococcus, Streptococcus genera). A significant growth was revealed for commensal Bacteroidota, and re-emergence of Faecalibacterium, Blautia, Roseburia. Acute gastrointestinal GVHD promoted by tacrolimus withdrawal was associated with repeated depletion of intestinal microbiota. Upon resolution of GVHD and resumed immunosuppression, increased microbiota diversity (Shannon index) was again recorded, and the parameters of patient’s fecal microbiota reached the donor values. The microbiota shifts at all clinical stages (before and after FMT, at the peak of acute intestinal GVHD and intensive immunosuppressive therapy) showed some relations with metabolism of bile and fatty acids in blood plasma and immune parameters.Conclusions. FMT may be a component of complex therapy aimed at early reconstitution of immune system and organic acid metabolism in patients after allo-HSCT. The composition of fecal microbiota, metabolic profile and spectrum of lymphocyte subpopulations may be markers for monitoring complex rehabilitation after allo-HSCT.
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spelling doaj-art-c3f879f80451460e93203cac10db553a2025-02-10T16:14:40ZrusGastro LLCРоссийский журнал гастроэнтерологии, гепатологии, колопроктологии1382-43762658-66732024-12-01345597410.22416/1382-4376-2024-34-5-59-741090Basic Molecular Biology, Metabolic and Immunological Mechanisms of Fecal Microbiota TransplantationO. V. Goloshchapov0A. V. Beynarovich1A. B. Chukhlovin2R. V. Klementeva3A. A. Shcherbakov4E. A. Bakin5I. K. Golubovskaya6N. D. Ventslovayte7O. S. Yudintseva8M. V. Gorchakova9V. E. Karev10M. A. Kucher11M. A. Suvorova12E. V. Svetkina13G. G. Rodionov14V. V. Gostev15S. V. Sidorenko16I. S. Moiseev17A. D. Kulagin18R. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov First Saint Petersburg State Medical UniversityR. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov First Saint Petersburg State Medical UniversityR. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov First Saint Petersburg State Medical UniversityR. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov First Saint Petersburg State Medical UniversityR. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov First Saint Petersburg State Medical UniversityR. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov First Saint Petersburg State Medical UniversityR. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov First Saint Petersburg State Medical UniversityPediatric Research and Clinical Center for Infectious Diseases under the Federal Medical Biological AgencyR. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov First Saint Petersburg State Medical UniversityR. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov First Saint Petersburg State Medical UniversityPediatric Research and Clinical Center for Infectious Diseases under the Federal Medical Biological AgencyR. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov First Saint Petersburg State Medical UniversityExplana Research LaboratoryА.М. Nikiforov Russian Center of Emergency and Radiation Medicine of the Ministry of Russian Federation for Civil Defense, Emergencies and Elimination of Consequences of Natural DisastersА.М. Nikiforov Russian Center of Emergency and Radiation Medicine of the Ministry of Russian Federation for Civil Defense, Emergencies and Elimination of Consequences of Natural DisastersPediatric Research and Clinical Center for Infectious Diseases under the Federal Medical Biological Agency; North-Western State Medical University named after I.I. MechnikovPediatric Research and Clinical Center for Infectious Diseases under the Federal Medical Biological Agency; North-Western State Medical University named after I.I. MechnikovR. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov First Saint Petersburg State Medical UniversityR. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov First Saint Petersburg State Medical UniversityAim:  demonstration of basic molecular biological, metabolic and immunological effects of fecal microbiota transplantation (FMT), on the example of a rare case of acute graft-versus-host disease (GVHD) with intestinal damage in a patient after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Materials and methods. To monitor the basic effects of FMT, we performed targeted DNA sequencing of 16S rRNA gene (V3–V4) using MiSeq platform as well as multiplex real-time PCR, MS/gas chromatography technique, immunophenotyping of blood lymphocytes, histological and immunohistochemical techniques.Clinical case. A 40-year-old female patient diagnosed with myelodysplastic syndrome, with a history of two unsuccessful allo-HSCTs due to graft failure, underwent the third haploidentical HSCT (haplo-HSCT) from her father as ‘salvage’ therapy. Due to early viral/bacterial colitis post-transplant associated with a multidrug-resistant strain of K. pneumoniae and herpes virus type 6, FMT was performed on days 46 and 47 after allo-HSCT. Complete resolution of the enteropathy symptoms was noted following FMT. However, immunosuppressive therapy was canceled on D+106 after haplo-HSCT due to the detection of minimal residual disease causing development of the ‘overlap’-type GVHD with damage skin lesions grade 4, and intestinal mucous membranes grade 3. This complication required resumption and subsequent intensification of immunosuppressive therapy with complete resolution of GVHD symptoms. Following FMT treatment, the patient showed complete resolution of clinical colitis symptoms. According to results of 16S rRNA sequencing, the species-specific diversity of fecal microbiota increased significantly, along with decreased relative contents of opportunistic bacteria (Klebsiella, Enterococcus, Streptococcus genera). A significant growth was revealed for commensal Bacteroidota, and re-emergence of Faecalibacterium, Blautia, Roseburia. Acute gastrointestinal GVHD promoted by tacrolimus withdrawal was associated with repeated depletion of intestinal microbiota. Upon resolution of GVHD and resumed immunosuppression, increased microbiota diversity (Shannon index) was again recorded, and the parameters of patient’s fecal microbiota reached the donor values. The microbiota shifts at all clinical stages (before and after FMT, at the peak of acute intestinal GVHD and intensive immunosuppressive therapy) showed some relations with metabolism of bile and fatty acids in blood plasma and immune parameters.Conclusions. FMT may be a component of complex therapy aimed at early reconstitution of immune system and organic acid metabolism in patients after allo-HSCT. The composition of fecal microbiota, metabolic profile and spectrum of lymphocyte subpopulations may be markers for monitoring complex rehabilitation after allo-HSCT.https://www.gastro-j.ru/jour/article/view/1117fecal microbiota transplantationgraft-versus-host diseaseallogeneic hematopoietic stem cell transplantationmetabolomebile acidslymphocyte subpopulation
spellingShingle O. V. Goloshchapov
A. V. Beynarovich
A. B. Chukhlovin
R. V. Klementeva
A. A. Shcherbakov
E. A. Bakin
I. K. Golubovskaya
N. D. Ventslovayte
O. S. Yudintseva
M. V. Gorchakova
V. E. Karev
M. A. Kucher
M. A. Suvorova
E. V. Svetkina
G. G. Rodionov
V. V. Gostev
S. V. Sidorenko
I. S. Moiseev
A. D. Kulagin
Basic Molecular Biology, Metabolic and Immunological Mechanisms of Fecal Microbiota Transplantation
Российский журнал гастроэнтерологии, гепатологии, колопроктологии
fecal microbiota transplantation
graft-versus-host disease
allogeneic hematopoietic stem cell transplantation
metabolome
bile acids
lymphocyte subpopulation
title Basic Molecular Biology, Metabolic and Immunological Mechanisms of Fecal Microbiota Transplantation
title_full Basic Molecular Biology, Metabolic and Immunological Mechanisms of Fecal Microbiota Transplantation
title_fullStr Basic Molecular Biology, Metabolic and Immunological Mechanisms of Fecal Microbiota Transplantation
title_full_unstemmed Basic Molecular Biology, Metabolic and Immunological Mechanisms of Fecal Microbiota Transplantation
title_short Basic Molecular Biology, Metabolic and Immunological Mechanisms of Fecal Microbiota Transplantation
title_sort basic molecular biology metabolic and immunological mechanisms of fecal microbiota transplantation
topic fecal microbiota transplantation
graft-versus-host disease
allogeneic hematopoietic stem cell transplantation
metabolome
bile acids
lymphocyte subpopulation
url https://www.gastro-j.ru/jour/article/view/1117
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