ISSN 1866-8836
Клеточная терапия и трансплантация

PC-03. Transplantation of maternal oral microbiota to a child for the prevention of mucositis: a clinical case

Oleg V. Goloshchapov1, Alexey B. Chukhlovin1, Dmitrii S. Bug2, Dmitriy E. Polev3, Oleg V. Kosarev4, Ruslana V. Klementeva1, Ekaterina A. Izmailova1, Ilya V. Kazantsev1, Margarita S. Khalipskaia1, Мaria О. Goloshchapova1, Olesya S. Yudintseva1, Ildar M. Barkhatov1, Natalia V. Petukhova2, Ludmila S. Zubarovskaya1, Alexander D. Kulagin1, Ivan S. Moiseev1

1 RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia
2 Bioinformatics Research Center, Pavlov University, St. Petersburg, Russia
3 St. Petersburg Pasteur Institute, St. Petersburg, Russia
4 St. Petersburg Mining University, St. Petersburg, Russia


Contact: Dr. Oleg V. Goloshchapov, phone: +7 (921) 979-29-13, e-mail: golocht@yandex.ru

doi 10.18620/ctt-1866-8836-2023-12-3-1-176

Summary

Our aim was to test feasibility, safety and efficiency of oral microbiota transplantation (OMT) from a healthy donor to the patient with neuroblastoma in order to prevent oral and intestinal mucositis after cytostatic therapy.

Clinical case

We present a clinical case of a female patient aged 6 months with retroperitoneal neuroblastoma, stage IV (INSS), stage M (INRGSS) with metastatic affection of lungs, bone marrow multiple bone affection), MYCNamp+ del1p- chromosomal aberration. At the clinics of R. Gorbacheva Memorial Institute, the patient underwent therapy by the NB 2004 protocol for the high-risk group, including 6 courses of chemotherapy followed by surgical treatment, autologous hematopoietic stem cell transplantation (auto-HSCT), radiation and targeted immune therapy. Due to development of oral and intestinal mucositis after 3 blocks of chemotherapy accompanied by severe pain and dyspeptic syndrome and infection associated with C.difficile, the oral maternal microbiota transplantation has been decided for this case.

Materials and methods

During the ongoing courses of chemotherapy (blocks 4th to 6th), high-dose-conditioning with auto-HSCT, the patient was subjected to multiple peroral administration of donor oral fluid (mixed, unsimulated). The patient’s mother was used as a saliva donor. To follow the oral microbiota changes, we used target sequencing of 16S rRNA gene (V3-V4 segment). Prior to OMT and at later terms, we studied the samples from the mucobuccal fold, oral fluid, and faeces of donor and recipient. Mucositis severity was documented on daily basis according to WHO criteria. Clinical evaluation was made by the standard international criteria (CTCAE-5).

Results

The signs of oral mucositis were not registered during the three consecutive blocks of chemotherapy. Grade I mucositis was revealed at the myeloablative conditioning regimen before auto-HSCT. The symptoms of intestinal mucositis were not diagnosed. Testing for clostridial antigens A and B showed negative results 5 days after starting the OMT procedure. According to the 16S rRNA gene sequencing, the bacterial microbiota of buccal mucosa, tongue and saliva in the patient exhibited lower contents of conditionally pathogenic bacteria from Staphylococcaceae family (from 30, 47 and 10%, to 0% respectively). The ratio of Micrococcaceae did also show a decrease (from 8, 40, and 50% до 1, 6, and 3%, respectively), along with growing ratio of Streptococcaceae family (from 11%, 1%, 7% to 87%, 38%, 51%, respectively). Our findings after OMT demonstrate some similarities to the donor microbiota pattern observed in all sites of the patient’s microbiota.

Conclusion

A daily multiple transfer of donor oral fluid to the oral cavity of the patient aiming for the mucositis prophylaxis under chemotherapy and conditioning prior to auto-HSCT was associated with sufficient changes in oral microbiota. Any adverse effects and complications were not registered. The results obtained with a single case suggest a need for further studies of the OMT procedure in order to prevent postcytostatic mucositis of gastrointestinal tract.

This study was supported by a research grant from Russian Science Foundation No. №22-15-00149 of 18.05.2022.

Keywords

Oral microbiota, saliva transfer, oral microbiota transplantation, mucositis treatment.


Supplement 12-3
09/30/2023

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doi 10.18620/ctt-1866-8836-2023-12-3-1-176

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