High Throughput Analysis Reveals Changes in Gut Microbiota and Specific Fecal Metabolomic Signature in Hematopoietic Stem Cell Transplant Patients

Abstract

There is mounting evidence for the emerging role of gut microbiota (GM) and its metabolites in profoundly impacting allogenic hematopoietic stem cell transplantation (allo-HSCT) and its subsequent complications, mainly infections and graft versus host-disease (GvHD). The present study was performed in order to investigate changes in GM composition and fecal metabolic signature between transplant patients (n = 15) and healthy controls (n = 18). The intestinal microbiota was characterized by NGS and gas chromatography–mass spectrometry was employed to perform untargeted analysis of fecal metabolites. We found lower relative abundances of Actinobacteria, Firmicutes, and Bacteroidetes and a higher abundance of Proteobacteria phylum after allo-HSCT. Particularly, the GvHD microbiota was characterized by a lower relative abundance of the short-chain fatty acid-producing bacteria, namely, the Feacalibacterium, Akkermansia, and Veillonella genera and the Lachnospiraceae family, and an enrichment in multidrug-resistant bacteria belonging to Escherichia, Shigella, and Bacteroides. Moreover, network analysis showed that GvHD was linked to a higher number of positive interactions of Blautia and a significant mutual-exclusion rate of Citrobacter. The fecal metabolome was dominated by lipids in the transplant group when compared with the healthy individuals (p < 0.05). Overall, 76 metabolites were significantly altered within transplant recipients, of which 24 were selected as potential biomarkers. Furthermore, the most notable altered metabolic pathways included the TCA cycle; butanoate, propanoate, and pyruvate metabolisms; steroid biosynthesis; and glycolysis/gluconeogenesis. Specific biomarkers and altered metabolic pathways were correlated to GvHD onset. Our results showed significant shifts in gut microbiota structure and fecal metabolites characterizing allo-HSCT.

The distribution of intestinal flora after hematopoietic stem cell transplantation in children

“…The commensal bacteria Ruminococcaceae_UGG_013 , Veillonella , Bacillales , and Bifidobacteriaceae were screened out as possible GI GVHD biomarkers. Among them, Veillonella , Ruminococcus , and Bifidobacteriaceae all can produce SCFAs, which can enhance intestinal defense by improving the integrity of intestinal epithelial cell junctions, thereby reducing local inflammation, improving GVHD, and reducing mortality 7,29,30 . Furthermore, the two genera Veillonella and Hungatella , which had not been reported in GI GVHD before, may be influential in the development of GI GVHD, but their specific effects require further verification.…”

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“…In the treatment of rCDI, the success rates were approached up to 92%. [14] FMT have achieved more success to treat different kinds of ailments so the use of FMT increasing day by day, which growing the demand of fecal material of standard quality.…”

Dynamics of gut microbiota in patients suffering from hematologic malignancies after allogeneic hematopoi-etic stem cell transplantation

“…Количество представителей отдела Firmicutes изменялось незначительно. Данный факт примечателен, так как в исследованиях других научных групп отмечено снижение относительной численности фирмикут после ТГСК [12; 18], а в ряде работ низкая доля этих бактерий ассоциирована с дисбиозом [19]. Представленность отдела Bacteroidetes снижалась в поздний посттрансплантационный период ( р < 0,001), что согласуется с литературными данными [12; 19].…”

“…Доля представителей отдела Actinobacteria уменьшалась в ранний период после ТГСК ( р = 0,019), но возвращалась к исходному уровню уже через 30 дней. В исследовании С. Куиди с соавторами также отмечено снижение доли актинобактерий у реципиентов ТГСК [19]. Количество представителей отдела Proteobacteria варьировалось в широких пределах и статистически значимо не отличалось у пациентов с симптомами РТПХ и без данного осложнения.…”

“…Отсутствие достоверных отличий в доле протеобактерий отмечено и в работе Н. Манцини с соавторами [12]. В ранее упомянутом исследовании С. Куиди с коллегами, напротив, выявлено повышение относительного количества представителей отдела Proteobacteria после ТГСК [19].…”