Matching between Donors and Ulcerative Colitis Patients Is Important for Long-Term Maintenance after Fecal Microbiota Transplantation

Okahara, Koki; Ishikawa, Dai; Nomura, Kei; Ito, Shoko; Haga, Keiichi; Takahashi, Masahito; Shibuya, Tomoyoshi; Osada, Taro; Nagahara, Akihito

doi:10.3390/jcm9061650

Cited by 41 publications

(31 citation statements)

References 51 publications

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“…In our study and previous clinical reports (Okahara et al, 2020), the difference in the resilience of transplanted microbiota was attributed to the age difference between FMT donors and recipients. It is possible that age-matching is not the only factor determining the long-term stability of transplanted microbiota.…”

Section: Discussionsupporting

confidence: 80%

“…However, autologous FMT is not always a clinically available option, especially for aged hosts, and rational donor selection largely determines the patient response (Duvallet et al, 2019; Kassam et al, 2019; Vermeire et al, 2016; Wilson et al, 2019). One study of ulcerative colitis patients reported that long-term post-FMT maintenance was significantly affected by the age difference between donors and patients (Okahara et al, 2020). Another study of FMT for CDI patients found a higher relapse rate among elderly patients compared with younger counterparts during the 6-month period after FMT (Tseng et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Establishment and Resilience of Transplanted Gut Microbiota in Aged Mice

Wang

Tang

et al. 2021

Preprint

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Fecal microbiota transplantation (FMT), a procedure in which fecal material is transferred from a donor to a recipient, has been increasingly used as a treatment to restore healthy gut microbiota. There is a substantial difference in the composition of gut microbiota between young and aged hosts, but little is known about whether age matching between the FMT donor and recipient affects microbiota restoration and long-term maintenance. In the present investigation, we aimed to study the establishment and resilience of transplanted gut microbiota in aged recipients. We treated naturally aged mice (20 months old) with a broad-spectrum antibiotic cocktail and monitored the restoration of gut microbiota over 8 weeks. The diversity of gut microbiota in aged mice failed to reach the baseline level via spontaneous recovery; in contrast, FMT from either (age-)matched or unmatched donors facilitated the recovery of gut microbiota diversity. The microbiota transplanted from different donors successfully established in the aged recipients and had long-term effects on the gene expression profiles of the host colon. Finally, we evaluated the long-term maintenance of transplanted microbiota via intentional disruption of gut homeostasis. We found that lack of age matching between FMT donors and recipients may decrease the resilience of transplanted gut microbiota against colonic inflammation. The results from our study systematically examining the effects of FMT on the gut homeostasis of aged hosts suggest that the compatibility between donors and recipients should be taken into account when implementing FMT.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Establishment and Resilience of Transplanted Gut Microbiota in Aged Mice

Wang

Tang

et al. 2021

Preprint

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“…The healthy controls were donor candidates from the clinical study of FMT. Health of donor candidates was ensured by the Juntendo donor screening criteria [12][13][14]. Donor candidates, who had been exposed to antibiotics within 3 months before the commencement of the study were excluded.…”

Section: Patients and Healthy Controlsmentioning

confidence: 99%

“…Moreover, we found that a single session of FMT following triple-antibiotic therapy (amoxicillin, fosfomycin, and metronidazole) reduced the symptoms of intestinal dysbiosis in patients with UC. This was achieved by the successful transplantation of live Bacteroidetes cells from donors, with both short-term efficacy and long-term maintenance of treatment [12][13][14]. Other reports have also suggested that improvement in the diversity and composition of Bacteroidetes species is beneficial for UC [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Bacteroidetes Species Are Correlated with Disease Activity in Ulcerative Colitis

Nomura

Ishikawa

Okahara

et al. 2021

JCM

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Fecal microbiota transplantation following triple-antibiotic therapy (amoxicillin/fosfomycin/metronidazole) improves dysbiosis caused by reduced Bacteroidetes diversity in patients with ulcerative colitis (UC). We investigated the correlation between Bacteroidetes species abundance and UC activity. Fecal samples from 34 healthy controls and 52 patients with active UC (Lichtiger’s clinical activity index ≥5 or Mayo endoscopic subscore ≥1) were subjected to next-generation sequencing with HSP60 as a target in bacterial metagenome analysis. A multiplex gene expression assay using colonoscopy-harvested mucosal tissues determined the involvement of Bacteroidetes species in the mucosal immune response. In patients with UC, six Bacteroides species exhibited significantly lower relative abundance, and twelve Bacteroidetes species were found significantly correlated with at least one metric of disease activity. The abundance of five Bacteroidetes species (Alistipes putredinis, Bacteroides stercoris, Bacteroides uniformis, Bacteroides rodentium, and Parabacteroides merdae) was correlated with three metrics, and their cumulative relative abundance was strongly correlated with the sum of Mayo endoscopic subscore (R = −0.71, p = 2 × 10−9). Five genes (TARP, C10ORF54, ITGAE, TNFSF9, and LCN2) associated with UC pathogenesis were expressed by the 12 key species. The loss of key species may exacerbate UC activity, serving as potential biomarkers.

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“…FMT may contribute towards disease remission in UC, but the factors determine long-term effect of treatment is not completely clear. Matching between donors and UC patients is important for long-term maintenance after FMT [ 42 ]. Sustained remission was associated with known butyrate producers and overall increased butyrate production capacity, while relapse was associated with Proteobacteria and Bacteroidetes [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Long-term efficacy and safety of monotherapy with a single fresh fecal microbiota transplant for recurrent active ulcerative colitis: a prospective randomized pilot study

Hou

Lian

et al. 2021

Microb Cell Fact

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Background To assess the long-term safety and efficacy of monotherapy with a single fresh fecal microbiota transplant (FMT) for recurrent ulcerative colitis (UC). Results Twenty-six eligible patients were enrolled, and 6 patients were excluded. Ultimately, 20 patients were randomized to the FMT group (n = 10) and the control group (n = 10); 80% were females (F/M = 16/4), the mean age was 48 ± 14 years, and the mean duration was 6.4 ± 8.2 years. The mean length of post-FMT follow-up was 19.1 ± 10.1 months (6–38). No statistically significant differences in baseline demographic or clinical characteristics were found between the groups. Ninety percent of patients in the FMT group and 50% of patients in the control group met the primary endpoint at week 8. The Mayo score was significantly decreased compared with that of the control group (n = 10) when reassessed at week 4 (P = 0.001) and week 8 (P = 0.019) after FMT; there was no significant difference 6 months after treatment. The median remission time was 24 months (95% CI 68.26–131.7%) in both the FMT (range 6–38 months) and control groups (range 7–35 months), with no significant difference (P = 0.895). Participants tolerated FMT treatment, and no adverse events occurred during long-term follow-up, with one treatment-related significant adverse event (EBV infection) occurring within 2 weeks after FMT. Stool microbiota composition analysis indicated improved gut microbiota diversity after FMT, with expansion of stool-donor taxa. Bacteroidetes, Firmicutes and Proteobacteria were the dominant bacterial phyla of the gut microbiota in active UC patients. The relative abundance of Bacteroidetes decreased and that of Proteobacteria increased significantly in active UC patients compared with donors, while Firmicutes showed no significant changes. A single fresh FMT could effectively reconstruct the gut microbiota composition in patients with active UC and maintain stability, with increased Bacteroidetes and decreased Proteobacteria abundance. FMT significantly reduced the relative abundance of Escherichia and increased the relative abundance of Prevotella at the genus level. Pyruvate metabolism, glyoxylate and dicarboxylate metabolism, and pantothenate and CoA biosynthesis showed significant differences after transplantation. Conclusions Monotherapy with a single fresh FMT is an effective and safe strategy to induce long-term remission without drugs in patients with active UC and may be an alternative induction therapy for recurrent UC or even primary UC.

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Matching between Donors and Ulcerative Colitis Patients Is Important for Long-Term Maintenance after Fecal Microbiota Transplantation

Cited by 41 publications

References 51 publications

Establishment and Resilience of Transplanted Gut Microbiota in Aged Mice

Establishment and Resilience of Transplanted Gut Microbiota in Aged Mice

Bacteroidetes Species Are Correlated with Disease Activity in Ulcerative Colitis

Long-term efficacy and safety of monotherapy with a single fresh fecal microbiota transplant for recurrent active ulcerative colitis: a prospective randomized pilot study

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