One dog’s waste is another dog’s wealth: A pilot study of fecal microbiota transplantation in dogs with acute hemorrhagic diarrhea syndrome

Canine acute hemorrhagic diarrhea syndrome (AHDS) has been associated in some studies with Clostridioides perfringens overgrowth and toxin-mediated necrosis of the intestinal mucosa. We aimed to determine the effect of a single fecal microbiota transplantation (FMT) on clinical scores and fecal microbiomes of 1 and 7 dogs with AHDS from New Zealand and South Africa. We hypothesized that FMT would improve AHDS clinical scores and increase microbiota alpha-diversity and short-chain fatty acid (SCFA)-producing microbial communities’ abundances in dogs with AHDS after FMT. We sequenced the V3-V4 region of the 16S-rRNA gene in the feces of AHDS FMT-recipients and sham-treated control dogs, and their healthy donors at admission, discharge, and 30 days post-discharge. There were no significant differences in median AHDS clinical scores between FMT-recipients and sham-treated controls at admission or discharge (P = 0.22, P = 0.41). At admission, the Shannon diversity index (SDI) was lower in AHDS dogs than healthy donors (P = 0.002). The SDI did not change from admission to 30 days in sham-treated dogs yet increased in FMT-recipients from admission to discharge (P = 0.04) to levels not different than donors (P = 0.33) but significantly higher than sham-treated controls (P = 0.002). At 30 days, the SDI did not differ between FMT recipients, sham-treated controls, and donors (P = 0.88). Principal coordinate analysis of the Bray-Curtis index separated post-FMT and donor dogs from pre-FMT and sham-treated dogs (P = 0.009) because of increased SCFA-producing genera’s abundances after FMT. A single co-abundance subnetwork contained many of the same OTUs found to be differentially abundant in FMT-recipients, and the abundance of this module was increased in FMT-recipients at discharge and 30 days, compared to sham-treated controls. We conclude in this small pilot study FMT did not have any clinical benefit. A single FMT procedure has the potential to increase bacterial communities of SCFA-producing genera important for intestinal health up to 30 days post-FMT.

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The Effectiveness of Multi-Session FMT Treatment in Active Ulcerative Colitis Patients: A Pilot Study

Biomedicines ◽

10.3390/biomedicines8080268 ◽

2020 ◽

Vol 8 (8) ◽

pp. 268 ◽

Cited By ~ 1

Author(s):

Dorota Mańkowska-Wierzbicka ◽

Marta Stelmach-Mardas ◽

Marcin Gabryel ◽

Hanna Tomczak ◽

Marzena Skrzypczak-Zielińska ◽

...

Keyword(s):

Ulcerative Colitis ◽

Pilot Study ◽

Fecal Microbiota Transplantation ◽

Therapeutic Option ◽

Fecal Microbiota ◽

Metagenomic Analysis ◽

Rrna Gene ◽

Active Ulcerative Colitis ◽

Reactive Protein ◽

Healthy Donors

The modification of the microbiome through fecal microbiota transplantation (FMT) is becoming a very promising therapeutic option for inflammatory bowel disease (IBD) patients. Our pilot study aimed to assess the effectiveness of multi-session FMT treatment in active ulcerative colitis (UC) patients. Ten patients with UC were treated with multi-session FMT (200 mL) from healthy donors, via colonoscopy/gastroscopy. Patients were evaluated as follows: at baseline, at week 7, and after 6 months, routine blood tests (including C reactive protein (CRP) and calprotectin) were performed. 16S rRNA gene (V3V4) sequencing was used for metagenomic analysis. The severity of UC was classified based on the Truelove–Witts index. The assessment of microbial diversity showed significant differences between recipients and healthy donors. FMT contributed to long-term, significant clinical and biochemical improvement. Metagenomic analysis revealed an increase in the amount of Lactobacillaceaea, Micrococcaceae, Prevotellaceae, and TM7 phylumsp.oral clone EW055 during FMT, whereas Staphylococcaceae and Bacillaceae declined significantly. A positive increase in the proportion of the genera Bifidobacterium, Lactobacillus, Rothia, Streptococcus, and Veillonella and a decrease in Bacillus, Bacteroides, and Staphylococcus were observed based on the correlation between calprotectin and Bacillus and Staphylococcus; ferritin and Lactobacillus, Veillonella, and Bifidobacterium abundance was indicated. A positive change in the abundance of Firmicutes was observed during FMT and after 6 months. The application of multi-session FMT led to the restoration of recipients’ microbiota and resulted in the remission of patients with active UC.

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Applying fecal microbiota transplantation (FMT) to treat recurrent Clostridium difficile infections (rCDI) in children

PeerJ ◽

10.7717/peerj.4663 ◽

2018 ◽

Vol 6 ◽

pp. e4663 ◽

Cited By ~ 6

Author(s):

Shaaz Fareed ◽

Neha Sarode ◽

Frank J. Stewart ◽

Aneeq Malik ◽

Elham Laghaie ◽

...

Keyword(s):

Clostridium Difficile ◽

Adverse Effects ◽

Gut Microbiome ◽

Pediatric Patients ◽

Fecal Microbiota Transplantation ◽

Diversity Index ◽

Microbial Community Composition ◽

Fecal Microbiota ◽

Rrna Gene ◽

Significant Difference

Background Fecal Microbiota Transplantation (FMT) is an innovative means of treating recurrent Clostridium difficile infection (rCDI), through restoration of gut floral balance. However, there is a lack of data concerning the efficacy of FMT and its impact on the gut microbiome among pediatric patients. This study analyzes clinical outcomes and microbial community composition among 15 pediatric patients treated for rCDI via FMT. Methods This is a prospective, observational, pilot study of 15 children ≤18 years, who presented for rCDI and who met inclusion criteria for FMT at a pediatric hospital and pediatric gastroenterology clinic. Past medical history and demographics were recorded at enrollment and subsequent follow-up. Specimens of the donors’ and the patients’ pre-FMT and post-FMT fecal specimen were collected and used to assess microbiome composition via 16S rRNA gene sequencing. Results FMT successfully prevented rCDI episodes for minimum of 3 months post-FMT in all patients, with no major adverse effects. Three patients reported continued GI bleeding; however, all three also had underlying Inflammatory Bowel Disease (IBD). Our analyses confirm a significant difference between pre-and post-FMT gut microbiome profiles (Shannon diversity index), whereas no significant difference was observed between post-FMT and donor microbiome profiles. At the phyla level, post-FMT profiles showed significantly increased levels of Bacteroidetes and significantly decreased levels of Proteobacteria. Subjects with underlying IBD showed no difference in their pre-and post-FMT profiles. Conclusion The low rate of recurrence or re-infection by C. difficile, coupled with minimal adverse effects post-FMT, suggests that FMT is a viable therapeutic means to treat pediatric rCDI. Post-FMT microbiomes are different from pre-FMT microbiomes, and similar to those of healthy donors, suggesting successful establishment of a healthier microbiome.

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Lyophilized Fecal Microbiota Transplantation Capsules for Recurrent Clostridium difficile Infection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.943 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S381-S381

Author(s):

Hebert Dupont ◽

Zhi-Dong Jiang ◽

Ashley Alexander ◽

Nadim Ajami ◽

Joseph F Petrosino ◽

...

Keyword(s):

Oral Delivery ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Gene Profiling ◽

Intestinal Microbiome ◽

Published Data ◽

Rrna Gene ◽

Second Phase ◽

Microbiome Diversity

Abstract Background Fecal microbiota (FM) transplantation (FMT) is a highly effective treatment of recurrent C. difficile infection (rCDI). We have published data showing efficacy of fresh, frozen and lyophilized donor microbiota administered by colonoscopy. Most groups are moving toward use of frozen product given by enema and in evaluating encapsulated product for oral delivery. Methods This was a prospective, randomized study of subjects with rCDI (≥ 3 episodes) treated with encapsulated lyophilized FM 100 g given once or 100 g given on two successive days (total 200 g) vs. frozen FM product 100 g given by single retention enema, between March 2015 and February 2017. The clinical outcome was absence of CDI during the 60 days after FMT. The subjects were followed for 6 months for safety. In a subset recipients, microbiome composition by 16S rRNA gene profiling were analyzed on stools obtained pre- and day 2, 7, 14, 30, 60 and 90 days after FMT. Results A total of 54 subjects were enrolled (37/54; 69% female) with a median age of 71 years (range: 20–97). In the first 14 subjects treated, cure rates for oral capsules 100 g FM was 5/8 (63%) vs. 6/6 (100%) for those receiving 100 g frozen FM by enema (P = 0.209). In the second phase of the study cure rate for oral capsules 200 g FM was 17/18 (91%) vs. 20/21 (94%) for the subjects treated by enema by 100 g of frozen product (P = 0.782). No side effects were felt to be related to the procedure or the FMT products were recorded during 6 months follow-up. Two subjects died during follow-up between 3 and 6 months after study due to underlying medical conditions felt to be unrelated to FMT. Microbiota analysis were performed on 40 subjects of which 19/40 (48%) had received capsules. Figure showed that restoration of the intestinal microbiome diversity and Taxa began apparent by 2 days after FMT in both groups and resembled the donor product by 2 weeks with stabilization of the microbiota diversity and Taxa persisting for the 90 days of observation. Conclusion Administration of encapsulated, lyophilized FM resulted in durable restoration of intestinal microbiome diversity comparable to results seen with frozen product given by enema. Disclosures All authors: No reported disclosures.

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Serial Microbiota Analysis after Fecal Microbiota Transplantation in a Child with Down's Syndrome

Journal of Pediatric Infectious Diseases ◽

10.1055/s-0037-1606330 ◽

2017 ◽

Vol 14 (03) ◽

pp. 136-139

Author(s):

Lisethe Meijer ◽

Clementien Vermont ◽

Andries Budding ◽

Chris Mulder ◽

Tim Meij ◽

...

Keyword(s):

Fecal Microbiota Transplantation ◽

Diversity Index ◽

Down's Syndrome ◽

Down’S Syndrome ◽

Fecal Microbiota ◽

Recurrent Clostridium Difficile Infection ◽

Microbiota Analysis ◽

Before And After ◽

Immunocompromised State ◽

Over Time

AbstractFecal microbiota transplantation (FMT) is a very effective treatment for recurrent Clostridium difficile infection (CDI) in adults. However, there is a paucity of data on FMT in children and associated microbiome changes in this particular group. We describe a child with Down's syndrome and intracranial malignancy, who received FMT for recurrent CDI. Detailed microbiota analysis before and after FMT, and pre- and post-recurrence, linked to microbial communities in the donor feces showed that the patient developed a unique microbiota profile after FMT which was very stable over time despite CDI recurrence and subsequent fidaxomicin therapy. Bacteroidetes were stably acquired from donor feces, while Firmicutes, Actinobacteria, Fusobacteria, Verrucomicrobia, and Proteobacteria were unique to the patient. The diversity of microbiota of the patient increased from a Shannon diversity index of 2.08 pre-FMT to 3.12 post-FMT. Our findings underscore that patients with Down's syndrome may well tolerate and benefit from FMT even in a severely immunocompromised state.

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Effects of fecal microbiota transplantation on serum uric acid levels, symptoms and intestinal barrier function in patients with acute and recurrent gout: a pilot study

10.21203/rs.3.rs-41655/v1 ◽

2020 ◽

Author(s):

Wenrui Xie ◽

Xiaoya Yang ◽

Zhihe Deng ◽

Yamei Zheng ◽

Ran Zhang ◽

...

Keyword(s):

Uric Acid ◽

Lactic Acid ◽

Pilot Study ◽

Serum Uric Acid ◽

Barrier Function ◽

Fecal Microbiota Transplantation ◽

Intestinal Barrier ◽

Fecal Microbiota ◽

Intestinal Barrier Function ◽

Acute Gout

Abstract Background: Gut dysbiosis has been reported to be closely associated with gout. Fecal microbiota transplantation (FMT) has been considered as an effective way to restore the balance of gut microbiota. We aimed to evaluate the effects of FMT on serum uric acid levels, gout symptoms and the intestinal barrier function in patients with acute and recurrent gout. Methods: We performed a pilot study of FMT for acute and recurrent gout. The primary outcome was the changes in serum uric acid level on day 28 post-FMT and in gout symptoms by one year. The secondary outcomes included the changes in levels of urine uric acid, diamine oxidase (DAO), D-lactic acid and endotoxin on day 28 post-FMT. The levels of DAO, D-lactic acid and endotoxin were assessed by enzyme assay. Results: Eleven patients received FMT treatment. All the patients had a reduction in serum uric acid levels after FMT treatment ( P < 0.05), accompanied with a decrease in the frequency and duration time of acute gout flares. The levels of DAO, D-lactic acid and endotoxin, reflecting the intestinal barrier function, were higher in patients with gout than in healthy donors ( P < 0.05). After FMT treatment, the levels of DAO and endotoxin decreased ( P < 0.05). Conclusions: Our findings demonstrate that FMT is effective for reducing serum uric acid levels and improving gout symptoms in patients with gout; FMT contributes to improve the impaired intestinal barrier function of the patients.

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Identification and engraftment of new bacterial strains by shotgun metagenomic sequence analysis in patients with recurrent Clostridioides difficile infection before and after fecal microbiota transplantation and in healthy human subjects

PLoS ONE ◽

10.1371/journal.pone.0251590 ◽

2021 ◽

Vol 16 (7) ◽

pp. e0251590

Author(s):

Sandeep Verma ◽

Sudhir K. Dutta ◽

Elad Firnberg ◽

Laila Phillips ◽

Rakesh Vinayek ◽

...

Keyword(s):

Relative Abundance ◽

Fecal Microbiota Transplantation ◽

Bacterial Species ◽

Fecal Microbiota ◽

Metagenomic Sequencing ◽

Bacterial Strains ◽

Metagenomic Sequence ◽

Clostridioides Difficile ◽

Healthy Donors ◽

Before And After

Background Recurrent Clostridioides diffícile infection (RCDI) is associated with major bacterial dysbiosis and colitis. Fecal microbiota transplantation (FMT) is a highly effective therapeutic modality for RCDI. While several studies have identified bacterial species associated with resolution of symptoms in patients, characterization of the fecal microbiome at the bacterial strain level in RCDI patients before and after FMT and healthy donors, has been lacking. The aim of this study was to examine the ability of bacterial strains from healthy donors to engraft in the gastrointestinal tract of patients with RCDI following FMT. Methods Fecal samples were collected from 22 patients with RCDI before and after FMT and their corresponding healthy donors. Total DNA was extracted from each sample and analyzed by shotgun metagenomic sequencing. The Cosmos-ID analysis platform was used for taxonomic assignment of sequences and calculation of the relative abundance (RA) of bacterial species and strains. From these data, the total number of bacterial strains (BSI), Shannon diversity index, dysbiosis index (DI), and bacterial engraftment factor, were calculated for each strain. Findings A marked reduction (p<0·0001) in the RA of total and specific bacterial strains, especially from phylum Firmicutes, was observed in RCDI patients prior to FMT. This change was associated with an increase in the DI (p<0·0001) and in pathobiont bacterial strains from phylum Proteobacteria, such as Escherichia coli O157:H7 and Klebsiella pneumoniae UCI 34. BSI was significantly lower in this group of patients as compared to healthy donors and correlated with the Shannon Index. (p<0·0001). Identification and engraftment of bacterial strains from healthy donors revealed a greater diversity and higher relative abundance of short-chain fatty acid (SCFA)-producing bacterial strains, including Lachnospiraceae bacterium 5_1_63FAA_u_t, Dorea formicigenerans ATCC 27755, Anaerostipes hadrusand others, in RCDI patients after FMT. Interpretation These observations identify a group of SCFA-producing bacterial strains from healthy donors that engraft well in patients with RCDI following FMT and are associated with complete resolution of clinical symptoms and bacterial dysbiosis.

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Fecal filtrate transplantation protects against necrotizing enterocolitis

The ISME Journal ◽

10.1038/s41396-021-01107-5 ◽

2021 ◽

Author(s):

Anders Brunse ◽

Ling Deng ◽

Xiaoyu Pan ◽

Yan Hui ◽

Josué L. Castro-Mejía ◽

...

Keyword(s):

Preterm Infants ◽

Necrotizing Enterocolitis ◽

Fecal Microbiota Transplantation ◽

Gastrointestinal Disorder ◽

Preventive Therapy ◽

Fecal Microbiota ◽

Rrna Gene ◽

Ileal Mucosa ◽

Relevant Animal Model ◽

Life Threatening

AbstractNecrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disorder afflicting preterm infants, which is currently unpreventable. Fecal microbiota transplantation (FMT) is a promising preventive therapy, but the transfer of pathogenic microbes or toxic compounds raise concern. Removal of bacteria from donor feces by micropore filtering may reduce this risk of bacterial infection, while residual bacteriophages could maintain the NEC-preventive effects. We aimed to assess preclinical efficacy and safety of fecal filtrate transplantation (FFT). Using fecal material from healthy suckling piglets, we compared rectal FMT administration (FMT, n = 16) with cognate FFT by either rectal (FFTr, n = 14) or oro-gastric administration (FFTo, n = 13) and saline (CON, n = 16) in preterm, cesarean-delivered piglets as models for preterm infants. We assessed gut pathology and analyzed mucosal and luminal bacterial and viral composition using 16S rRNA gene amplicon and meta-virome sequencing. Finally, we used isolated ileal mucosa, coupled with RNA-Seq, to gauge the host response to the different treatments. Oro-gastric FFT completely prevented NEC, which was confirmed by microscopy, whereas FMT did not perform better than control. Oro-gastric FFT increased viral diversity and reduced Proteobacteria relative abundance in the ileal mucosa relative to control. An induction of mucosal immunity was observed in response to FMT but not FFT. As preterm infants are extremely vulnerable to infections, rational NEC-preventive strategies need incontestable safety profiles. We show in a clinically relevant animal model that FFT, as opposed to FMT, efficiently prevents NEC without any recognizable side effects.

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Human Transmission of Blastocystis by Fecal Microbiota Transplantation Without Development of Gastrointestinal Symptoms in Recipients

Clinical Infectious Diseases ◽

10.1093/cid/ciz1122 ◽

2019 ◽

Vol 71 (10) ◽

pp. 2630-2636 ◽

Cited By ~ 7

Author(s):

Elisabeth M Terveer ◽

Tom van Gool ◽

Rogier E Ooijevaar ◽

Ingrid M J G Sanders ◽

Eline Boeije-Koppenol ◽

...

Keyword(s):

Success Rate ◽

Fecal Microbiota Transplantation ◽

Gastrointestinal Symptoms ◽

Fecal Microbiota ◽

Exclusion Criterion ◽

Chain Reactions ◽

Polymerase Chain Reactions ◽

Clostridioides Difficile ◽

Healthy Donors ◽

Blastocystis Sp

Abstract Background Patients with multiple recurrent Clostridioides difficile infections (rCDI) are treated with fecal microbiota transplantation (FMT), using feces provided by healthy donors. Blastocystis colonization of donors is considered an exclusion criterion, whereas its pathogenicity is still under debate. Methods The introduction of molecular screening for Blastocystis sp. at our stool bank identified 2 donors with prior negative microscopies but positive polymerase chain reactions (PCRs). Potential transmission of Blastocystis sp. to patients was assessed on 16 fecal patient samples, pre- and post-FMT, by PCR and subtype (ST) analyses. In addition, clinical outcomes for the treatment of rCDI (n = 31), as well as the development of gastrointestinal symptoms, were assessed. Results There was 1 donor who carried Blastocystis ST1, and the other contained ST3. All patients tested negative for Blastocystis prior to FMT. With a median diagnosis at 20.5 days after FMT, 8 of 16 (50%) patients developed intestinal colonization with Blastocystis, with identical ST sequences as their respective donors. Blastocystis-containing fecal suspensions were used to treat 31 rCDI patients, with an FMT success rate of 84%. This success rate was not statistically different from patients transferred with Blastocystis sp.–negative donor feces (93%, 76/82). Patients transferred with Blastocystis sp.–positive donor feces did not report any significant differences in bowel complaints in the first week, after 3 weeks, or in the months following FMT. Conclusions We demonstrated the first transmission of Blastocystis ST1 and ST3 from donors to patients by FMT. This did not result in gastrointestinal symptomatology or have any significant effect on rCDI treatment outcomes.

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