scholarly journals High engraftment capacity of frozen ready-to-use human fecal microbiota transplants assessed in germ-free mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Magali Berland ◽  
Julie Cadiou ◽  
Florence Levenez ◽  
Nathalie Galleron ◽  
Benoît Quinquis ◽  
...  
Keyword(s):  
Mouse Model ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Fecal Microbiota Transplant ◽  
Shotgun Metagenomics ◽  
Germ Free ◽  
Important Group ◽  
Freeze Dried ◽  
The Family ◽  
Fresh Preparation

AbstractThe number of indications for fecal microbiota transplantation is expected to rise, thus increasing the needs for production of readily available frozen or freeze-dried transplants. Using shotgun metagenomics, we investigated the capacity of two novel human fecal microbiota transplants prepared in maltodextrin-trehalose solutions (abbreviated MD and TR for maltodextrin:trehalose, 3:1, w/w, and trehalose:maltodextrin 3:1, w/w, respectively), to colonize a germ-free born mouse model. Gavage with frozen-thawed MD or TR suspensions gave the taxonomic profiles of mouse feces that best resembled those obtained with the fresh inoculum (Spearman correlations based on relative abundances of metagenomic species around 0.80 and 0.75 for MD and TR respectively), while engraftment capacity of defrosted NaCl transplants most diverged (Spearman correlations around 0.63). Engraftment of members of the family Lachnospiraceae and Ruminoccocaceae was the most challenging in all groups of mice, being improved with MD and TR transplants compared to NaCl, but still lower than with the fresh preparation. Improvement of engraftment of this important group in maintaining health represents a challenge that could benefit from further research on fecal microbiota transplant manufacturing.

scholarly journals Consistent alterations of human fecal microbes after transplanted to germ-free mice

2018 ◽  
Author(s):  
Yanze Li ◽  
Wenming Cao ◽  
Na L Gao ◽  
Xing-Ming Zhao ◽  
Wei-Hua Chen
Keyword(s):  
Mouse Model ◽  
Gut Microbiota ◽  
Fecal Microbiota ◽  
Species Level ◽  
Human Gut ◽  
Fecal Microbiota Transplant ◽  
Change Rate ◽  
Gut Microbes ◽  
Germ Free ◽  
Human And Mouse

AbstractBackgroundFecal microbiota transplant (FMT) of human fecal samples to germ-free (GF) mice is useful for establishing causal relationships between gut microbiota and human phenotypes. However, due to intrinsic differences between human and mouse intestines and distinct diets between the two organisms, replicating human phenotypes in mouse through FMT is not guaranteed; similarly, treatments that are effective in mouse models do not guarantee their success in human either.ResultsIn this study, we aimed to identify human gut microbes that have undergone significant and consistent changes after transplanted to GF mice across multiple experimental settings. By comparing gut microbiota profiles in 1,713 human-mouse pairs, we found strikingly on average <50% of the human gut microbes can be re-established in mice at the species level; among which, more than 1/3 have undergone significant changes (referred as to “variable microbes”), most of which were consistent across multiple human-mouse pairs and experimental settings. Consistently, one-third of human samples had changed their enterotypes, i.e. significant changes in their leading species after FMT. Mice fed with controlled diet showed significant decrease in the enterotype change rate (~25%) as compared those with non-controlled diet (~50%), suggesting a possible solution for rescue. Strikingly, most of the variable microbes have been implicated in human diseases, with some being recognized as causing species.ConclusionsOur results highlighted the challenges of using mouse model in replicating human gut microbiota-associated phenotypes, provided useful information for researchers using mice in their gut microbiota studies and call for additional validations after FMT.

scholarly journals Fecal Microbiota Transplant in Two Ulcerative Colitis Pediatric Cases: Gut Microbiota and Clinical Course Correlations

2020 ◽  
Vol 8 (10) ◽  
pp. 1486
Author(s):  
Andrea Quagliariello ◽  
Federica Del Chierico ◽  
Sofia Reddel ◽  
Alessandra Russo ◽  
Andrea Onetti Muda ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Clinical Effects ◽  
Phylogenetic Distance ◽  
Fecal Microbiota Transplant ◽  
Inflammatory Bowel ◽  
Clinical Conditions ◽  
And Control

Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- and post-FMT monitored for clinical conditions and gut bacterial ecology. Microbiota profiling relied on receipts’ time-point profiles, donors and control cohorts’ baseline descriptions. After FMT, the improvement of clinical conditions was recorded for both patients. After 12 months, the mild UC patient was in clinical remission, while the moderate UC patient, after 12 weeks, had a clinical worsening. Ecological analyses highlighted an increase in microbiota richness and phylogenetic distance after FMT. This increase was mainly due to Collinsella aerofaciens and Eubacterium biforme, inherited by respective donors. Moreover, a decrease of Proteus and Blautia producta, and the increment of Parabacteroides, Mogibacteriaceae, Bacteroides eggerthi, Bacteroides plebeius, Ruminococcus bromii, and BBacteroidesovatus were associated with remission of the patient’s condition. FMT results in a long-term response in mild UC, while in the moderate form there is probably need for multiple FMT administrations. FMT leads to a decrease in potential pathogens and an increase in microorganisms correlated to remission status.

scholarly journals A Systematic Review of the Efficacy and Safety of Fecal Microbiota Transplant for Clostridium difficile Infection in Immunocompromised Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Oluwaseun Shogbesan ◽  
Dilli Ram Poudel ◽  
Samjeris Victor ◽  
Asad Jehangir ◽  
Opeyemi Fadahunsi ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
English Language ◽  
Fecal Microbiota Transplantation ◽  
Secondary Infection ◽  
Organ Transplant ◽  
Fecal Microbiota ◽  
Immunocompromised Patients ◽  
Serious Adverse Events ◽  
Fecal Microbiota Transplant ◽  
Immunosuppressant Medications

Background. Fecal microbiota transplantation (FMT) has been shown to be effective in recurrent Clostridium difficile (CD) infection, with resolution in 80% to 90% of patients. However, immunosuppressed patients were often excluded from FMT trials, so safety and efficacy in this population are unknown. Methods. We searched MEDLINE and EMBASE for English language articles published on FMT for treatment of CD infection in immunocompromised patients (including patients on immunosuppressant medications, patients with human immunodeficiency virus (HIV), inherited or primary immunodeficiency syndromes, cancer undergoing chemotherapy, or organ transplant, including-bone marrow transplant) of all ages. We excluded inflammatory bowel disease patients that were not on immunosuppressant medications. Resolution and adverse event rates (including secondary infection, rehospitalization, and death) were calculated. Results. Forty-four studies were included, none of which were randomized designs. A total of 303 immunocompromised patients were studied. Mean patient age was 57.3 years. Immunosuppressant medication use was the reason for the immunocompromised state in the majority (77.2%), and 19.2% had greater than one immunocompromising condition. Seventy-six percent were given FMT via colonoscopy. Of the 234 patients with reported follow-up outcomes, 207/234 (87%) reported resolution after first treatment, with 93% noting success after multiple treatments. There were 2 reported deaths, 2 colectomies, 5 treatment-related infections, and 10 subsequent hospitalizations. Conclusion. We found evidence that supports the use of FMT for treatment of CD infection in immunocompromised patients, with similar rates of serious adverse events to immunocompetent patients.

scholarly journals Lupus Gut Microbiota Transplants Cause Autoimmunity and Inflammation

2021 ◽  
Author(s):  
Yiyangzi Ma ◽  
Ruru Guo ◽  
Yiduo Sun ◽  
Xin Li ◽  
Lun He ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Lupus Erythematosus ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Healthy Controls ◽  
Germ Free ◽  
Autoimmune Antibodies ◽  
Expression Of Genes ◽  
Rdna Sequencing

Background: The etiology of systemic lupus erythematosus (SLE) is multifactorial. Recently, growing evidence suggests that the microbiota plays a role in SLE, yet whether gut microbiota participates in the development of SLE remains largely unknown. To investigate this issue, we carried out 16s rDNA sequencing analyses in a cohort of 18 female un-treated active SLE patients and 7 female healthy controls, and performed fecal microbiota transplantation from patients and healthy controls to germ-free mice. Results: Compared to the healthy controls, we found no significant different microbial diversity but some significantly different species in SLE patients including Turicibacter genus and other 5 species. Fecal transfer from SLE patients to germ free (GF) C57BL/6 mice caused GF mice to develop a series of lupus-like phenotyptic features, which including an increased serum autoimmune antibodies, and imbalanced cytokines, altered distribution of immune cells in mucosal and peripheral immune response, and upregulated expression of genes related to SLE in recipient mice that received SLE fecal microbiota transplantation (FMT). Moreover, the metabolism of histidine was significantly altered in GF mice treated with SLE patient feces, as compared to those which received healthy fecal transplants. Conclusions: Overall, our results describe a causal role of aberrant gut microbiota in contributing to the pathogenesis of SLE. The interplay of gut microbial and histidine metabolism may be one of the mechanisms intertwined with autoimmune activation in SLE.

Fecal Microbiota Transplantation Donor Screening Updates and Research Gaps for Solid Organ Transplant Recipients

2021 ◽  
Author(s):  
Nirja Mehta ◽  
Tiffany Wang ◽  
Rachel J. Friedman-Moraco ◽  
Cynthia Carpentieri ◽  
Aneesh K. Mehta ◽  
...  
Keyword(s):  
Opportunistic Infections ◽  
Fecal Microbiota Transplantation ◽  
Organ Transplant ◽  
Fecal Microbiota ◽  
Solid Organ Transplant ◽  
Pathogen Transmission ◽  
Solid Organ ◽  
Fecal Microbiota Transplant ◽  
Donor Screening ◽  
Clostridioides Difficile

In this review, we discuss stool donor screening considerations to mitigate potential risks of pathogen transmission through fecal microbiota transplant (FMT) in solid organ transplant (SOT) recipients. SOT recipients have a higher risk for Clostridioides difficile infection (CDI) and are more likely to have severe CDI. FMT has been shown to be a valuable tool in the treatment of recurrent CDI (RCDI), however guidelines for screening for opportunistic infections transmitted through FMT are underdeveloped. We review reported adverse effects of FMT as they pertain to an immunocompromised population and discuss current understanding and recommendations for screening found in the literature while noting gaps in research. We conclude that while FMT is being performed in the SOT population, typically with positive results, there remain many unanswered questions which may have major safety implications and warrant further study.

Non-uinform gut microbiota alteration patterns associated with therapeutic outcomes in an Alzheimer's disease animal model

2019 ◽  
Author(s):  
Min Wang ◽  
William Kwame Amakye ◽  
Jianing Cao ◽  
Congcong Gong ◽  
Xiaoyu Sun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Therapeutic Outcomes ◽  
Targeted Treatments ◽  
Amyloid Aβ

Abstract Background: Dysbiosis of gut microbiota is associated with the progression of beta-amyloid (Aβ) pathology in Alzheimer’s disease (AD). We aimed to identify uniform Aβ-responsible gut microbiota status as possible guideline for gut microbiota manipulation and the prediction of outcomes of microbiota targeted treatments. Six months old APP/PS1 mice from the same genetic background, housing and feeding conditions were then daily gavage with Metformin, peptides WN5 or PW5 to manipulate the gut microbiota for 12 weeks. Aβ pathology and gut microbiota were then explored and compared. Results: Fecal microbiota transplantation (FMT) from a 16 month old APP/PS1 mouse reconstituted the gut microbiota towards the donor and increased Aβ pathology in APP/PS1 mouse model. Metformin, peptides WN5 and PW5 all attenuated Aβ-plaque formation in APP/PS1 mouse model but each was associated with distinct gut microbiota status. No uniform gut microbiota pattern associated with Aβ pathology was found among different gut microbiota-targeted treatments. Conclusion: We found no uniform gut microbiota status associated with Aβ pathology suggesting gut microbiota status is not a suitable biomarker for AD diagnosis and treatment predictions. Alteration of gut microbiota in itself may not be sufficiently directly related to functional outcomes and might only be a shadow of deeper molecular mechanisms not fully understood. The findings here strongly suggested that the significance of gut microbiota alteration in disease pathology and treatment may have so far been over claimed and that interpretation of gut microbiota data should be done with utmost caution.

scholarly journals A118 GUT MICROBIOTA TRANSPLANTATION FROM A PATIENT WITH SEVERE CONSTIPATION INDUCED CHANGES IN COLONIC FUNCTION AND STRUCTUR OF GNOTOBIOTIC MICE

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 137-138
Author(s):  
X Bai ◽  
G De Palma ◽  
J Lu ◽  
S M Collins ◽  
P Bercik
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Colonic Transit ◽  
Slow Transit Constipation ◽  
Antibiotic Exposure ◽  
Ach Release ◽  
Germ Free ◽  
Gi Transit

Abstract Background Increasing evidence suggests that gut microbiota play a key role in gastrointestinal (GI) tract function. We have previously shown that fecal microbiota transplantation diarrhea predominant IBS patients into germ-free mice induces faster GI transit, increased permeability and innate immune activation. However, it is unknown whether gut dysfunction is induced by microbiota from patients with chronic constipation. Aims Here, we investigated the role of the intestinal microbiota in the expression of severe slow transit constipation in a patient with previous C difficile infection and extensive antibiotic exposure. Methods Germ-free (GF) mice (14 weeks old) were gavaged with diluted fecal content from the patient with constipation (PA) or a sex and age-matched healthy control (HC). 12 weeks later, we assessed gut motility and GI transit using videofluoroscopy and a bead expulsion test.. We then investigated intestinal and colonic smooth muscle isometric contraction in vitro using electric field stimulation (EFS), and acetylcholine (Ach) release was assessed by superfusion using [3H] choline. Histological changes were evaluated by H&E and immunohistochemistry. Results Mice with PA microbiota had faster whole GI transit (score 18.9 ± 0.9 (N=9) than mice with HC microbiota (15.4 ± 1.0, N=10, p=0.032), with markers located mainly in the distal small bowel and cecum. However, bead expulsion from the colon was significantly longer in PA mice (420.8 s ± 124.6 s, N=9) than in HC mice (82.6 s ± 20.0 s, N=10, p=0.026). This delayed colonic transit was likely due to colonic retroperistalsis visualized videofluoroscopically by retrograde flow of barium in the right colon of PA mice. There was no difference between the two groups in small intestinal or colonic tissues in Ach release or contractility induced by carbachol or KCl,. EFS caused transient biphasic relaxation and contraction in small intestine and colon, with the colonic contraction being stronger in the PA group. Microscopic tissue analysis showed disruption of the interstitial cells of Cajal (ICC) network and increased lymphocyte infiltration in colonic mucosa and submucosa in PA mice. Conclusions These results indicate that the microbiota is a driver of delayed colonic transit in a patient whose constipation started following extensive antibiotic exposure for C. difficile infection. The observed dysmotility pattern was not due to lower muscle contractility but likely caused by immune mediated changes in the ICC network. Funding Agencies CIHR

scholarly journals Gut Fecal Microbiota Transplant in a Mouse Model of Orthotopic Rectal Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Yen-Cheng Chen ◽  
Zhi-Feng Miao ◽  
Kwan-Ling Yip ◽  
Yi-An Cheng ◽  
Chung-Jung Liu ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Mouse Model ◽  
Fecal Microbiota ◽  
Fecal Microbiota Transplant

scholarly journals Longitudinal dynamics of gut bacteriome, mycobiome and virome after fecal microbiota transplantation in graft-versus-host disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Fen Zhang ◽  
Tao Zuo ◽  
Yun Kit Yeoh ◽  
Frankie W. T. Cheng ◽  
Qin Liu ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Temporal Dynamics ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Cell Transplant ◽  
Fecal Microbiota Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Longitudinal Dynamics ◽  
Graft Versus Host

AbstractFecal microbiota transplant (FMT) has emerged as a potential treatment for severe colitis associated with graft-versus-host disease (GvHD) following hematopoietic stem cell transplant. Bacterial engraftment from FMT donor to recipient has been reported, however the fate of fungi and viruses after FMT remains unclear. Here we report longitudinal dynamics of the gut bacteriome, mycobiome and virome in a teenager with GvHD after receiving four doses of FMT at weekly interval. After serial FMTs, the gut bacteriome, mycobiome and virome of the patient differ from compositions before FMT with variable temporal dynamics. Diversity of the gut bacterial community increases after each FMT. Gut fungal community initially shows expansion of several species followed by a decrease in diversity after multiple FMTs. In contrast, gut virome community varies substantially over time with a stable rise in diversity. The bacterium, Corynebacterium jeikeium, and Torque teno viruses, decrease after FMTs in parallel with an increase in the relative abundance of Caudovirales bacteriophages. Collectively, FMT may simultaneously impact on the various components of the gut microbiome with distinct effects.

Sign in / Sign up

Export Citation Format

Share Document