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Microorganisms
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Impact of Fecal Microbiota Transplantation on Human Health 2.0
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Impact of Fecal Microbiota Transplantation on Human Health 2.0

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Gut Microbiota".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 13987

Special Issue Editors

Dr. Luca Masucci

E-Mail Website
Guest Editor
“Agostino Gemelli” Teaching Hospital, Catholic University of Sacred Heart, 00168 Rome, Italy
Interests: fecal microbiota transplantation; Clostridium infections; microbiota; parasitology
Special Issues, Collections and Topics in MDPI journals
Dr. Gianluca Quaranta

E-Mail Website
Guest Editor
Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Interests: clinical microbiology; gastro-intestinal infections; FMT; parasitology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our previous Special Issue “Impact of Fecal Microbiota Transplantation on Human Health”.

Fecal microbiota transplantation (FMT) consists in the infusion of a feces suspension obtained from a healthy donor into the intestinal tract of a recipient patient. The principle of FMT is the reconstitution of a eubiotic state in an altered intestinal bacterial community or providing potentially protective bacteria against local and systemic pathologies.

Therefore, the restoration of a eubiotic state is not only indicated in intestinal infectious diseases but also in noninfectious diseases. In fact, a normal bacterial community provides protection against an inflammatory status that may have potential systemic effects. Conversely, overexpressed bacterial communities can stimulate inflammatory processes, triggering neurodegenerative disorders such as Parkinson’s disease, amyolateral sclerosis, multiple sclerosis, and autism.

As is evident in the literature, the potential therapeutic options are numerous when considering the capability of FMT to modulate an eventual dysbiotic status, as described in intestinal bowel diseases, cardiovascular diseases, immunity disorders, hepatic encephalopathy, psychiatric conditions, and others.

The aim of this Special Issue is to provide current and thoughtful scientific evidence of the clinical impact of FMT on human health.

Thus, we especially welcome interventional and observational studies aiming to improve the knowledge of FMT’s effects on systemic health and of its use for the treatment of local and systemic diseases. Review studies, including those that use conceptual frameworks for any of the aforementioned topics, will also be welcomed.

Dr. Luca Masucci
Dr. Gianluca Quaranta
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (7 papers)

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Research

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17 pages, 2369 KiB  
Article
Development of a Protocol for Anaerobic Preparation and Banking of Fecal Microbiota Transplantation Material: Evaluation of Bacterial Richness in the Cultivated Fraction
by Berta Bosch, Anna Hartikainen, Aki Ronkainen, Filip Scheperjans, Perttu Arkkila and Reetta Satokari
Microorganisms 2023, 11(12), 2901; https://doi.org/10.3390/microorganisms11122901 - 01 Dec 2023
Cited by 1 | Viewed by 1807
Abstract
Fecal microbiota transplantation (FMT) has shown highly variable results in indications beyond recurrent Clostridioides difficile infection. Microbiota dysbiosis in many diseases is characterized by the depletion of strictly anaerobic bacteria, which may be crucial for FMT efficacy. We developed a protocol to ensure [...] Read more.
Fecal microbiota transplantation (FMT) has shown highly variable results in indications beyond recurrent Clostridioides difficile infection. Microbiota dysbiosis in many diseases is characterized by the depletion of strictly anaerobic bacteria, which may be crucial for FMT efficacy. We developed a protocol to ensure anaerobic conditions during the entire transplant preparation and banking process, from material collection to administration. The protocol necessitates an anaerobic cabinet, i.e., a non-standard laboratory equipment. We analyzed the population of viable anaerobes by combining cultivation and 16S rRNA gene profiling during the transplant preparation, and after 4, 8, and 12 months of anaerobic or aerobic storage at −80 °C, 78% of fecal species were captured via cultivation. Our findings suggest that strictly anaerobic transplant preparation and storage may preserve species richness better than oxic conditions, but the overall difference was not significant. However, specific anaerobes such as Neglecta and Anaerotruncus were affected by the oxygen exposure. A storage time of up to 12 months did not affect the presence of cultivated taxa. Noteworthy, our analysis focused on the richness of cultivated anaerobes rather than their abundance, which may have been affected. The benefits of the developed anaerobic protocol in FMT for specific indications remain to be demonstrated in clinical trials. Full article
(This article belongs to the Special Issue Impact of Fecal Microbiota Transplantation on Human Health 2.0)
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16 pages, 4239 KiB  
Article
Serial Fecal Microbiota Infusions via Colonoscopy for Active Ulcerative Colitis: A Feasibility, Safety, and Translational Monocentric Italian Study
by Loris Riccardo Lopetuso, Lucrezia Laterza, Valentina Petito, Silvia Pecere, Gianluca Quaranta, Federica Del Chierico, Pierluigi Puca, Elisa Schiavoni, Daniele Napolitano, Andrea Poscia, Gianluca Ianiro, Daniela Pugliese, Lorenza Putignani, Maurizio Sanguinetti, Alessandro Armuzzi, Luca Masucci, Antonio Gasbarrini, Giovanni Cammarota and Franco Scaldaferri
Microorganisms 2023, 11(10), 2536; https://doi.org/10.3390/microorganisms11102536 - 11 Oct 2023
Viewed by 977
Abstract
The effectiveness of fecal microbiota transplantation (FMT) in ulcerative colitis (UC) remains unclear. This study aimed to investigate the feasibility and effectiveness of serial fecal infusions via colonoscopy in patients with active UC. Subjects with mild-to-moderate UC received three consecutive fecal infusions via [...] Read more.
The effectiveness of fecal microbiota transplantation (FMT) in ulcerative colitis (UC) remains unclear. This study aimed to investigate the feasibility and effectiveness of serial fecal infusions via colonoscopy in patients with active UC. Subjects with mild-to-moderate UC received three consecutive fecal infusions via colonoscopy. A control population with the same baseline features receiving Infliximab treatment was enrolled. Adverse events and clinical, endoscopic, and microbial outcomes were investigated. Nineteen patients with mildly-to-moderately active UC were enrolled. Clinical response was obtained in six patients at week 2, in eight at week 6, and in nine at week 12. Clinical response was maintained in eight patients at week 24. Endoscopic remission at week 12 was reached in six patients. In the control population, 13/19 patients achieved clinical response at week 6, and 10/19 patients maintained clinical response after 6 months. Microbiota richness was higher in responders compared with the non-responders. Peptostreptococcus, Lactobacillus, and Veillonella were higher in non-responders, while Parabacteroides, Bacteroides, Faecalibacterium, and Akkermansia were higher in responders at all timepoints. Serial FMT infusions appear to be feasible, safe, and effective in UC patients, with a potential role in inducing and maintaining clinical response. Specific bacteria predict the response to FMT. Full article
(This article belongs to the Special Issue Impact of Fecal Microbiota Transplantation on Human Health 2.0)
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15 pages, 1955 KiB  
Article
Anaerobic Feces Processing for Fecal Microbiota Transplantation Improves Viability of Obligate Anaerobes
by Mèlanie V. Bénard, Iñaki Arretxe, Koen Wortelboer, Hermie J. M. Harmsen, Mark Davids, Clara M. A. de Bruijn, Marc A. Benninga, Floor Hugenholtz, Hilde Herrema and Cyriel Y. Ponsioen
Microorganisms 2023, 11(9), 2238; https://doi.org/10.3390/microorganisms11092238 - 05 Sep 2023
Cited by 1 | Viewed by 1402
Abstract
Fecal microbiota transplantation (FMT) is under investigation for several indications, including ulcerative colitis (UC). The clinical success of FMT depends partly on the engraftment of viable bacteria. Because the vast majority of human gut microbiota consists of anaerobes, the currently used aerobic processing [...] Read more.
Fecal microbiota transplantation (FMT) is under investigation for several indications, including ulcerative colitis (UC). The clinical success of FMT depends partly on the engraftment of viable bacteria. Because the vast majority of human gut microbiota consists of anaerobes, the currently used aerobic processing protocols of donor stool may diminish the bacterial viability of transplanted material. This study assessed the effect of four processing techniques for donor stool (i.e., anaerobic and aerobic, both direct processing and after temporary cool storage) on bacterial viability. By combining anaerobic culturing on customized media for anaerobes with 16S rRNA sequencing, we could successfully culture and identify the majority of the bacteria present in raw fecal suspensions. We show that direct anaerobic processing of donor stool is superior to aerobic processing conditions for preserving the bacterial viability of obligate anaerobes and butyrate-producing bacteria related to the clinical response to FMT in ulcerative colitis patients, including Faecalibacterium, Eubacterium hallii, and Blautia. The effect of oxygen exposure during stool processing decreased when the samples were stored long-term. Our results confirm the importance of sample conditioning to preserve the bacterial viability of oxygen-sensitive gut bacteria. Anaerobic processing of donor stool may lead to increased clinical success of FMT, which should further be investigated in clinical trials. Full article
(This article belongs to the Special Issue Impact of Fecal Microbiota Transplantation on Human Health 2.0)
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Review

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14 pages, 1084 KiB  
Review
Microbiota Transplant and Gynecological Disorders: The Bridge between Present and Future Treatments
by Serena Martinelli, Giulia Nannini, Fabio Cianchi, Fabio Staderini, Francesco Coratti and Amedeo Amedei
Microorganisms 2023, 11(10), 2407; https://doi.org/10.3390/microorganisms11102407 - 27 Sep 2023
Cited by 3 | Viewed by 1762
Abstract
Fecal microbiota transplantation (FMT) is a procedure that involves transferring fecal bacteria from a healthy donor to a patients’ intestines to restore gut–immunity homeostasis. While FMT was primarily supposed to treat gastrointestinal disorders such as inflammatory bowel disease and irritable bowel syndrome—and especially [...] Read more.
Fecal microbiota transplantation (FMT) is a procedure that involves transferring fecal bacteria from a healthy donor to a patients’ intestines to restore gut–immunity homeostasis. While FMT was primarily supposed to treat gastrointestinal disorders such as inflammatory bowel disease and irritable bowel syndrome—and especially Clostridium difficile infection (currently the only used as clinical treatment)—recent research has suggested that it may also become a potential treatment for gynecological disorders, including endometriosis and polycystic ovary syndrome (PCOS). On the contrary, vaginal microbiota transplantation (VMT) is a newer and less commonly used procedure than the FMT approach, and its potential applications are still being explored. It involves direct grafting of the entire vaginal microbiota of healthy women into the vaginal tract of patients to easily rebuild the local microbiota environment, restoring vaginal eubiosis and relieving symptoms. Like FMT, VMT is thought to have potential in treating different microbiota-related conditions. In fact, many gynecological disorders, such as bacterial vaginosis and vulvovaginal candidiasis, are thought to be caused by an imbalance in the vaginal microbiota. In this review, we will summarize the development, current challenges, and future perspectives of microbiota transplant, with the aim of exploring new strategies for its employment as a promising avenue for treating a broad range of gynecological diseases. Full article
(This article belongs to the Special Issue Impact of Fecal Microbiota Transplantation on Human Health 2.0)
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20 pages, 1081 KiB  
Review
The Role of Fecal Microbiota Transplantation in the Allogeneic Stem Cell Transplant Setting
by Elisabetta Metafuni, Luca Di Marino, Sabrina Giammarco, Silvia Bellesi, Maria Assunta Limongiello, Federica Sorà, Filippo Frioni, Roberto Maggi, Patrizia Chiusolo and Simona Sica
Microorganisms 2023, 11(9), 2182; https://doi.org/10.3390/microorganisms11092182 - 29 Aug 2023
Cited by 1 | Viewed by 1275
Abstract
Microbiota changes during allogeneic hematopoietic stem cell transplantation has several known causes: conditioning chemotherapy and radiation, broad-spectrum antibiotic administration, modification in nutrition status and diet, and graft-versus-host disease. This article aims to review the current knowledge about the close link between microbiota and [...] Read more.
Microbiota changes during allogeneic hematopoietic stem cell transplantation has several known causes: conditioning chemotherapy and radiation, broad-spectrum antibiotic administration, modification in nutrition status and diet, and graft-versus-host disease. This article aims to review the current knowledge about the close link between microbiota and allogeneic stem cell transplantation setting. The PubMed search engine was used to perform this review. We analyzed data on microbiota dysbiosis related to the above-mentioned affecting factors. We also looked at treatments aimed at modifying gut dysbiosis and applications of fecal microbiota transplantation in the allogeneic stem cell transplant field, with particular interest in fecal microbiota transplantation for graft-versus-host disease (GvHD), multidrug-resistant and clostridium difficile infections, and microbiota restoration after chemotherapy and antibiotic therapy. Full article
(This article belongs to the Special Issue Impact of Fecal Microbiota Transplantation on Human Health 2.0)
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14 pages, 343 KiB  
Review
Migraine as a Disease Associated with Dysbiosis and Possible Therapy with Fecal Microbiota Transplantation
by Ágnes Kappéter, Dávid Sipos, Adorján Varga, Szabolcs Vigvári, Bernadett Halda-Kiss and Zoltán Péterfi
Microorganisms 2023, 11(8), 2083; https://doi.org/10.3390/microorganisms11082083 - 14 Aug 2023
Cited by 7 | Viewed by 3028
Abstract
Migraine is a painful neurological condition characterized by severe pain on one or both sides of the head. It may be linked to changes in the gut microbiota, which are influenced by antibiotic use and other factors. Dysbiosis, which develops and persists as [...] Read more.
Migraine is a painful neurological condition characterized by severe pain on one or both sides of the head. It may be linked to changes in the gut microbiota, which are influenced by antibiotic use and other factors. Dysbiosis, which develops and persists as a result of earlier antibiotic therapy, changes the composition of the intestinal flora, and can lead to the development of various diseases such as metabolic disorders, obesity, hematological malignancies, neurological or behavioral disorders, and migraine. Metabolites produced by the gut microbiome have been shown to influence the gut–brain axis. The use of probiotics as a dietary supplement may reduce the number and severity of migraine episodes. Dietary strategies can affect the course of migraines and are a valuable tool for improving migraine management. With fecal microbiota transplantation, gut microbial restoration is more effective and more durable. Changes after fecal microbiota transplantation were studied in detail, and many data help us to interpret the successful interventions. The microbiological alteration of the gut microflora can lead to normalization of the inflammatory mediators, the serotonin pathway, and influence the frequency and intensity of migraine pain. Full article
(This article belongs to the Special Issue Impact of Fecal Microbiota Transplantation on Human Health 2.0)

Other

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14 pages, 1773 KiB  
Project Report
In Silico Analysis of Changes in Predicted Metabolic Capabilities of Intestinal Microbiota after Fecal Microbial Transplantation for Treatment of Recurrent Clostridioides difficile Infection
by Monica Dahiya, Juan Jovel, Tanya Monaghan, Karen Wong, Wael Elhenawy, Linda Chui, Finlay McAlister and Dina Kao
Microorganisms 2023, 11(4), 1078; https://doi.org/10.3390/microorganisms11041078 - 20 Apr 2023
Viewed by 1459
Abstract
Importance: Although highly effective in treating recurrent Clostridioides difficile infection (RCDI), the mechanisms of action of fecal microbial transplantation (FMT) are not fully understood. Aim: The aim of this study was to explore microbially derived products or pathways that could contribute to the [...] Read more.
Importance: Although highly effective in treating recurrent Clostridioides difficile infection (RCDI), the mechanisms of action of fecal microbial transplantation (FMT) are not fully understood. Aim: The aim of this study was to explore microbially derived products or pathways that could contribute to the therapeutic efficacy of FMT. Methods: Stool shotgun metagenomic sequencing data from 18 FMT-treated RCDI patients at 4 points in time were used for the taxonomic and functional profiling of their gut microbiome. The abundance of the KEGG orthology (KO) groups was subjected to univariate linear mixed models to assess the significance of the observed differences between 0 (pre-FMT), 1, 4, and 12 weeks after FMT. Results: Of the 59,987 KO groups identified by shotgun metagenomic sequencing, 27 demonstrated a statistically significant change after FMT. These KO groups are involved in many cellular processes, including iron homeostasis, glycerol metabolism, and arginine regulation, all of which have been implicated to play important roles in bacterial growth and virulence in addition to modulating the intestinal microbial composition. Conclusion: Our findings suggest potential changes in key KO groups post-FMT, which may contribute to FMT efficacy beyond the restored microbial composition/diversity and metabolism of bile acids and short-chain fatty acids. Future larger studies that include a fecal metabolomics analysis combined with animal model validation work are required to further elucidate the molecular mechanisms. Full article
(This article belongs to the Special Issue Impact of Fecal Microbiota Transplantation on Human Health 2.0)
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