IBD - Inflammatory Bowel Disease (Crohn's, Ulcerative Colitis) and the Microbiome
Summary:
The gut microbiome has been shown to have a major impact on the development, prevention, and treatment of IBD (Crohn's, Ulcerative Colitis). FMTs (Fecal Microbiota Transplants) are being shown to be a likely treatment and prevention for IBD.
Reviews:
Review, 2022: A Systematic Review and Meta-Analysis of Randomized Controlled Trials of Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease https://www.hindawi.com/journals/ecam/2022/8266793/ "Conclusion. FMT is a safe, effective, and well-tolerated therapy. Studies have found that fresh fecal microbiota transplant can increase clinical remission rates"
Gaps in knowledge and future directions for the use of faecal microbiota transplant in the treatment of inflammatory bowel disease (Nov 2019) https://journals.sagepub.com/doi/10.1177/1756284819891038
Recent Research on Fecal Microbiota Transplantation in Inflammatory Bowel Disease Patients (Q&A with Monika Fischer, MD. Gastroenterol Hepatol, Jan 2019) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423689/ | Similar one from 2018 with one of the authors: https://www.gastroenterologyandhepatology.net/archives/may-2018/update-on-fecal-microbiota-transplantation-in-patients-with-inflammatory-bowel-disease/
Review, 2018: The role of fecal microbiota transplantation in inflammatory bowel disease. "Despite high heterogenity in all areas of procedure, overall, this review supports a positive effect of FMT on outcome of IBD and FMT was well tolerated for the majority of patients." https://onlinelibrary.wiley.com/doi/abs/10.1111/1751-2980.12603 | Another 2018 review: Current Evidence for the Management of Inflammatory Bowel Diseases Using Fecal Microbiota Transplantation https://link.springer.com/article/10.1007/s11908-018-0627-8
Review, 2018: Fecal microbiota transplant – a new frontier in inflammatory bowel disease https://doi.org/10.2147/JIR.S176190 "Clinical trials data are still poor but strongly support a future introduction of FMT in therapy to manage IBD microbiome. More studies are needed to assess the optimal route of administration and the frequency of FMT, the best matched donor for each patient as well as the risks associated with FMT in IBD"
Review, 2017: Gut microbiota in the pathogenesis of inflammatory bowel disease: https://link.springer.com/article/10.1007%2Fs12328-017-0813-5
Review, 2016: The association between the gut microbiota and the inflammatory bowel disease activity: a systematic review and meta-analysis: https://www.tandfonline.com/doi/full/10.1080/00365521.2016.1216587
General:
Inflammatory Bowel Disease Outcomes Following Fecal Microbiota Transplantation for Recurrent C. difficile Infection (Nov 2020, n=50, Crohn’s and UC) https://academic.oup.com/ibdjournal/advance-article-abstract/doi/10.1093/ibd/izaa283/5957723 "This prospective trial assessing FMT in IBD-CDI patients suggests IBD outcomes are better than reported in retrospective studies. Among the Crohn’s disease cohort, 73.3% (11 of 15) had IBD improvement. Among the ulcerative colitis cohort, 62% (22 of 34) had IBD improvement."
Fecal microbiota transplantation results in bacterial strain displacement in patients with inflammatory bowel diseases (Oct 2019) https://febs.onlinelibrary.wiley.com/doi/abs/10.1002/2211-5463.12744 "3 days after FMT, 11 out of 15 recipients were in remission"
Microbiotas from Humans with Inflammatory Bowel Disease Alter the Balance of Gut Th17 and RORγt+ Regulatory T Cells and Exacerbate Colitis in Mice (2019): https://doi.org/10.1016/j.immuni.2018.12.015
"In a population-based study, we found infection within the first year of life to be associated with a diagnosis of IBD. This might be due to use of antibiotics or a physiologic defect at a critical age for gut microbiome development." (Feb 2019) https://www.gastrojournal.org/article/S0016-5085(19)30374-9/fulltext
Antibiotics induce remission in children with IBD failing a biologic. Efficacy of Combination Antibiotic Therapy for Refractory Pediatric Inflammatory Bowel Disease (Feb 2019, n=63) https://www.healio.com/gastroenterology/inflammatory-bowel-disease/news/online/%7B72c81723-eb83-4b8d-b835-d554e20459e9%7D/antibiotics-induce-remission-in-children-with-ibd-failing-a-biologic
Metagenomic analysis of intestinal mucosa revealed a specific eukaryotic gut virome signature in early-diagnosed inflammatory bowel disease (2018): https://doi.org/10.1080/19490976.2018.1511664 "findings support the idea that certain eukaryotic viruses might trigger intestinal inflammation and contribute to IBD pathogenesis and pave the way not only for the discovery of novel diagnostic biomarkers but also for the development of anti-viral drugs for the treatment of IBD"
Distinct Microbial Communities Trigger Colitis Development upon Intestinal Barrier Damage via Innate or Adaptive Immune Cells (2017): https://www.cell.com/cell-reports/fulltext/S2211-1247(17)31417-1
Worm infection counters inflammatory bowel disease by drastically changing gut microbiome: https://www.sciencedaily.com/releases/2016/04/160414145513.htm
Breakdown products from microcin B17, a well-known toxin produced by E. coli, seem to trigger gut inflammation that is characteristic of IBD (2018): https://medicalxpress.com/news/2018-05-chance-discovery-links-inflammatory-bowel.html
Crohn's disease:
Foodborne fungus impairs intestinal wound healing in Crohn's disease (Mar 2021) https://medicalxpress.com/news/2021-03-foodborne-fungus-impairs-intestinal-wound.html Debaryomyces is enriched in Crohn’s disease intestinal tissue and impairs healing in mice.
Malassezia (skin fungus) Is Associated with Crohn’s Disease and Exacerbates Colitis in Mouse Models (Mar 2019) https://www.sciencedirect.com/science/article/pii/S1931312819300459 "Collectively, these results suggest that targeting specific commensal fungi may be a therapeutic strategy for IBD"
The fecal microbiota as a biomarker for disease activity in Crohn’s disease (2016): https://www.nature.com/articles/srep35216
A microbial signature for Crohn's disease (2017): https://gut.bmj.com/content/66/5/813
Serologic microbial associated markers can predict Crohn's disease behaviour years before disease diagnosis (2016): https://onlinelibrary.wiley.com/doi/10.1111/apt.13641/abstract
Genetic Variant Newly Linked to Crohn’s Disease Also Associated with Altered Gut Microbiome Composition (2016): https://medicalxpress.com/news/2016-08-genetic-variant-newly-linked-crohn.html A Frameshift in CSF2RB Predominant Among Ashkenazi Jews Increases Risk for Crohn's Disease and Reduces Monocyte Signaling via GM-CSF.
Case Western Reserve-Led International Team Identifies Fungus in Humans for First Time as Key Factor in Crohn’s Disease (2016): https://www.newswise.com/articles/case-western-reserve-led-international-team-identifies-fungus-in-humans-for-first-time-as-key-factor-in-crohn-s-disease
A role for bacterial urease in gut dysbiosis and Crohn’s disease. Bacterial (E. coli) enzyme (urease) reconfigures the entire gut microbiome and worsens immune-mediated colitis: https://www.sciencedaily.com/releases/2017/11/171115144142.htm
FMT for Crohn's disease:
Repeated and multiple fecal microbiota transplantations plus partial enteral nutrition as the first-line treatment in active pediatric Crohn’s disease (Feb 2023, n=25) https://www.frontiersin.org/articles/10.3389/fcimb.2023.1083236/full "At week 18-22, clinical remission was achieved in 72.7% and 20.0% of patients in the FMT and PEN groups". Lower route, no bowel prep, multiple fresh FMTs, 12 donors (relatives and trusted friends) - one donor per recipient.
Multiple fresh fecal microbiota transplants induces and maintains clinical remission in Crohn’s disease complicated with inflammatory mass (2017): https://www.nature.com/articles/s41598-017-04984-z
Fecal microbiota transplantation through mid-gut for refractory Crohn's disease: Safety, feasibility, and efficacy trial results (2014, n=30) https://onlinelibrary.wiley.com/doi/10.1111/jgh.12727 "The rate of clinical improvement and remission based on clinical activity at the first month was 86.7% (26/30) and 76.7% (23/30), respectively. Patients' body weight increased after FMT, and the lipid profile improved as well. FMT also showed a fast and continuous significant effect in relieving the sustaining abdominal pain associated with sustaining CD."
Transplant of microbiota from Crohn’s disease patients to germ-free mice results in colitis (Mar 2024) https://www.tandfonline.com/doi/full/10.1080/19490976.2024.2333483
Ulcerative Colitis:
FMT seems to be more heavily studied in Ulcerative Colitis than in Crohn's disease. "In contrast to UC, the inflammation in Crohn's disease (CD) has much more systemic character and the intestinal damage is much more profound (transmural)."
Review, Sep 2023: Efficacy and safety of fecal microbiota transplantation in the treatment of ulcerative colitis: a systematic review and meta-analysis https://www.nature.com/articles/s41598-023-41182-6
Review, Jun 2022: Efficacy of Fecal Microbiota Transplantation in the Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials https://academic.oup.com/ibdjournal/advance-article-abstract/doi/10.1093/ibd/izac135/6619552 "Clinical remission or response and endoscopic remission or response were significantly higher in patients who received FMT compared with placebo without any differences in serious or specific adverse events."
Review, Jun 2016: Fecal Microbiota Transplantation for Ulcerative Colitis: A Systematic Review and Meta-Analysis: https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0157259
Review, Sep 2017: Systematic Review and Meta-analysis: Fecal Microbiota Transplantation for Treatment of Active Ulcerative Colitis: https://academic.oup.com/ibdjournal/article/23/10/1702/4791645 Pooled rate of clinical remission in all 4 trials was 42.1% in the group receiving donor FMT and 22.6% in those receiving control. | Discussion with one of the authors in 2018: https://www.gastroenterologyandhepatology.net/archives/may-2018/update-on-fecal-microbiota-transplantation-in-patients-with-inflammatory-bowel-disease/
Microbial determinants of effective donors in faecal microbiota transplantation for UC (Jul 2022) https://gut.bmj.com/content/72/1/90 "one donor having 100% efficacy compared with a second donor (36% efficacy). Donor microbiota stability and species evenness were identified as novel metrics that were associated with therapeutic efficacy in UC, beyond individual microbial species or metabolites"
Intestinal Microbiome Changes and Clinical Outcomes of Patients with Ulcerative Colitis after Fecal Microbiota Transplantation (Dec 2023, n=20, 10x enemas, 3 donors) https://www.mdpi.com/2077-0383/12/24/7702 "Clinical remission was achieved in 19 (95%) patients at week 8"
Capsulized Fecal Microbiota Transplantation Induces Remission in Patients with Ulcerative Colitis by Gut Microbial Colonization and Metabolite Regulation (Apr 2023, n=22) https://journals.asm.org/doi/10.1128/spectrum.04152-22 "FMT induced clinical remission and clinical response in 57.1% (12 of 21) and 76.2% (16 of 21) of UC patients"
Fecal microbiota transplantation for recurrent Clostridioides difficile infection in patients with concurrent ulcerative colitis (Apr 2023, n=34) https://www.sciencedirect.com/science/article/abs/pii/S0896841123000422 "Twenty-four patients (69%) experienced remission or an amelioration of UC activity"
"Forty-four eligible patients were included in the analysis. Of them, 50.0% and 29.5% achieved clinical response and clinical remission, respectively, 3 months post-FMT." https://www.mdpi.com/2072-6643/15/15/3340 The Underlying Changes in Serum Metabolic Profiles and Efficacy Prediction in Patients with Extensive Ulcerative Colitis Undergoing Fecal Microbiota Transplantation.
Fecal Microbiota Transplantation Ameliorates Active Ulcerative Colitis by Downregulating Pro-inflammatory Cytokines in Mucosa and Serum (Apr 2022, n=27) https://www.frontiersin.org/articles/10.3389/fmicb.2022.818111/full "16 (59.3%) achieved efficacious clinical response and 11 (40.7%) clinical remission"
Fecal microbiota transplantation versus glucocorticoids for the induction of remission in mild to moderate ulcerative colitis (Aug 2022, n=122) https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03569-3 "FMT therapy was as effective as glucocorticoids to induce remission in active mild to moderate UC, accompanied by fewer adverse events"
Lyophilised oral faecal microbiota transplantation for ulcerative colitis (LOTUS): a randomised, double-blind, placebo-controlled trial (Dec 2021, n=35) https://www.thelancet.com/journals/langas/article/PIIS2468-1253(21)00400-3/fulltext "At week 8, eight (53%) of 15 patients in the FMT group were in corticosteroid-free clinical remission with endoscopic remission or response, as were three (15%) of 20 patients in the placebo group"
Efficacy of fecal microbiota therapy in steroid dependent ulcerative colitis: a real world intention-to-treat analysis (Nov 2018, n=345): https://doi.org/10.5217/ir.2018.00089
Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients With Ulcerative Colitis. A Randomized Clinical Trial (Jan 2019): https://jamanetwork.com/journals/jama/article-abstract/2720727 "1-week treatment with anaerobically prepared donor FMT compared with autologous FMT resulted in a higher (32% vs 9%) likelihood of remission at 8 weeks."
The taxonomic composition of the donor intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis (2017): https://onlinelibrary.wiley.com/doi/10.1111/apt.14387/abstract
Fecal microbiome from patients with ulcerative colitis is potent to induce inflammatory responses. "fecal bacteria from UC patients cause stronger inflammatory responses than fecal bacteria from healthy controls" (2018): https://www.sciencedirect.com/science/article/pii/S1567576918301589
"FMT from UC donors to normal recipient rats triggered UC symptoms, UC-prone microbial shift, and host metabolic adaption" (2018): https://aem.asm.org/content/early/2018/04/30/AEM.00434-18.abstract
Fecal Transplants Effective (Jun 2016): https://www.sciencedaily.com/releases/2016/05/160523160429.htm | Specific Bacteria and Metabolites Associated With Response to Fecal Microbiota Transplantation in Patients With Ulcerative Colitis (2018, n=81) | Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial (2017, n=85).
Severe form of inflammatory bowel disease linked to a strain of mouth bacteria (Campylobacter concisus) (Oct 2020) https://medicalxpress.com/news/2020-10-severe-inflammatory-bowel-disease-linked.html Analysis of complete Campylobacter concisus genomes identifies genomospecies features, secretion systems and novel plasmids and their association with severe ulcerative colitis.
Microbiome profiling reveals associations with ulcerative colitis severity, treatment. Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course (Oct 2018): https://medicalxpress.com/news/2018-10-microbiome-profiling-reveals-associations-ulcerative.html - https://doi.org/10.1016/j.chom.2018.09.009
Gut mucosal virome alterations in ulcerative colitis (Mar 2019): https://gut.bmj.com/content/early/2019/03/05/gutjnl-2018-318131 "We demonstrated for the first time that UC is characterised by substantial alterations of the mucosa virobiota with functional distortion. Enrichment of Caudovirales bacteriophages, increased phage/bacteria virulence functions and loss of viral-bacterial correlations in the UC mucosa highlight that mucosal virome may play an important role in UC pathogenesis"