| 1. |
- Andréasson, Kristofer, et al.
(author)
-
Treatment for Rheumatoid Arthritis Associated With Alterations in the Gastrointestinal Microbiota
- 2024
-
In: ACR Open Rheumatology. - 2578-5745.
-
Journal article (peer-reviewed)abstract
- Objective: Emerging research suggests that rheumatoid arthritis (RA) is associated with intestinal dysbiosis. This prospective pilot study evaluates changes in intestinal microbial composition in patients with RA initiating treatment with either methotrexate (MTX) or a tumor necrosis factor inhibitor (TNFi). Methods: Consecutive patients, fulfilling the 2010 American College of Rheumatology/EULAR classification criteria for RA, who started treatment with either MTX or TNFi delivered a stool sample upon initiation of immunosuppression and 3 months later. A 16S ribosomal RNA gene-based validated microbiota test (GA-map Dysbiosis Index Score [DIS], Genetic Analysis, Oslo, Norway) was used to evaluate for the presence and degree of dysbiosis. Fecal levels of Prevotella copri (P. copri) were analyzed by custom-made quantitative polymerase chain reaction. Changes in microbial composition were analyzed in relation to changes in disease activity, as measured by the disease activity score based on 28-joint counts, using C-reactive protein. Results: At baseline, dysbiosis was present in 33 of 50 (66%) participants and more common in participants with more than 2 years of disease duration (P = 0.019). At the 3-month follow-up, 27 of 50 (54%) were good treatment responders and the DIS had improved in 14 of 50 (28%). Participants initiating TNFi more often exhibited improvement in the DIS compared with those initiating MTX (P = 0.031). P. copri was identified in 32 of 50 (64%) at baseline. An improvement in disease activity score based on 28-joint counts, using C-reactive protein was associated with a simultaneous decrease in P. copri abundance (rs = 0.30, P = 0.036). Conclusion: This study affirms that dysbiosis is a feature of RA. Although patients were not randomized to MTX or TNFi, the findings suggest that specific therapies may differentially modulate the gastrointestinal microbiota in RA. The association between P. copri and treatment response requires further study.
|
|
| 2. |
- Halkjær, Sofie Ingdam, et al.
(author)
-
Fecal microbiota transplantation for the treatment of irritable bowel syndrome : A systematic review and meta-analysis
- 2023
-
In: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 29:20, s. 3185-3202
-
Research review (peer-reviewed)abstract
- BACKGROUND; Irritable bowel syndrome (IBS) is the most prevalent gastrointestinal disorder in developed countries and reduces patients’ quality of life, hinders their ability to work, and increases health care costs. A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS, also known as ‘gut dysbiosis’. Fecal microbiota transplantation (FMT) has been suggested as a treatment for IBS.AIM: To assess the efficacy and safety of FMT for the treatment of IBS.METHODS: We searched Cochrane Central, MEDLINE, EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials (RCTs) investigating the effectiveness of FMT compared to placebo (including autologous FMT) in treating IBS. The primary outcome was the number of patients with improvements of symptoms measured using a validated, global IBS symptoms score. Secondary outcomes were changes in quality-of-life scores, non-serious and serious adverse events. Risk ratios (RR) and corresponding 95%CI were calculated for dichotomous outcomes, as were the mean differences (MD) and 95%CI for continuous outcomes. The Cochrane risk of bias tool was used to assess the quality of the trials. GRADE criteria were used to assess the overall quality of the evidence.RESULTS: Eight RCTs (484 participants) were included in the review. FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo (RR 1.19, 95%CI: 0.68-2.10). Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group (RR 1.17, 95%CI: 0.63-2.15). One serious adverse event occurred in the FMT group and two in the placebo group (RR 0.42, 95%CI: 0.07-2.60). Endoscopic FMT delivery resulted in a significant improvement in symptoms, while capsules did not. FMT did not improve the quality of life of IBS patients but, instead, appeared to reduce it, albeit non significantly (MD -6.30, 95%CI: -13.39-0.79). The overall quality of the evidence was low due to moderate-high inconsistency, the small number of patients in the studies, and imprecision.CONCLUSION: We found insufficient evidence to support or refute the use of FMT for IBS. Larger trials are needed
|
|
| 3. |
- Holster, Savanne, 1991-, et al.
(author)
-
Allogenic Faecal Microbiota Transfer Induces Immune-Related Gene Sets in the Colon Mucosa of Patients with Irritable Bowel Syndrome
- 2019
-
In: Biomolecules. - : MDPI. - 2218-273X. ; 9:10
-
Journal article (peer-reviewed)abstract
- Faecal microbiota transfer (FMT) consists of the introduction of new microbial communities into the intestine of a patient, with the aim of restoring a disturbed gut microbiota. Even though it is used as a potential treatment for various diseases, it is unknown how the host mucosa responds to FMT. This study aims to investigate the colonic mucosa gene expression response to allogenic (from a donor) or autologous (own) FMT in patients with irritable bowel syndrome (IBS). In a recently conducted randomised, double-blinded, controlled clinical study, 17 IBS patients were treated with FMT by colonoscopy. RNA was isolated from colonic biopsies collected by sigmoidoscopy at baseline, as well as two weeks and eight weeks after FMT. In patients treated with allogenic FMT, predominantly immune response-related gene sets were induced, with the strongest response two weeks after the FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected. Furthermore, several microbiota genera showed correlations with immune-related gene sets, with different correlations found after allogenic compared to autologous FMT. This study shows that the microbe–host response is influenced by FMT on the mucosal gene expression level, and that there are clear differences in response to allogenic compared to autologous FMT.
|
|
| 4. |
|
|
| 5. |
- Holster, Savanne, 1991-
(author)
-
Faecal Microbiota Transfer in Irritable Bowel Syndrome and Collagenous Colitis : Clinical outcomes and host-microbe interactions
- 2020
-
Doctoral thesis (other academic/artistic)abstract
- Faecal microbiota transfer (FMT) aims at restoring a disturbed gut microbiotaby introducing faecal material from a healthy donor into a patient’s intestine. This approach is known as a safe and effective treatment in patients with recurrent Clostridioides difficile infection. This thesis describes the outcomes of two clinical studies in which FMT was investigated as a therapy for irritable bowel syndrome (IBS) patients andin collagenous colitis (CC) patients. Paper I showed that there were no significant differences in IBS symptom scores between patients receiving faecal material from a healthy donor (allogenic FMT) and patients receiving their own faecal material back (autologous FMT). However, unlike autologous FMT, allogenic FMT significantly decreased symptom scores compared to baseline. Additionally, allogenic FMT wasshown to alter the faecal as well as the mucosal microbiota of the IBSpatients. However, also the autologous FMT had an effect on the faecal and mucosal microbiota indicating that the bowel cleansing and/or theprocessing of the autologous faecal material affected the gut microbiota. Paper II showed that the allogenic FMT evoked a clearly different host response in IBS patients than the autologous FMT. Paper III showedthat allogenic FMT did not result in altered faecal metabolite profilesbut in disturbed interactions between the gut microbiota and its metabolites compared to autologous FMT. Paper IV describes the outcomes of the second clinical study in which repeated FMTs resulted inless diarrhoea in a subset of the treated CC patients.Although symptoms improved in both clinical studies, the introduction of a new microbiota by FMT did not seem to be the miracle curefor IBS and CC. However, a subset of patients could benefit from FMT, and a future challenge is to identify this subset. The findings of this thesis are essential for designing further studies aimed at increasing FMT efficacy.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Holster, Savanne, et al.
(author)
-
Faecal microbiota transfer in patients with microscopic colitis : a pilot study in collagenous colitis
- 2020
-
In: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 55:12, s. 1454-1466
-
Journal article (peer-reviewed)abstract
- Objectives: Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of patients with the aim to restore a disturbed gut microbiota. Methods: In this pilot study (NCT03275467), the effect of three repeated FMTs (day 0, two weeks, four weeks) was studied and followed up for six months in nine collagenous colitis (CC) patients, using two stool donors. Results: Five patients had an active disease at the time of baseline sampling. The primary endpoint (remission at six weeks, defined as <3 stools whereof <1 watery stool per day) was achieved by two of these patients, and by one at eight weeks. Overall, in all nine patients, FMT did not result in a significant reduction of watery stools, assessed by daily diary. However, diarrhoea (assessed by gastrointestinal symptom rating scale) was significantly improved at four (p = .038) and eight weeks (p = .038), indigestion at eight (p = .045) and 12 weeks (p = .006), disease-related worries at four (p = .027) and eight weeks (p = .027), and quality of life at six months (p = .009). FMT resulted in an increased number of lamina propria lymphocytes, possibly indicating an initial mucosal immune activation. No serious adverse events, no systemic effects, and no changes in faecal calprotectin and psychological symptoms were observed. Conclusions: FMT is able to improve symptoms in a yet undefined subset of CC patients. Further studies could help to characterise this subset and to understand if these results can be generalised to all microscopic colitis patients.
|
|
| 9. |
|
|
| 10. |
- Holster, Savanne, 1991-, et al.
(author)
-
The Effect of Allogenic Versus Autologous Fecal Microbiota Transfer on Symptoms, Visceral Perception and Fecal and Mucosal Microbiota in Irritable Bowel Syndrome : A Randomized Controlled Study
- 2019
-
In: Clinical and Translational Gastroenterology. - : Nature Publishing Group. - 2155-384X. ; 10:4
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: Fecal microbiota transfer (FMT) is suggested as a potential treatment for patients with irritable bowel syndrome (IBS). We aimed to study the effect of allogenic and autologous FMT on IBS symptoms, visceral sensitivity, and compositional changes in fecal and mucosa-adherent microbiota.METHODS: Seventeen patients with IBS were randomized either to receive fecal material from a healthy donor (allogenic) or to receive their own fecal material (autologous). The fecal material was administered into the cecum by whole colonoscopy after bowel cleansing.RESULTS: No significant differences were found between the allogenic and the autologous FMT regarding symptom scores. However, symptom scores of patients receiving allogenic fecal material significantly decreased after FMT compared with baseline (P 5 0.02), which was not the case in the autologous group (P50.16). Visceral sensitivity was not affected except for a small beneficial effect on urge scores in the autologous group (P < 0.05). While both fecal and mucosa-adherent microbiota of some patients shifted to their respective donor’s fecal microbiota, some patients showed no relevant microbial changes after allogenic FMT. Large compositional shifts in fecal and mucosa-adherent microbiota also occurred in the autologous group.CONCLUSIONS: This study showed that a single FMT by colonoscopy may have beneficial effects in IBS; however, the allogenic fecal material was not superior to the autologous fecal material. This suggests that bowel cleansing prior to the colonoscopy and/or processing of the fecal material as part of the FMT routine contribute to symptoms and gut microbiota composition changes in IBS.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- König, Julia, 1983-, et al.
(author)
-
Randomized clinical trial : Effective gluten degradation by Aspergillus niger-derived enzyme in a complex meal setting
- 2017
-
In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7:13100
-
Journal article (peer-reviewed)abstract
- The Aspergillus niger-derived prolyl endoprotease (AN-PEP) has previously been shown to degrade gluten in healthy subjects when added to an intragastrically infused meal. The current study investigated the efficacy of AN-PEP in a physiological meal setting. In this randomized placebo-controlled crossover study, 18 gluten-sensitive subjects consumed a porridge containing 0.5 g gluten together with two tablets either containing a high or low dose of AN-PEP, or placebo. Gastric and duodenal content was sampled over 180 minutes, and areas under the curve of gluten concentrations were calculated. The primary outcome, i.e. success rate of high dose AN-PEP defined as at least 50% gluten degradation compared to placebo in the duodenum, was achieved in 10 of 13 comparisons. In the stomach, gluten levels were reduced from 176.9 (median, interquartile range 73.5–357.8) to 22.0 (10.6–50.8, p = 0.001) in the high dose and to 25.4 μg × min/ml (16.4–43.7, p = 0.001) in the low dose. In the duodenum, gluten levels were reduced from 14.1 (8.3–124.7) in the placebo to 6.3 (3.5–19.8, p = 0.019) in the high dose and to 7.4 μg × min/ml in the low dose (3.8–12.0, p = 0.015). Thus even in a physiological meal setting, AN-PEP significantly degraded most gluten in the stomach before it entered the duodenum.
|
|
| 14. |
- Marques, Tatiana M., 1980-, et al.
(author)
-
Correlating the gut microbiome to health and disease
- 2016
-
In: The Gut-Brain Axis. - : Elsevier. - 9780128023044 ; , s. 261-291
-
Book chapter (peer-reviewed)abstract
- The gut microbiota is a complex ecosystem consisting of a diverse population of prokaryotes that has a symbiotic relationship with its host; thus it plays a vital role for the host’s health. Our understanding of the effect of the gut microbiome in health and disease has grown substantially over the past 2 decades, mostly because of recent advances in sequencing and other high-throughput technologies. Given its high metabolic potential, close proximity to the intestinal mucosa, and interaction with the immune system, it is not surprising that the gut microbiome is an important partaker in human health. Evidence to the importance of the gut microbiome in human health and disease is the growing number of conditions now linked to changes in the resident gut microbiota, including recurrent Clostridium difficile infections, inflammatory bowel disease, irritable bowel syndrome, colorectal cancer, allergies, neurological diseases, and metabolic diseases. Research into this field of the association of the gut microbiome with health and disease continues to expand at a rapid pace as we come to accept the gut microbiome as our “second genome.” Targeting the gut microbiome to restore/modulate its composition with the use of antibiotics, probiotics, prebiotics, and even fecal microbiota transplantation is considered a promising future strategy for the development of new solutions in the treatment of various diseases associated with an imbalance in microbiota composition and functioning.
|
|
